The observational analysis screened the Danish Multiple Sclerosis Registry for patients with relapsing–remitting multiple sclerosis who had received at least two five-day cladribine treatment cycles and were followed for more than 90 days. From 90 days after the first dose, designated the index point, researchers analysed annualised relapse rates through year three alongside activity measures based on relapses or magnetic resonance imaging activity. They also examined time to the first 24-week confirmed disability worsening, disability progression independent of relapses, and loss of “no evidence of disease activity,” abbreviated NEDA-3.

Predictor analyses considered age, split at 45 years, disease activity before baseline, and short-term NEDA-3 status. Younger age and greater pre-baseline activity were associated with more frequent short-term disease activity. Pre-baseline activity also predicted short-term loss of NEDA-3. These findings were consistent in a validation subgroup that had completed at least four five-day cladribine cycles before year three and contributed more than three years of follow-up, a group referred to as the three-year follow-up subgroup. The subgroup analysis was assessed with Kaplan–Meier and log-rank methods.

Confirmed disability worsening and disability progression independent of relapses were uncommon. Approximately 10% of patients experienced these outcomes during the short-term period, while about 20% experienced them during longer-term follow-up. The relatively low proportions were observed even among patients aged 45 years or older. By contrast, loss of NEDA-3 resumed steadily during long-term follow-up and was largely unpredictable. Overall, the observed response appeared more favourable among older patients and among those without disease activity before baseline, although the study does not establish that cladribine caused these differences.

The findings point to strong short-term efficacy in the registry cohort, with substantially fewer annualised relapses after treatment began and comparatively rare confirmed disability-worsening events over both follow-up periods. However, the return of ongoing NEDA-3 loss means that the three-year results do not amount to uninterrupted control of all measured disease activity. Because this was an observational registry study, it cannot separate the effects of cladribine from other factors associated with relapse and disability outcomes. The small number of confirmed disability-worsening and relapse-independent progression events also limits conclusions about disability prevention. The researchers stated that optimal long-term management after cladribine treatment, and the drug’s role in preventing disability, require further research.

Subject of Research: Real-world short-term and long-term treatment outcomes with cladribine in relapsing–remitting multiple sclerosis

Article Title: Prediction of short-term and long-term responses to cladribine in relapsing–remitting multiple sclerosis: a Danish nationwide real-world study

Article References: Bramow, S., Pontieri, L., Heick, A., Thormann, A., Sejbæk, T., Rasmussen, P. V., Weglewski, A., Qadir, S. H., Christensen, J. R., Mærsk-Møller, C., Zachariassen, K., Schäfer, J., Stilund, M., Jensen, H. B., Kristensen, C. C. H., Kant, M., Sellebjerg, F., Sørensen, P. S., Magyari, M., … Danish Multiple Sclerosis Group (2026). Prediction of short-term and long-term responses to cladribine in relapsing–remitting multiple sclerosis: a Danish nationwide real-world study. Journal of Neurology, 273(11), 676. https://doi.org/10.1007/s00415-026-14152-x

Image Credits: AI Generated

DOI: 10.1007/s00415-026-14152-x

Keywords: cladribine, multiple sclerosis, relapsing–remitting MS, relapse rates, disability progression, disease activity, NEDA-3, Danish registry, real-world study, treatment response, Prediction, short-term

Finerenone is a selective, non-steroidal mineralocorticoid receptor antagonist. Unlike older steroidal antagonists such as spironolactone, it blocks the mineralocorticoid receptor with high selectivity, dampening the sodium and fluid retention as well as the profibrotic and proinflammatory signaling that overactivation of this receptor drives in kidney tissue. Randomized trials including FIDELIO-DKD and FIGARO-DKD established its renoprotective effects in patients with diabetic chronic kidney disease, and the recently completed FIND-CKD trial extended those benefits to non-diabetic chronic kidney disease, showing slowed decline in estimated glomerular filtration rate, the standard measure of kidney function. Real-world evidence in this broader population, however, has remained scarce, limited to small single-center studies with follow-up of twelve months or less.

To address that gap, a team at the First Affiliated Hospital of Xiamen University conducted a retrospective cohort study of adults with non-diabetic chronic kidney disease who initiated finerenone between January 2023 and December 2025. Because the drug’s use in non-diabetic patients was off-label at the time, each prescription was reviewed and approved by the institutional Drug and Therapeutics Committee based on clinical judgment. The researchers applied strict eligibility criteria: patients needed at least ninety days of regular finerenone use, a baseline estimated glomerular filtration rate of at least 20 mL/min/1.73 m2, urinary albumin-to-creatinine ratio of at least 30 mg/g, and stable background therapy for at least ninety days before the drug was added for persistent proteinuria. Patients with diabetes, baseline hyperkalemia, renal replacement therapy, or severe heart failure were excluded. After screening, 121 patients entered the final analysis.

The cohort was heterogeneous and relatively young, with a mean age of 45.2 years and just over half female. Mean baseline kidney function was 80.1 mL/min/1.73 m2, and median urinary protein excretion exceeded one gram per day. IgA nephropathy accounted for 42.1 percent of cases and membranous nephropathy for 28.1 percent. Most patients were already receiving guideline-recommended therapy, with 82.6 percent on renin-angiotensin system inhibitors and 45.5 percent on SGLT-2 inhibitors, while roughly a quarter received immunosuppressive agents such as tacrolimus, mycophenolate mofetil, or cyclophosphamide. Nearly all patients, 95 percent, started finerenone at a cautious 10 mg daily dose, with only 6.6 percent later uptitrated to 20 mg.

The results, published in Frontiers in Medicine, are striking. Using covariate-adjusted generalized estimating equation models with an autoregressive correlation structure and robust standard errors, the researchers found that the urinary albumin-to-creatinine ratio fell by an adjusted 48.6 percent at twelve months, a highly significant reduction. Total twenty-four-hour urinary protein declined by 34.5 percent at twelve months and remained significantly lower, at minus 34.9 percent, at twenty-four months. Albuminuria reductions appeared early, with a 22.1 percent drop already visible at one month and a 41.5 percent drop by three months, and remained statistically significant through month twenty-one.

Perhaps the most consequential finding concerned the trajectory of kidney function itself. By collecting all available serum creatinine measurements in the twelve months before treatment, the team could estimate each patient’s pre-treatment rate of decline. A segmented linear mixed-effects model with a knot at finerenone initiation revealed that the annualized eGFR slope improved from minus 6.51 mL/min/1.73 m2 per year before treatment to minus 1.44 afterward, a statistically significant improvement of 5.07 mL/min/1.73 m2 per year. In practical terms, kidneys that had been deteriorating at a pace likely to reach kidney failure within years were, on average, nearly stabilizing after the drug was added. Because eGFR slope is increasingly accepted as a surrogate endpoint for kidney failure risk, this attenuation carries substantial clinical weight.

The findings survived multiple sensitivity checks. Additional adjustment for kidney disease etiology and baseline severity barely changed the estimates, and replacing categorical baseline albuminuria with continuous log-transformed values yielded similar results. Exploratory subgroup analyses found nominally significant improvements across most strata, including patients with reduced baseline kidney function, heavy baseline proteinuria, and concomitant immunosuppression, although after false discovery rate correction only a time-by-RAS interaction for albuminuria remained significant, and the authors themselves caution that this should be viewed as exploratory rather than evidence of a definitively superior response in any subgroup.

Safety data were equally encouraging. No serious adverse events were documented during follow-up, which had a median duration of 434 days. Clinically defined hyperkalemia, serum potassium of 5.5 mmol/L or higher, occurred in only 4.96 percent of patients, or six of 121, and was managed with short-course potassium-lowering medication and dietary counseling without any treatment discontinuation. Neither hyperkalemia nor hypotension prompted anyone to stop the drug, and longitudinal estimates of serum potassium and blood pressure remained within clinically acceptable ranges throughout. The predominantly low starting dose and limited dose escalation likely contributed to this tolerability, although the authors note that conservative dosing may also have blunted the magnitude of the observed efficacy.

The study is not without limitations, and the authors are candid about them. The retrospective, single-center, single-arm design limits causal inference, and comparisons of treatment-period versus pre-treatment slopes can be influenced by regression to the mean, changes in background therapy, and variations in disease activity. The ninety-day treatment requirement may have introduced selection or survivor bias, excluding patients who discontinued the drug very early. Rolling enrollment meant that only twenty patients had available data at the twenty-four-month visit, making late estimates imprecise; the month-twenty-four albuminuria result, though numerically favorable, was no longer statistically significant. With 121 patients and a predominance of IgA nephropathy, generalizability also remains uncertain.

Even with those caveats, the convergence of three independent outcomes, reduced albuminuria, reduced total proteinuria, and a dramatically flattened eGFR slope, together with an infrequent and manageable hyperkalemia profile, offers the strongest real-world signal yet that finerenone belongs in the treatment conversation for non-diabetic chronic kidney disease. Larger prospective studies and more diverse populations will be needed to confirm causal benefit and define optimal dosing, but for the millions of patients whose kidneys continue to fail despite standard therapy, this study suggests that a drug developed for diabetic kidney disease may have a far broader role to play.

Subject of Research: Real-world effectiveness and safety of finerenone in patients with non-diabetic chronic kidney disease

Article Title: Longitudinal kidney outcomes and safety after finerenone initiation in patients with non-diabetic chronic kidney disease: a single-center retrospective cohort study

Article References: Sun, X., Pei, J., Chen, X., Wang, Z., Yao, L., Bai, P., Yan, Z., Li, Y., & Shao, L. (2026). Longitudinal kidney outcomes and safety after finerenone initiation in patients with non-diabetic chronic kidney disease: a single-center retrospective cohort study. Frontiers in Medicine, 13, Article 1959259. https://doi.org/10.3389/fmed.2026.1959259

Image Credits: AI Generated

DOI: 10.3389/fmed.2026.1959259

Keywords: finerenone, non-diabetic chronic kidney disease, mineralocorticoid receptor antagonist, albuminuria, eGFR slope, proteinuria, hyperkalemia, IgA nephropathy, membranous nephropathy, nephrology, real-world study, kidney disease progression

Zolbetuximab is a chimeric monoclonal antibody that targets claudin-18 isoform 2, or CLDN18.2, a protein found on gastric cancer cells but also on the normal mucosal lining of the stomach. Approved in combination with platinum- and fluoropyrimidine-based chemotherapy as a first-line treatment for patients with CLDN18.2-positive advanced gastric cancer, the drug has a distinctive safety profile dominated by nausea and vomiting. But as the new study makes clear, another adverse event—hypoalbuminemia and the peripheral edema it causes—has increasingly been recognized as a characteristic and potentially treatment-derailing complication of zolbetuximab-based therapy.

The discrepancy between trial data and clinical reality is striking. In an integrated analysis of the SPOTLIGHT and GLOW phase III trials, hypoalbuminemia was reported in 19.3 percent of patients for all grades combined, and in only 3.8 percent for grade 3 or higher events. In the Aichi cohort, by comparison, all 39 patients developed hypoalbuminemia of any grade, 24 patients—61.5 percent—reached grade 2, and seven patients, or 17.9 percent, reached grade 3. Serum albumin levels declined in all but one patient, with the median time to reach the lowest level during treatment being 34 days. Peripheral edema of any grade occurred in 46.1 percent of patients, and diuretics were administered to 41 percent.

The researchers, led by Taro Mizuno and Yukiya Narita, conducted their single-center retrospective study among patients with advanced gastric cancer who initiated zolbetuximab plus chemotherapy between July 2024 and August 2025 and received at least two cycles of treatment. Eligibility required immunohistochemical confirmation of HER2-negative, CLDN18.2-positive gastric or esophagogastric junction adenocarcinoma. The median age of the cohort was 61 years, most patients had a gastric primary tumor, and the peritoneum was the most common metastatic site, present in 84.6 percent of cases. Ascites—fluid accumulation in the abdomen—was present in 64.1 percent of patients, and 79.5 percent had diffuse-type adenocarcinoma, a histological subtype known for aggressive behavior.

To capture clinically meaningful albumin deterioration, the team defined severe hypoalbuminemia as a minimum serum albumin level below 2.0 grams per deciliter—the threshold for grade 3 events under the Common Terminology Criteria for Adverse Events—or a decrease of at least 1.0 grams per deciliter from baseline to the nadir during treatment. The second criterion was adopted because absolute grading alone can miss significant deterioration in patients who start with relatively high albumin levels. Using this definition, 20 patients, or 51.3 percent, developed severe hypoalbuminemia.

The search for risk factors produced two clinically important findings. Patients who experienced nausea, vomiting, or both persisting from the completion of the first treatment cycle to the initiation of the second had a significantly higher incidence of severe hypoalbuminemia than those without these symptoms—63.0 percent versus 25.0 percent. More striking still, no cases of severe hypoalbuminemia were observed among the five patients who had undergone prior total gastrectomy, compared with 58.8 percent among those whose stomach remained intact. Nausea, vomiting, or abdominal pain severe enough to require interruption of the first zolbetuximab infusion, and anorexia during the first cycle, showed trends toward association but did not reach statistical significance.

The gastrectomy finding carries particular mechanistic weight. Because zolbetuximab targets CLDN18.2, which is expressed not only on cancer cells but also on the normal gastric mucosa, the drug may damage the stomach lining itself, causing a protein-losing enteropathy—a syndrome in which plasma proteins leak through the gastrointestinal wall. This hypothesis is supported by an emerging case report describing zolbetuximab-induced protein-losing enteropathy characterized by diffuse gastric mucosal redness and edema, mucous cell detachment and fundic gland disruption on biopsy, and direct visualization of albumin leakage on technetium-99m albumin scintigraphy. The absence of severe hypoalbuminemia in patients without a stomach strongly suggests that CLDN18.2-expressing normal gastric mucosa is central to susceptibility to the drug’s albumin-depleting effects.

Perhaps the most actionable finding concerns reversibility. Recovery of serum albumin from the nadir back to baseline was observed in 18 patients, or 46.2 percent, with a median time to recovery of 64.5 days. No patients received albumin supplementation. Critically, patients who temporarily interrupted treatment for any reason after reaching their albumin nadir were significantly more likely to recover than those who continued treatment—66.7 percent versus 28.6 percent. Treatment was interrupted in 18 patients, with both zolbetuximab and chemotherapy withheld in 16 cases and zolbetuximab alone in two, for a median duration of 14 days. This pattern suggests that zolbetuximab-induced mucosal injury may be at least partially reversible when the drug is withheld, though the study could not determine whether such recovery translates into clinical benefit, nor whether edema improvement was attributable to interruption or to the diuretics most edema patients received.

Importantly, the presence of severe hypoalbuminemia did not appear to compromise treatment efficacy. Among the 10 patients with measurable lesions assessed by RECIST version 1.1 criteria, the objective response rate was 20.0 percent in patients without severe hypoalbuminemia and 60.0 percent in those with it, a difference that was not statistically significant given the small numbers. Among the 25 patients with baseline ascites, ascites response rates were 50.0 percent and 40.0 percent respectively. Survival analyses, with a median follow-up of 7.1 months, showed no significant differences in progression-free or overall survival according to severe hypoalbuminemia in either first-line or later-line settings, though the authors caution that these exploratory analyses were limited by wide confidence intervals, immature data, and potential time-dependent bias.

The study’s authors conclude that severe hypoalbuminemia is common during zolbetuximab plus chemotherapy in routine clinical practice, and that the absence of prior total gastrectomy and the presence of persistent post-infusion nausea or vomiting may help identify patients at increased risk of profound albumin decline. They also note that all patients in the cohort received acid-suppressive agents and gastric mucosal protectants under an institutional protocol, yet hypoalbuminemia still occurred universally—suggesting these measures alone are insufficient for prevention, and that careful monitoring with timely treatment modification may be a more appropriate strategy than excessive prophylactic medication. Limitations include the small sample size, the retrospective single-institution design, the possibility that disease progression contributed to albumin decline, and the lack of routine endoscopic assessment to directly correlate clinical findings with mucosal injury. Further validation, the team emphasizes, is needed to determine the optimal management of zolbetuximab-associated hypoalbuminemia without compromising the treatment’s anticancer efficacy.

Subject of Research: Zolbetuximab-associated hypoalbuminemia in CLDN18.2-positive advanced gastric cancer

Article Title: Retrospective Analysis of Zolbetuximab‐Associated Hypoalbuminemia in Claudin 18.2‐Positive Advanced Gastric Cancer

Article References: Mizuno, T., Narita, Y., Ando, T., Ishizuka, Y., Umegaki, S., Honda, K., Masuishi, T., Taniguchi, H., Kadowaki, S., Ando, M., Tajika, M., & Muro, K. (2026). Retrospective Analysis of Zolbetuximab‐Associated Hypoalbuminemia in Claudin 18.2‐Positive Advanced Gastric Cancer. Cancer Reports, 9(10), Article e70709. https://doi.org/10.1002/cnr2.70709

Image Credits: AI Generated

DOI: 10.1002/cnr2.70709

Keywords: zolbetuximab, gastric cancer, hypoalbuminemia, CLDN18.2, protein-losing enteropathy, peripheral edema, monoclonal antibody, advanced gastric cancer, treatment interruption, albumin recovery, chemotherapy, real-world study

The research team, led by Kaifei Yuan, Xianhong Hu, Qi Fang, Siyuan Li, Ping Lin, Baijing Ding, and Tongyuan Lin, analyzed 61 patients with Crohn’s disease treated between April 2022 and May 2025. Twenty-one patients were biologic-naïve, meaning ustekinumab was their first biologic therapy, while 40 were biologic-experienced, having previously failed treatment with agents such as infliximab, adalimumab, or vedolizumab. The investigators tracked clinical data, laboratory markers, disease activity scores, and endoscopic findings at baseline, week 8, and week 32, and separately assessed quality of life and psychological well-being at the start and end of the observation period.

Ustekinumab works by selectively binding the p40 subunit shared by interleukin-12 and interleukin-23, preventing these cytokines from engaging the IL-12Rβ1 receptor on immune cells. This disrupts downstream signaling that would otherwise activate natural killer cells and T cells, reducing the secretion of inflammatory mediators that drive chronic intestinal inflammation. The drug is recommended as a first-line biologic for induction and maintenance of remission in moderate to severe Crohn’s disease, yet questions have persisted about how prior biologic exposure shapes its real-world effectiveness.

At baseline, the two groups were statistically comparable in gender, age, disease duration, laboratory values, Crohn’s Disease Activity Index (CDAI) scores, and Simplified Endoscopic Score for Crohn’s Disease (SES-CD) scores. Most patients in the cohort were diagnosed between ages 17 and 40, and the majority had ileocolonic disease with non-stricturing, non-penetrating behavior. Dosing followed European Crohn’s and Colitis Organisation guidelines, with weight-based intravenous induction followed by 90 milligram subcutaneous injections every eight weeks.

Laboratory results revealed distinct response patterns between the groups. By week 8, erythrocyte sedimentation rate had fallen significantly in both cohorts, but the biologic-naïve group showed larger reductions in C-reactive protein and ESR than the biologic-experienced group. By week 32, the naïve group had achieved statistically significant improvements in CRP, platelet count, hemoglobin, and ESR, while the experienced group showed significant gains in albumin, platelets, red blood cells, hemoglobin, and ESR but no significant CRP improvement. The authors suggest that prior biologic exposure may alter ustekinumab trough concentrations, and that intestinal fibrosis or structural damage in previously treated patients may blunt the apparent decline in systemic inflammatory markers.

Clinical and endoscopic outcomes favored earlier intervention. At week 32, the biologic-naïve group achieved a mean CDAI reduction of 136.25 points compared with 102.28 points in the experienced group, and their mean SES-CD score fell by 5.48 points versus 3.80 points, both differences statistically significant. Despite these gaps, the overall clinical response rates were 61.9 percent in the naïve group and 52.5 percent in the experienced group, with remission rates of 42.9 percent and 40.0 percent respectively. The overlapping 95 percent confidence intervals indicate no statistically significant difference in short-term clinical efficacy between the two treatment strategies.

The study then reclassified all 61 patients into clinical responders and non-responders based on CDAI decline at week 32. Thirty-four patients achieved a clinical response, defined as a reduction of at least 100 points from baseline, while 27 did not. Quality of life, measured with the 32-item Inflammatory Bowel Disease Questionnaire, improved significantly in both groups, but the gain was markedly larger in responders, whose IBDQ scores rose by an average of 38.11 points compared with 20.56 points in non-responders. This finding underscores that effective control of intestinal inflammation remains the central driver of improved daily functioning in Crohn’s disease.

Psychological outcomes told a more nuanced story. Using the Hospital Anxiety and Depression Scale, the researchers found that anxiety scores fell significantly only in the clinical response group, dropping from a mean of 6.72 to 5.44, while depression scores showed no significant change in either group. The authors attribute the anxiety benefit to successful symptom control breaking the vicious cycle of gut-brain axis inflammation, in which persistent intestinal inflammation feeds back through neuroendocrine and autonomic pathways to sustain psychological distress. Depression, they note, is influenced by genetic and psychosocial factors beyond disease activity, and a 32-week follow-up may simply be too short to capture meaningful improvement.

The study has important limitations. As a single-center retrospective analysis with a modest sample size and unbalanced group allocation, it is vulnerable to selection bias and reduced statistical power. Only a subset of patients completed week-32 endoscopy, fecal calprotectin and therapeutic drug monitoring data were unavailable, and the investigators could not stratify outcomes by Montreal classification phenotype. Larger, multi-center prospective studies will be needed to confirm these findings and to identify which patients benefit most from early ustekinumab initiation.

Nevertheless, the results carry practical weight for clinicians managing a disease whose prevalence in China has climbed to an estimated 60 to 70 cases per 100,000 people and continues to rise. The data support a treatment philosophy already embedded in the 2023 Chinese national guidelines, which emphasize not only symptom control and normalization of inflammatory markers but also psychological health and overall quality of life. For patients with Crohn’s disease, the message is clear: ustekinumab can deliver meaningful benefit whether it is the first biologic tried or a rescue after failure of another agent, but the deepest and most durable improvements in inflammation, mucosal healing, and emotional well-being appear to belong to those who reach it earliest.

Subject of Research: Real-world comparative effectiveness of ustekinumab in biologic-naïve versus biologic-experienced Crohn's disease patients

Article Title: Retrospective analysis of ustekinumab in Crohn’s disease between biologic-naïve and biologic-experienced

Article References: Yuan, K., Hu, X., Fang, Q., Li, S., Lin, P., Ding, B., & Lin, T. (2026). Retrospective analysis of ustekinumab in Crohn’s disease between biologic-naïve and biologic-experienced. Frontiers in Gastroenterology, 5, Article 1926425. https://doi.org/10.3389/fgstr.2026.1926425

Image Credits: AI Generated

DOI: 10.3389/fgstr.2026.1926425

Keywords: ustekinumab, Crohn's disease, biologic-naïve, biologic-experienced, inflammatory bowel disease, CDAI, SES-CD, quality of life, anxiety, depression, IL-12/23, retrospective study

Bimekizumab represents a mechanistically distinct approach to psoriasis therapy. Where earlier biologics targeted single cytokines, bimekizumab is a monoclonal antibody that simultaneously neutralizes interleukin-17A and interleukin-17F, two closely related inflammatory signaling proteins that sit at the heart of the interleukin-23/T helper 17 axis driving psoriatic inflammation. Both cytokines are produced by activated T cells and other immune populations and act on keratinocytes, the dominant cell type of the epidermis, triggering the runaway proliferation, abnormal maturation, and recruitment of further immune cells that produce the thick, scaly plaques characteristic of the disease. Preclinical work has shown that interleukin-17F is co-expressed with interleukin-17A in psoriatic skin lesions, and that blocking both molecules suppresses downstream inflammatory gene expression more completely than blocking interleukin-17A alone. This dual inhibition is the theoretical basis for the exceptionally high clearance rates bimekizumab achieved in phase 3 randomized trials such as BE VIVID, BE READY, and BE SURE, where it outperformed both ustekinumab and secukinumab, a monoclonal antibody that targets only interleukin-17A.

Randomized controlled trials, however rigorous, enroll carefully selected patients under idealized conditions, and their populations often underrepresent the comorbidities, concomitant medications, and adherence patterns of everyday clinical practice. Real-world prospective studies fill that gap, and the new investigation, led by Manami Yoneyama and Teppei Hagino of Nippon Medical School Chiba Hokusoh Hospital together with colleagues at Nippon Medical School in Tokyo and the Fujimoto Dermatology Clinic in Funabashi, was designed to do exactly that. Between May 2022 and May 2025, the team prospectively followed 66 patients aged 15 years or older with moderate-to-severe plaque psoriasis who were treated with bimekizumab at a single center, assessing them repeatedly over two years with validated, site-specific scoring instruments rather than relying solely on whole-body measures.

The cohort was not selected for difficult-to-treat involvement, which makes the baseline data particularly informative. At the start of treatment, 58 of the 66 patients, or 87.9 percent, had scalp involvement; 42 patients, or 63.6 percent, had genital lesions; and 41 patients, or 62.1 percent, had nail disease. In other words, high-impact sites were the rule rather than the exception, mirroring the known epidemiology of psoriasis, in which genital involvement has been reported in a substantial proportion of patients and is frequently underdiagnosed because patients are reluctant to raise it with clinicians. Genital psoriasis in particular has been linked in prior research to marked impairment of quality of life and sexual functioning, while nail psoriasis can cause pitting, onycholysis, and functional disability of the hands, and scalp disease is a common source of visible flaking and social embarrassment.

The investigators scored each site with dedicated instruments. Genital lesions and fingernails were graded on physician’s global assessment scales, in which a score of zero indicates complete clearance, while the scalp was evaluated with the scalp-specific physician’s global assessment, or ss-PGA. The headline results at week 104 were striking: 77.8 percent of patients achieved complete clearance of genital psoriasis, 75 percent achieved a scalp-specific score of zero, and 44 percent achieved complete clearance of fingernail psoriasis. Nail disease is notoriously slow to respond to any therapy because the nail plate only reflects improvement as it grows out, so a 44 percent complete clearance rate at two years in an unselected real-world cohort is a meaningful result, even though nails remain the hardest of the three sites to clear.

Whole-body outcomes over the same period were robust and provide context for the site-specific figures. At week 104, 90.6 percent of patients had achieved a 75 percent reduction in their Psoriasis Area and Severity Index, or PASI 75; 71.9 percent achieved PASI 90; and 62.5 percent achieved PASI 100, meaning completely clear skin across the entire body surface. Even more telling, 93.8 percent of patients reached an absolute PASI score of two or lower, a threshold that many dermatologists now regard as the clinically relevant definition of minimal disease activity, since it accounts for how little disease a patient has rather than how much they improved from a high baseline. The parallel rise of the Dermatology Life Quality Index score of zero, achieved by 41.4 percent of patients at week 104, tracked closely with the clearance of genital and scalp lesions, reinforcing the argument that clearing these hidden sites is what translates biological improvement into a genuinely restored quality of life.

The study also captured a nuance that is often lost in headline efficacy figures. The achievement rates for genital, scalp, and nail clearance generally declined slightly during the second year, between week 52 and week 104, even though they remained high in absolute terms. The authors interpret this as a modest attenuation of effect during the later year of treatment rather than a loss of initial response, since the improvements established early were maintained through week 104. This pattern matters for clinicians and patients setting expectations: bimekizumab delivers rapid and deep clearance of difficult-to-treat sites in the first months of therapy, and the two-year data show that response is durable, but a small drift in the proportion of patients maintaining perfect clearance is observable over time in routine practice, where dosing intervals, concomitant illness, and other real-life factors differ from trial conditions.

The findings dovetail with the accumulating trial evidence for the drug. Two-year interim analyses from the open-label extension of the phase 3b BE RADIANT trial and the longer-term results from BE SURE and the extension of BE BRIGHT have already demonstrated that bimekizumab’s high skin clearance is sustained through two years in controlled settings, and pooled two-year analyses of phase 3 and 3b trials have specifically documented efficacy in high-impact areas including scalp, nail, and palmoplantar disease. What the new Japanese study adds is the first report of two-year outcomes for genital psoriasis with bimekizumab, a site for which such extended real-world data had not previously been published, together with confirmation that the drug performs well in a general clinic population rather than a curated trial cohort. Earlier work by the same group, including 24-week and 52-week real-world studies, had established the short-term signal; the present analysis extends that arc across a full two years.

For patients, the practical significance of these numbers is considerable. Genital psoriasis affects intimate relationships and self-image in ways that PASI scores barely capture, and the finding that more than three quarters of patients achieved completely clear genital skin at two years suggests that a substantial share of that hidden burden can be lifted and kept lifted. Scalp clearance at 75 percent and robust whole-body results at the same time point indicate that the dual interleukin-17A and interleukin-17F mechanism delivers consistent benefit across anatomically very different environments, from thin genital skin to thick scalp skin to the slow-growing nail unit. The study was conducted in accordance with the Declaration of Helsinki, approved by the institutional ethics committee, and carried out with informed consent from all participants, and the authors note that three of the investigators have received lecture fees from UCB, the drug’s manufacturer, while the remaining authors declare no conflicts of interest.

Caveats remain, as they do with any single-center observational study. There was no randomized comparator, the cohort of 66 patients is modest in size, and the slight second-year decline in clearance rates cannot be definitively attributed to any single mechanism without larger, controlled, multi-center data. Nevertheless, the study stands as the longest prospective real-world assessment of bimekizumab in genital, scalp, and nail psoriasis published to date, and it strengthens the case that dual blockade of interleukin-17A and interleukin-17F offers durable, site-specific clearance where patients need it most. As biologics with increasingly deep efficacy reshape the treatment goals of psoriasis from partial improvement to complete clearance, evidence that those goals remain achievable two years into routine clinical use, including in the regions patients find hardest to talk about, marks a genuine step forward in the care of this chronic immune-mediated disease.

Subject of Research: Long-term real-world effectiveness of bimekizumab for genital, scalp, and nail psoriasis

Article Title: Bimekizumab for the treatment of genital, scalp, and nail psoriasis: a 104-week real-world prospective study

Article References: Yoneyama, M., Hagino, T., Saeki, H., Fujimoto, E., & Kanda, N. (2026). Bimekizumab for the treatment of genital, scalp, and nail psoriasis: a 104-week real-world prospective study. Archives of Dermatological Research, 318(1), Article 417. https://doi.org/10.1007/s00403-026-04917-9

Image Credits: AI Generated

DOI: 10.1007/s00403-026-04917-9

Keywords: psoriasis, bimekizumab, interleukin-17A, interleukin-17F, genital psoriasis, scalp psoriasis, nail psoriasis, biologics, real-world study, PASI, dermatology, quality of life

The drugs in question are sodium–glucose cotransporter 2 inhibitors, known as SGLT2 inhibitors, and glucagon-like peptide-1 receptor agonists, or GLP-1 receptor agonists. Together they are described in the study as cardiorenal protective treatments because large outcome trials have shown that, beyond lowering blood glucose, they reduce the risk of cardiovascular events and slow the progression of kidney disease in people with type 2 diabetes. International and Chinese guidelines now recommend their use for patients at elevated cardiovascular or renal risk, making them a cornerstone of modern diabetes management rather than optional add-ons.

Yet a persistent question in clinical practice has been who actually receives these treatments, and whether prescribing reflects the specific risk profile of each patient. Generic averages can obscure the answer. A clinic population may show an overall utilization rate that looks reasonable while concealing large pockets of under-treatment among the very patients who stand to benefit most. This is precisely the kind of problem that phenotype clustering, a technique that groups patients by multidimensional similarity rather than by any single diagnostic label, is designed to address.

The research team, led by investigators at Peking University People’s Hospital and collaborating institutions across China, extracted baseline data from the iCaReMe China observational registry cohort, a multicenter effort to assess the management and quality of care for patients with type 2 diabetes, hypertension, heart failure, and chronic kidney disease. From this dataset of 9000 patients, they applied the Partitioning Around Medoids algorithm, a robust clustering method that builds groups around actual patient cases, called medoids, rather than around mathematical averages that can be distorted by outliers. The technique has gained traction in diabetes research in recent years, following influential work that identified novel subgroups of adult-onset diabetes in European, and subsequently Chinese and American, populations.

The resulting three clusters were clinically coherent and immediately recognizable to any practicing endocrinologist. Cluster 1 consisted of older patients carrying a high risk of atherosclerotic cardiovascular disease, the buildup of cholesterol-laden plaques in arteries that underlies heart attacks and strokes. Cluster 2 captured metabolically stable patients without cardiorenal risk, the comparatively healthy core of the diabetes population. Cluster 3 contained younger patients with obesity, high metabolic risk, and a short duration of diabetes, a profile increasingly common as the global burden of type 2 diabetes shifts toward earlier onset. The enrolled cohort had a median age of 55 years, was 60.8 percent male, and had a median diabetes duration of 5.37 years.

When the researchers compared prescribing patterns across the clusters, the differences were statistically significant. Overall utilization of cardiorenal protective treatments ranged from 44.1 percent in the metabolically stable Cluster 2, to 49.0 percent in the high cardiovascular risk Cluster 1, to 51.1 percent in the young, obese, high-risk Cluster 3, which had the highest rate of all three groups. Even so, the numbers mean that nearly half of patients in every cluster, including those with established risk factors, were not receiving a drug class that guidelines prioritize for exactly their situation.

The composition of treatment also diverged by phenotype. In the metabolically stable Cluster 2, prescribing was dominated by SGLT2 inhibitor monotherapy, which accounted for 73.1 percent of cardiorenal protective treatment in that group. Cluster 3, the younger patients with obesity and high metabolic risk, showed a marked preference for GLP-1 receptor agonist-based regimens, which made up 43.6 percent of use in that cluster. Cluster 1, the older patients at high atherosclerotic risk, fell in between, with 31.5 percent of their cardiorenal protective treatment involving GLP-1 receptor agonists. These divergent patterns plausibly reflect the differing secondary benefits of the two drug classes: GLP-1 receptor agonists are associated with substantial weight reduction, which is particularly relevant for the obese younger phenotype, while SGLT2 inhibitors have established benefits for heart failure and kidney outcomes, relevant to older patients with cardiovascular burden.

The technical significance of the study lies in its multilevel correlation framework, which links patient-level phenotypes to treatment-level decisions within a standardized analytical structure. Rather than treating the diabetes population as a monolith, the framework allows clinicians and health system planners to ask how a specific, well-defined subgroup is being treated and whether that treatment matches the evidence. Partitioning Around Medoids is particularly suited to this task because it works with mixed clinical variables and produces interpretable representative cases for each cluster, making the groups easier to communicate than abstract statistical dimensions.

The findings arrive at a moment of mounting global urgency. The Global Burden of Disease Study 2021 estimated more than 800 million people living with diabetes worldwide, with prevalence projected to continue rising through 2050, and cardiovascular disease remains the leading cause of death in people with type 2 diabetes. Identifying the patients most likely to benefit from cardiorenal protective therapy, and the subgroups in which those drugs are being underused, is therefore a matter of population-scale consequence. The observation that the metabolically stable cluster still received cardiorenal protective agents at a rate of 44 percent, while remaining under-treated overall, illustrates both the diffusion of these therapies into routine practice and the gap that persists.

For clinical practice, the study’s message is that phenotype-aware prescribing could sharpen the use of SGLT2 inhibitors and GLP-1 receptor agonists, ensuring that older patients with atherosclerotic risk and younger patients with obesity-driven metabolic risk each receive the drug class best matched to their profile. The authors note that three clinically distinct phenotypes were reliably identified and that prescribing patterns already differ meaningfully across them, providing a foundation for standardized application of cardiorenal protective treatments. As registries like iCaReMe China continue to accumulate longitudinal data, cluster-based frameworks of this kind may become a routine instrument for auditing and improving the quality of diabetes care, turning the promise of precision medicine into an operational reality for hundreds of millions of patients.

Subject of Research: Phenotype cluster analysis of cardiorenal protective glucose-lowering treatment patterns in type 2 diabetes

Article Title: Cardiorenal Protective Glucose-Lowering Treatment Patterns in Type 2 Diabetes Mellitus Based on a Real-World Study: A Clinical Phenotype Cluster Analysis

Article References: Yang, W., Bai, S., Cai, X., Liu, M., Ji, Q., Li, Y., Feng, B., Tong, N., Wu, H., Yan, J., Zhao, W., & Ji, L. (2026). Cardiorenal Protective Glucose-Lowering Treatment Patterns in Type 2 Diabetes Mellitus Based on a Real-World Study: A Clinical Phenotype Cluster Analysis. Advances in Therapy. https://doi.org/10.1007/s12325-026-03826-7

Image Credits: AI Generated

DOI: 10.1007/s12325-026-03826-7

Keywords: type 2 diabetes, SGLT2 inhibitors, GLP-1 receptor agonists, cardiorenal protection, cluster analysis, clinical phenotypes, real-world study, precision medicine, obesity, cardiovascular risk, diabetes guidelines, registry study

Rapid intravenous opioid titration is a deceptively simple concept. Rather than waiting hours for oral medications to take effect, clinicians administer small intravenous boluses of an opioid — typically morphine — every two minutes, reassessing the patient’s symptoms and side effects after each dose. The process continues until adequate relief is achieved, a clinically relevant adverse event appears, or further dose escalation yields no benefit. International guidelines from ESMO, ASCO, and the European Association for Palliative Care recommend opioids for severe cancer pain and dyspnea, but the evidence base for the rapid titration variant has remained thin, drawn largely from small single-center cohorts. The CHUV team set out to describe how the technique actually works in routine practice.

The retrospective observational study included 38 consecutive adult inpatients who underwent rapid intravenous opioid titration for an acute severe pain or dyspnea crisis between April 2024 and February 2026. All patients had cancer, with 68 percent presenting with stage IV disease, and the most frequent primary tumors were upper gastrointestinal, urogenital, and lung cancers. The median age was 63 years, and the median Charlson Comorbidity Index was 8, reflecting a heavily burdened patient population. Crucially, 87 percent of patients were already receiving baseline opioid therapy, predominantly oral morphine at a median dose of 80 milligrams per day in oral morphine equivalents — meaning most titrations were not starting from scratch but recalibrating existing therapy in the face of a sudden crisis.

The technical details of the titration procedure reveal how individualized the approach is. For patients already on opioids, clinicians generally used the same molecule intravenously, deriving the initial bolus from the patient’s baseline regimen. Opioid-naive patients typically started with low-dose intravenous morphine. The median initial dose was just 5 milligrams in intravenous morphine equivalents, and patients required a median of only 3 boluses to reach symptom control. The median cumulative opioid exposure was 12 milligrams IME, and the median titration duration was a strikingly short 8 minutes. Every bolus was administered under close bedside supervision by palliative care physicians and nursing staff, with symptom intensity and tolerability reassessed continuously throughout.

The results were dramatic. Among the 34 patients treated primarily for pain, median pain intensity on the Numerical Rating Scale fell from 8 to 2, a median reduction of 5 points, with a p-value below 0.001. Ninety percent of all patients met the predefined responder criteria — a reduction of at least 2 points on the pain scale or an improvement of at least one category on the Verbal Descriptor Scale used for breathlessness. All four patients treated for dyspnea improved, shifting from predominantly severe breathlessness at baseline to predominantly mild dyspnea afterward. Titration was successfully completed in 82 percent of patients, with the remaining cases split between four discontinuations due to adverse events and three due to insufficient symptom relief.

Tolerability data were equally encouraging, though nuanced. Some form of adverse event occurred in 39 percent of patients, but the vast majority were mild, grade 1 events. The most common were somnolence, affecting 26 percent of patients, and dizziness, affecting 11 percent. Only one patient experienced a grade 3 event — severe somnolence that resolved with observation alone. Clinically relevant adverse events, defined as grade 2 or higher or any event forcing premature discontinuation, occurred in just 4 patients, or 11 percent of the cohort. Notably, despite the high prevalence of pre-existing opioid exposure and the speed of dose escalation, the cumulative opioid doses remained modest, suggesting that the technique achieves control with less drug than clinicians might fear.

Perhaps the most patient-centered finding came at the 24-hour mark: 76 percent of patients reported complete satisfaction with their symptom management when directly questioned during routine clinical assessment. The statistical analysis revealed a clear pattern behind those numbers. Patients who reported complete satisfaction had experienced greater symptom improvement, with a median NRS change of 5 points compared with 2 points among those only partially satisfied or unsatisfied, a difference that reached statistical significance. Conversely, patients who suffered clinically relevant adverse events reported significantly lower satisfaction. The message, the authors suggest, is that efficacy and tolerability must be balanced in real time — both shape how patients remember their care.

The findings align with a small but consistent body of prior work. Earlier studies using intravenous morphine or oxycodone in advanced cancer patients have similarly reported meaningful pain relief within minutes and low rates of significant toxicity. What distinguishes the CHUV study is its grounding in unselected daily practice rather than a protocolized research setting. Because the data reflect what actually happened when specialist palliative physicians reached for this tool at the bedside, they provide a realistic picture of feasibility — how many boluses are truly needed, how long titration takes, and how often things go wrong when the technique is deployed under ordinary clinical pressures.

The authors are careful to enumerate the study’s limitations, and they matter. The retrospective design introduces potential selection and information bias. The sample was small, particularly for dyspnea, where only four patients were treated, limiting statistical power. The single tertiary center setting may restrict generalizability, and the absence of a standardized titration protocol — while faithful to real-world practice — introduces variability. As an observational study, placebo effects cannot be excluded. Adverse events were systematically assessed only during titration and for 20 minutes afterward, so delayed opioid toxicity, including delirium occurring later, may have gone undetected. Satisfaction measured at 24 hours also cannot be attributed exclusively to the titration, since subsequent changes to baseline opioid regimens were not systematically collected. And because every patient had cancer, extrapolation to non-malignant serious illness should be cautious.

Even with those caveats, the study delivers a compelling real-world signal: rapid intravenous opioid titration, performed under close specialist supervision, was associated with substantial and fast symptom improvement, high patient-reported satisfaction, and a low rate of clinically relevant adverse events during the monitored window. The authors argue that further prospective studies are warranted to define optimal use and longer-term safety, while acknowledging that placebo-controlled trials in patients experiencing severe pain or breathlessness raise serious ethical concerns and may prove difficult to conduct. For now, the message for palliative care teams is that an eight-minute, three-bolus intervention — delivered with vigilance — may be one of the most efficient ways to pull a dying patient back from the edge of an unbearable crisis.

Subject of Research: Rapid intravenous opioid titration for acute pain and dyspnea crises in palliative care

Article Title: Rapid intravenous opioid titration for acute symptom crises in palliative care: a real-world retrospective study

Article References: Nasrinfar, K., Simonet, V., Trippini, A., Bosia, T., Bruera, E., & Gamondi, C. (2026). Rapid intravenous opioid titration for acute symptom crises in palliative care: a real-world retrospective study. Supportive Care in Cancer, 34(10), Article 1010. https://doi.org/10.1007/s00520-026-11245-1

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11245-1

Keywords: palliative care, opioids, intravenous titration, cancer pain, dyspnea, morphine, symptom crisis, patient satisfaction, adverse events, palliative medicine, real-world study, Lausanne University Hospital

The study, led by researchers at Shandong Cancer Hospital and Institute together with collaborators at Sichuan Cancer Hospital and Shandong Provincial Hospital, analyzed 465 patients with EGFR-mutant non-small-cell lung cancer who had brain metastases at their initial diagnosis and had never previously received brain-directed treatment. All of the patients began treatment with a first-line, third-generation epidermal growth factor receptor tyrosine kinase inhibitor, the class of drugs that includes osimertinib and has become the standard of care for this molecular subtype of lung cancer. The researchers then divided the cohort into three groups according to how radiotherapy fit into the treatment sequence: 92 patients received the targeted drug alone, 229 received brain radiotherapy concurrently with the drug, and 144 received the drug first with radiotherapy held in reserve as a salvage treatment.

Because this was a retrospective, real-world study rather than a randomized trial, the patients in the three groups differed in ways that could independently affect their outcomes, such as age, performance status, the burden of brain disease, and the extent of cancer elsewhere in the body. To address this, the investigators used a statistical technique called inverse probability of treatment weighting, which mathematically reweights the cohorts so that baseline characteristics are balanced between groups, mimicking some of the conditions of a randomized experiment. They also performed propensity score matching between the two radiotherapy groups as a second layer of adjustment. The primary endpoint was overall survival, with intracranial progression-free survival and total progression-free survival as secondary endpoints, and safety was assessed using the National Cancer Institute’s Common Terminology Criteria for Adverse Events, version 5.0.

The headline result concerns the value of adding radiation at all. In the weighted analysis, both radiotherapy strategies were associated with markedly lower mortality compared with the targeted drug alone. Patients who received concurrent brain radiotherapy with their third-generation EGFR inhibitor had a hazard ratio for death of 0.36, and those who received salvage radiotherapy had a hazard ratio of 0.29, meaning that in both cases the risk of dying at any given time was roughly a third of that seen in patients treated with the drug alone. In a disease where brain metastases have historically been a dominant cause of illness and death, the message is that modern targeted therapy and radiation are not redundant weapons but complementary ones.

The more nuanced and clinically consequential finding emerged when the researchers compared the two radiotherapy timing strategies directly. After propensity score matching, overall survival was statistically indistinguishable between the concurrent and salvage approaches, at 31.2 months versus 35.7 months, a difference that did not reach significance. But intracranial progression-free survival, the length of time the cancer in the brain remained under control, was significantly longer with the concurrent strategy: 22.4 months compared with 14.5 months, with a hazard ratio of 0.51. In other words, waiting for brain progression before irradiating cost patients roughly eight months of intracranial control, even though it did not ultimately shorten how long they lived.

This distinction matters because intracranial progression is not a benign event. When brain metastases grow, patients can develop headaches, seizures, weakness, and cognitive decline, and salvage options become progressively more limited. Delaying radiation also means that a patient spends more months with active disease inside the blood-brain barrier, the protective interface that many drugs penetrate imperfectly. The concurrent approach, by attacking the brain disease with both a drug and radiation from the outset, appears to close that window of vulnerability. The finding that overall survival was preserved despite earlier radiation also speaks to the tolerability of the combination in appropriately selected patients.

Safety data provided further reassurance. The incidence of grade 3 or higher treatment-related adverse events did not differ significantly according to whether the EGFR inhibitor was continued without interruption or temporarily paused during the course of brain radiotherapy. This is an important practical point, because clinicians have long debated whether to hold targeted drugs during cranial irradiation out of concern for overlapping toxicities, particularly radiation-induced brain injury and skin or esophageal effects. The real-world data suggest that neither approach to drug management during radiotherapy carried a clearly higher risk of severe toxicity, giving treating teams flexibility in how they sequence care around radiation appointments.

Perhaps the most clinically actionable result was the identification of which patients benefit most from the concurrent strategy. The researchers found that extracranial metastatic status was the only factor showing a significant interaction with the overall survival benefit, with a P value for interaction of 0.031. In plain terms, whether a patient’s cancer had spread beyond the brain to other organs changed how much the timing of radiotherapy mattered. Patients whose disease was confined to the brain, or whose extracranial disease was limited, emerged as the group for whom concurrent brain radiotherapy is most clearly supported as a reasonable strategy. For patients with widespread disease outside the brain, systemic control becomes the dominant concern, and the calculus shifts.

The study arrives at a moment of genuine uncertainty in the field. Randomized trials examining the addition of radiotherapy to third-generation EGFR inhibitors have produced mixed and sometimes conflicting results, and professional guidelines, including the American Radium Society Appropriate Use Criteria, have left room for individualized decision-making. Real-world evidence of this kind cannot replace randomized trials, and the authors are careful to frame their findings as supporting concurrent radiotherapy for selected patients rather than as a universal prescription. Retrospective designs remain vulnerable to selection biases that even sophisticated weighting cannot fully eliminate, and the patients who received concurrent treatment may have differed from those who waited in ways that no statistical model can capture completely.

Nevertheless, the scale and multicenter design of the analysis give the findings unusual weight for real-world data. Drawing patients from three Chinese cancer centers, applying rigorous propensity methods, and reporting both efficacy and safety endpoints, the study provides the kind of granular, practice-relevant evidence that randomized trials often cannot, simply because trials enroll selected populations under idealized conditions. For the growing population of patients diagnosed with EGFR-mutant lung cancer and brain metastases at baseline, the study suggests a clearer path forward: targeted therapy remains the backbone, but radiation to the brain should not be reflexively deferred, and for patients without extensive disease elsewhere in the body, delivering it alongside the first targeted drug may buy the brain precious additional months of control. As third-generation EGFR inhibitors continue to extend lives, the question is shifting from whether these drugs work to how best to combine them with the other tools in the oncology arsenal, and this study moves that answer meaningfully forward.

Subject of Research: Timing of brain radiotherapy combined with third-generation EGFR-TKIs in EGFR-mutant NSCLC with treatment-naïve brain metastases

Article Title: Brain radiotherapy synergizes with first-line, third-generation EGFR-TKIs in patients with EGFR-mutant NSCLC and treatment-naïve brain metastases: a multicenter real-world study

Article References: Deng, G., Song, X., Liang, L., Fan, J., Shen, H., & Li, Z. (2026). Brain radiotherapy synergizes with first-line, third-generation EGFR-TKIs in patients with EGFR-mutant NSCLC and treatment-naïve brain metastases: a multicenter real-world study. BMC Medicine. https://doi.org/10.1186/s12916-026-05241-9

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05241-9

Keywords: EGFR-mutant NSCLC, brain metastases, brain radiotherapy, EGFR-TKIs, concurrent therapy, salvage radiotherapy, intracranial progression-free survival, overall survival, real-world study, inverse probability of treatment weighting, targeted therapy, radiation oncology

The study, led by Tomás José González-López of Hospital Universitario de Burgos and colleagues across 22 Spanish centers, analyzed 72 adults with ITP drawn from a broader national cohort of 174 patients who had received the drug. The median age of participants was 67 years, and 55.6 percent were women, a demographic profile that reflects the typical real-world ITP population far better than the carefully selected patients enrolled in pharmaceutical registration trials. Half of the patients carried at least one comorbidity on the Charlson Comorbidity Index, and roughly a quarter had experienced bleeding in the month before starting fostamatinib, underscoring the clinical urgency that often drives treatment decisions in this disease.

ITP is an acquired immune-mediated disorder in which platelet counts fall because of a double hit: antibodies and cytotoxic T lymphocytes accelerate platelet destruction in the spleen and elsewhere, while defective megakaryocyte maturation impairs the production of replacement platelets in the bone marrow. The clinical course is highly variable. Some patients remain asymptomatic despite platelet counts well below 100 × 10⁹ per liter, while others suffer significant mucocutaneous bleeding or develop chronic, relapsing disease that demands years of therapy. Beyond the bleeding risk itself, ITP carries a substantial burden on quality of life and healthcare resources, particularly for patients who cycle through multiple treatment lines without achieving durable control.

Standard first-line therapy remains corticosteroids, sometimes supplemented by intravenous immunoglobulin when rapid platelet increases are needed. Although initial steroid responses are high, relapse after dose tapering is common, and many patients become corticosteroid-dependent with all the metabolic and infectious complications that entails. Second-line options include thrombopoietin receptor agonists such as eltrombopag and romiplostim, the anti-CD20 antibody rituximab, and splenectomy. Each has drawbacks: TPO receptor agonists require continuous administration and raise concerns about thromboembolic risk in some patients, while rituximab and splenectomy can produce durable remissions but carry delayed onset, variable long-term efficacy, and procedure- or immunosuppression-related hazards. Guidelines therefore emphasize individualized sequencing, and the search for well-tolerated earlier options has intensified.

Fostamatinib attacks the disease from a different angle. As an oral inhibitor of spleen tyrosine kinase, or SYK, it interferes with Fcγ receptor signaling in macrophages, the scavenger cells that phagocytose antibody-coated platelets. By blocking this pathway, the drug reduces antibody-dependent platelet destruction rather than simply stimulating platelet production. Its efficacy and safety were established in the pivotal phase 3 FIT trials in patients with persistent and chronic ITP who had already received multiple prior therapies, leading to regulatory approval for chronic ITP in adults refractory to other treatments. But those trials, by design, tested the drug late in the disease course, leaving a gap in evidence about how it performs when introduced earlier.

The new Spanish study was designed to fill that gap. Patients received fostamatinib at the European Medicines Agency-approved starting dose of 100 milligrams twice daily, with escalation to 150 milligrams twice daily after four weeks if platelet responses were inadequate and tolerability permitted. Fifty-six point nine percent of patients ultimately required the higher dose, typically after a median of 24 days. Forty patients, or 55.5 percent, took fostamatinib as monotherapy throughout their treatment, while the remainder used it alongside tapering corticosteroids, immunoglobulin, or other agents. The median time from ITP diagnosis to fostamatinib initiation was 17 months, and the baseline platelet count stood at just 28 × 10⁹ per liter.

The effectiveness results were striking. Overall, 83.3 percent of patients achieved a response, defined as a platelet count of at least 30 × 10⁹ per liter with at least a twofold increase from baseline, resolution of bleeding, and no rescue therapy within the preceding eight weeks. Complete response, meaning a platelet count of at least 100 × 10⁹ per liter, was reached by 65.3 percent. When fostamatinib was used as second-line therapy, 76.0 percent responded, with 56.0 percent achieving complete response; in the third-line setting, the figures rose to 87.2 percent and 70.2 percent respectively. The median time to platelet response was a brisk 10.5 days, and patients reached their peak platelet counts, a median of 140 × 10⁹ per liter, after a median of 62 days. Across the 42-month observation window, patients spent a cumulative 76.8 percent of their time in response.

Exploratory subgroup analyses hinted at interesting patterns, though the investigators caution that these were hypothesis-generating and based on small numbers. Response rates were higher among women than men, 92.5 versus 71.9 percent, and higher in chronic than in non-chronic ITP by the same margin. Patients previously treated with eltrombopag responded more often than those without such exposure, 96.3 versus 75.6 percent, while prior romiplostim exposure was associated with a lower rate. Notably, second-line use was associated with faster platelet recovery, a median of 32 days to peak count compared with 77 days for third-line use, suggesting that earlier introduction may speed benefit even when overall efficacy is similar. Twenty-seven point eight percent of patients discontinued the drug for insufficient effectiveness, and only four patients, 5.5 percent, managed to stop fostamatinib successfully after responding, indicating that the drug is best regarded as long-term maintenance therapy rather than a finite course.

Safety data were reassuring. Adverse events occurred in 44.4 percent of patients and were predominantly mild to moderate, with diarrhea, hypertension, and headache the most common complaints, generally manageable with symptomatic treatment. Only 15.3 percent of patients stopped the drug because of toxicity, and severe grade 3 to 4 events were infrequent. Three thromboembolic events occurred, two deep vein thromboses and one pulmonary embolism, but all three patients had established thrombotic risk factors unrelated to the drug, including advanced age, obesity, and immobilization. Given growing recognition that ITP itself carries an elevated thrombotic risk, the low incidence observed here, 4.2 percent, may represent a meaningful advantage for patients with cardiovascular comorbidities, a group well represented in this elderly cohort.

The findings align with a growing body of international real-world evidence, including the Spanish FOSTASUR study, the Italian GIMEMA ITP 1122 experience, and a post hoc analysis of the FIT trials that reported response rates of 94 percent and 86 percent for second- and third-line use respectively. The authors acknowledge the limitations inherent to an observational design without a control group, but the consistency across independent cohorts strengthens the case. Their conclusion is direct: fostamatinib should be considered earlier in the ITP treatment algorithm rather than reserved as a last resort, with prospective studies now needed to define the optimal timing and sequencing of a drug that, for many patients, may offer rapid, durable platelet recovery with an acceptable safety profile.

Subject of Research: Real-world effectiveness and safety of early-line fostamatinib therapy in adult immune thrombocytopenia

Article Title: Early Use of Fostamatinib in Immune Thrombocytopenia

Article References: González-López, T. J., Bermejo-Vega, N., Cardesa-Cabrera, R., Acedo, N., Luis-Navarro, J., Lakhwani, S., Bernat, S., Haces-Tirado, G. E., Galán, P., Lozano, M. L., Martínez-Carballeira, D., Hernández-Martin, R., Jimenez-Bárcenas, R., Navas-Elorza, B., Marcellini, S., Torres-Tienza, A., Perona-Blázquez, A., Benet, C., Fernandez-Jimenez, D., … García-Donás Gabaldón, G. (2026). Early Use of Fostamatinib in Immune Thrombocytopenia. Advances in Therapy. https://doi.org/10.1007/s12325-026-03769-z

Image Credits: AI Generated

DOI: 10.1007/s12325-026-03769-z

Keywords: immune thrombocytopenia, fostamatinib, SYK inhibitor, second-line therapy, third-line therapy, platelet response, real-world study, hematology, autoimmune disease, drug safety, thrombosis risk, Spain

Diffuse large B-cell lymphoma, or DLBCL, is the most frequent subtype of non-Hodgkin lymphoma, accounting for approximately 30 to 40 percent of all cases. For two decades, the frontline standard of care was R-CHOP, a five-drug immunochemotherapy combining the monoclonal antibody rituximab with three chemotherapeutic agents and a corticosteroid. Despite countless attempts to improve upon it with novel agents, R-CHOP remained essentially unchallenged until the POLARIX trial demonstrated that swapping vincristine for polatuzumab vedotin—a targeted antibody-drug conjugate directed against CD79b, a signaling component of the B-cell receptor—produced significantly superior outcomes. That result transformed Pola-R-CHP into the new global standard for previously untreated DLBCL, and the regimen was approved in China in April 2023 for adult patients.

Yet the POLARIX trial enrolled only patients with international prognostic index scores of 2 through 5, meaning patients considered to have intermediate or high-risk disease. The IPI is a well-established scoring system that predicts prognosis in DLBCL using five factors: age, tumor stage, number of extranodal sites involved, performance status, and serum lactate dehydrogenase levels. Patients scoring 0 or 1 are conventionally labeled low-risk and represent approximately 30 percent of newly diagnosed cases. Because they were excluded from the pivotal trial, this substantial population became a critical evidence gap. The problem is compounded by the fact that low IPI scores do not guarantee biological simplicity. Many of these patients carry molecular and pathological features known to undermine standard therapy, including bulky tumors, double-expressor lymphoma, and abnormalities of the TP53 gene, the so-called guardian of the genome.

The new study, led by Yuhong Ren and Peng Liu of Zhongshan Hospital, Fudan University, together with colleagues across China, set out to fill that gap using real-world data. Between June 2023 and July 2025, the researchers enrolled 118 consecutive previously untreated DLBCL patients with IPI scores of 0 or 1 who received at least one cycle of Pola-R-CHP. The median age was 53.5 years, with patients ranging from 17 to 87 years old. Despite their formally low-risk classification, the cohort was biologically heterogeneous and carried a surprising burden of adverse features: 51.7 percent had the non-germinal center B-cell-like subtype, 24.6 percent had double-expressor lymphoma, 9.3 percent had double-hit or triple-hit lymphoma, 25.4 percent showed high P53 expression, 12.7 percent had bulky disease, and 62.7 percent had extranodal involvement.

The treatment protocol followed a well-defined structure. Each 21-day cycle comprised polatuzumab vedotin at 1.8 milligrams per kilogram of body weight, rituximab at 375 milligrams per square meter, cyclophosphamide at 750 milligrams per square meter, doxorubicin at 50 milligrams per square meter or epirubicin at 70 milligrams per square meter, and prednisone at 100 milligrams orally for five consecutive days. Patients received a median of six cycles. Efficacy was assessed using whole-body fluorodeoxyglucose PET/CT or contrast-enhanced CT imaging after three to four cycles and again at the end of treatment, with responses graded according to the 2014 Lugano classification, the international standard for lymphoma response assessment.

The results were remarkable. Among the 68 patients who had completed end-of-treatment evaluation at the data cut-off of August 2025, 63 achieved a complete response, yielding a complete response rate of 92.6 percent. The overall response rate reached 98.5 percent at end of treatment and 98.9 percent at interim assessment, with 78.2 percent of interim-evaluated patients already in complete remission after just three to four cycles. Only two patients experienced disease progression during follow-up, both of whom had central nervous system involvement, and no deaths occurred at a median follow-up of 7.1 months. Importantly, the 50 patients without end-of-treatment assessment had not progressed, died, or been lost to follow-up; they were simply still undergoing treatment or awaiting imaging, meaning the missing data reflected short follow-up rather than treatment failure.

Perhaps most striking was the consistency of responses across molecular subgroups. Exploratory analyses showed broadly similar response rates at both interim and end-of-treatment time points among elderly patients, those with the non-germinal center subtype, extranodal disease, double-expressor lymphoma, and double-hit or triple-hit lymphoma. The one exception was the high P53 expression subgroup, where the complete response rate was numerically lower at 78.6 percent compared with 96.9 percent in patients with low or absent P53 expression. This finding aligns with the well-documented biology of TP53 alterations, which are associated with genomic instability and chemoresistance in lymphoma. However, the researchers caution that the small number of evaluable patients in this subgroup prevents definitive conclusions, and they suggest that the bystander effect of antibody-drug conjugates—the ability of the drug payload to diffuse into neighboring tumor cells that may not express the target antigen—could theoretically help overcome the clonal heterogeneity that drives resistance.

Safety data from all 118 patients showed a tolerable profile without unexpected toxicity compared with the POLARIX trial. Any grade 3 or 4 adverse event occurred in 24.6 percent of patients. The most common adverse events overall were anemia in 68.6 percent, leukopenia in 47.5 percent, and decreased neutrophil count in 39.8 percent, the vast majority of which were mild to moderate. The most frequent severe toxicity was neutropenia, affecting 21.2 percent of patients at grade 3 or 4—a manageable side effect routinely addressed with dose adjustments and growth factor support in clinical practice. No new safety signals emerged, reinforcing the regimen’s established risk-benefit profile in a broader and more diverse population than the original trial captured.

The study’s authors place their findings in context by comparing them with other real-world cohorts and historical R-CHOP data. Published complete response rates for frontline Pola-R-CHP and R-CHOP in low-risk patients range from 80.6 to 96.5 percent, and the current results sit comfortably at the upper end of that spectrum. Notably, the Chinese cohort carried a heavier burden of adverse features than a comparable R-CHOP cohort from a Chinese phase 3 trial, with higher rates of impaired performance status, advanced stage disease, and double-expressor lymphoma, yet still achieved outstanding responses. The researchers acknowledge the inherent limitations of a retrospective, single-arm design conducted exclusively in China, including potential selection bias and immature survival data, and they emphasize that a conservative sensitivity analysis counting all unevaluated patients as non-responders still yielded a complete response rate of 85.1 percent.

The implications reach beyond the numbers. Roughly a third of DLBCL patients worldwide fall into the IPI 0-1 category, yet they remain underrepresented in clinical trials and continue to experience late relapses even in limited-stage disease, a pattern that contrasts with the survival plateau seen in advanced-stage patients. This study provides the first multicenter real-world evidence that Pola-R-CHP is both effective and tolerable in this population, even when adverse biological features are present. The authors call for prospective randomized trials to precisely define the magnitude of benefit, and for molecular subtyping strategies to better identify which low-risk patients harbor hidden resistance mechanisms. For now, the message for clinicians is clear: the antibody-drug conjugate revolution in lymphoma treatment appears to extend to nearly every patient who walks through the door, not just those who fit the narrow criteria of a registration trial.

Subject of Research: Frontline Pola-R-CHP treatment of low-risk diffuse large B-cell lymphoma

Article Title: Pola-R-CHP in previously untreated DLBCL with international prognostic index score 0–1: a multicenter real-world retrospective study in China

Article References: Ren, Y., Liu, J., Lin, Z., Shou, L., Zeng, H., Wu, D., Zeng, Z., Zhou, F., Bao, L., Jing, H., Jiang, S., Liu, H., Shen, J., Yu, W., Zhou, H., Xu, J., Zhang, Y., Wang, T., Huang, H., … Liu, P. (2026). Pola-R-CHP in previously untreated DLBCL with international prognostic index score 0–1: a multicenter real-world retrospective study in China. Clinical Cancer Bulletin, 5(1), Article 21. https://doi.org/10.1007/s44272-026-00073-3

Image Credits: AI Generated

DOI: 10.1007/s44272-026-00073-3

Keywords: diffuse large B-cell lymphoma, Pola-R-CHP, polatuzumab vedotin, antibody-drug conjugate, international prognostic index, real-world study, R-CHOP, double-expressor lymphoma, TP53, complete response, non-Hodgkin lymphoma, immunochemotherapy