The concept at the heart of the study is called drug survival, a term that can mislead people unfamiliar with pharmacoepidemiology. Drug survival does not refer to whether the patient survives; it refers to how long a patient remains on a given medication before stopping it for any reason. That reason might be lack of efficacy, an adverse event, intolerance, loss of effectiveness over time, or a practical barrier such as cost or insurance coverage. Because drug survival aggregates all of these causes into a single longitudinal measure, it has become one of the most informative real-world endpoints in dermatology. A drug that performs brilliantly in a randomized controlled trial but is discontinued by half of patients within a year in routine care is telling clinicians something important that trial data alone cannot capture. Conversely, a drug with modest trial results but strong drug survival may be quietly serving patients well over the long term.

Ustekinumab occupies a unique position in the therapeutic arsenal for hidradenitis suppurativa. Unlike adalimumab and secukinumab, the two biologics formally approved for the condition in the United States, ustekinumab is used off-label. The drug targets the p40 protein subunit shared by two signaling molecules, interleukin-12 and interleukin-23, thereby blocking a pathway involved in Th1 and Th17 immune responses that are thought to drive inflammation in hidradenitis suppurativa. Ustekinumab is approved for psoriasis and psoriatic arthritis, and its favorable long-term safety profile and infrequent dosing schedule have made it an attractive option for dermatologists managing patients whose disease has failed other therapies. The typical dosing approach in hidradenitis suppurativa draws on the psoriasis regimen, with weight-based induction followed by maintenance injections, most commonly 90 milligrams every eight to twelve weeks depending on patient weight and clinical judgment.

The Ohio State research team designed their investigation as a retrospective cohort study, drawing on previously collected clinical data from patients treated at their institution. Retrospective designs of this kind are the workhorses of drug survival research because they allow investigators to follow patients across years of routine care rather than the compressed timelines of clinical trials. The study received approval from The Ohio State University Institutional Review Board under protocol number 2024H0433 and was conducted in accordance with the Declaration of Helsinki, with a waiver of individual patient consent granted because the analysis used previously collected, non-identifiable data. The work was supported in part by the Ohio State University College of Medicine Bennett Research Fund, reflecting the institutional investment in dermatologic outcomes research that such single-center studies require.

Methodologically, the researchers employed Kaplan-Meier analysis, the standard statistical technique for estimating survival probabilities over time when not all patients have completed follow-up. In this application, the survival curve tracks the proportion of patients still receiving ustekinumab at each time point after initiation. The supplementary materials accompanying the article reveal the granularity of the analysis: one Kaplan-Meier curve compares patients who were still on ustekinumab at the time of data collection with those who had already discontinued it, while another curve compares patients maintained on at least 90 milligrams every eight weeks for at least sixteen weeks against patients on lower dosing regimens over the same minimum period. That second comparison speaks directly to one of the most debated practical questions in biologic therapy for hidradenitis suppurativa, namely whether the doses validated in psoriasis are sufficient for a disease with a different inflammatory architecture, or whether patients benefit from more aggressive, shorter-interval dosing.

The dosing question matters because hidradenitis suppurativa is a heavier body-weight-associated disease than psoriasis in many respects, and biologic drugs can behave differently across body sizes. Fixed or weight-tiered dosing regimens developed for one indication do not always translate cleanly to another. If patients on the higher-intensity regimen of at least 90 milligrams every eight weeks demonstrate longer drug survival than those on more conservative schedules, that would suggest clinicians may be under-dosing a subset of patients who could otherwise sustain benefit. If the curves are similar, the finding would support the adequacy of standard dosing and spare patients the added cost and injection burden of escalation. Either outcome carries real consequences for how dermatologists individualize therapy, and the study’s framing around a minimum sixteen-week exposure period reflects an effort to distinguish genuine maintenance dosing effects from early discontinuations driven by primary failure.

The new study does not appear in a vacuum. Drug survival research in hidradenitis suppurativa has matured rapidly in recent years. A 2022 study published in JAMA Dermatology by Ring and colleagues examined drug survival across biologic classes in patients with the disease and established benchmark discontinuation rates that have been widely cited since. More recently, a systematic review and meta-analysis by Pham and colleagues published in the Journal of the American Academy of Dermatology in 2024 pooled drug survival data across biologic agents, giving clinicians a comparative framework. Adding to that picture, a 2025 cohort study by Young and colleagues reported that infliximab, an intravenous tumor necrosis factor inhibitor, showed superior drug survival among biologics for hidradenitis suppurativa, a finding that surprised some observers given the convenience advantages of self-injected subcutaneous agents. Against this backdrop, a dedicated analysis of ustekinumab fills an important gap, because the drug’s off-label status means it is often absent from registry-based comparisons that focus on approved therapies.

Why does drug survival vary so much between biologics in this disease? Several mechanisms are likely at play. Primary failure, in which the drug never controls the disease, may reflect that interleukin-12 and interleukin-23 signaling, while biologically plausible targets, are not the dominant drivers in every patient’s phenotype. Secondary loss of efficacy, in which a drug works initially and then fades, can involve antidrug antibody formation, although ustekinumab has a comparatively low immunogenicity profile relative to some other biologics. Adverse events, infections, and patient preference also shape the survival curves, as do systemic factors such as insurance prior-authorization requirements and the availability of newer alternatives, including the oral Janus kinase inhibitors that have recently entered the hidradenitis suppurativa treatment space. A drug survival analysis conducted at a single academic center captures all of these forces in the specific proportion that clinicians actually encounter in practice.

The limitations inherent to this study design deserve honest acknowledgment, and the authors’ choice of a research letter format signals an appropriately scoped contribution. Retrospective single-center cohorts are subject to selection bias, since the patients who receive off-label ustekinumab at a tertiary academic institution may differ systematically from the broader population of people with hidradenitis suppurativa. Sample size constraints can limit the statistical power of subgroup comparisons, particularly for Kaplan-Meier curves stratified by dosing intensity. Confounding by indication is another challenge: patients escalated to higher doses may have more severe disease, making it difficult to disentangle the effect of dosing from the effect of disease severity. The authors note that the underlying data are held in controlled access storage at The Ohio State University and are available from the corresponding author upon reasonable request, a transparency practice that supports future replication and pooled analyses.

For patients living with hidradenitis suppurativa, studies like this one translate into more informed conversations at the bedside. When a dermatologist weighs whether to start ustekinumab after adalimumab failure, or whether to push an ustekinumab dose to 90 milligrams every eight weeks rather than every twelve, real-world drug survival data provide the evidence base that package inserts and trial reports cannot. The research also underscores a broader trend in dermatology: the recognition that biologic therapy in hidradenitis suppurativa is a long-term commitment requiring longitudinal monitoring, dose individualization, and honest accounting of when drugs stop working. As the therapeutic landscape continues to expand, the accumulation of drug survival evidence across agents, doses, and patient subgroups will be essential to turning an expanding menu of options into genuinely personalized medicine. The Rousseau and Kaffenberger team’s contribution adds a carefully constructed data point to that growing body of knowledge, one that clinicians managing this challenging disease will be able to place alongside the JAMA Dermatology benchmarks, the 2024 meta-analysis, and the emerging comparative data on infliximab as they chart the best course for each patient.

Subject of Research: Drug survival and dosing of the biologic ustekinumab in patients with hidradenitis suppurativa

Article Title: Drug survival and dosing of ustekinumab in hidradenitis suppurativa

Article References: Drug survival and dosing of ustekinumab in hidradenitis suppurativa. (n.d.). https://doi.org/10.1007/s00403-026-04902-2

Image Credits: AI Generated

DOI: 10.1007/s00403-026-04902-2

Keywords: hidradenitis suppurativa, ustekinumab, drug survival, biologics, interleukin-12, interleukin-23, Kaplan-Meier analysis, retrospective cohort study, dosing regimens, dermatology, off-label therapy, real-world evidence

Type 2 diabetes is far more than a disorder of blood sugar. Persistent hyperglycaemia, insulin resistance and low-grade inflammation conspire to damage the endothelium, the delicate inner lining of blood vessels, setting the stage for atherosclerosis—the buildup of lipid-rich plaques that can rupture and trigger heart attacks and strokes. Oxidative stress and dyslipidaemia compound this damage. Even with modern glucose-lowering therapies, cardiovascular disease remains the leading cause of illness and death among people with type 2 diabetes, which is precisely why researchers are searching for biomarkers that capture the inflammatory dimension of risk beyond conventional lipid panels and glucose measurements.

The focus of the new study is a molecular oddity within the interleukin-12 family of cytokines. Interleukin-12, composed of the p35 and p40 subunits, is a potent driver of inflammatory immunity: it pushes naïve T cells toward the Th1 lineage and stimulates production of interferon-gamma, fuelling vascular inflammation and accelerating plaque formation. Interleukin-35, built from p35 paired with a different partner called Ebi3, does the opposite. Produced mainly by regulatory T cells and regulatory B cells, it suppresses effector immune responses and appears to protect blood vessels from injury. Because both cytokines incorporate the same p35 chain, measuring p35 in the bloodstream provides an integrated snapshot of the net balance between these opposing signals.

To test whether that balance relates to atherogenic risk, the team enrolled 80 adults with type 2 diabetes attending the Katutura Community Health Centre, diagnosing cases according to American Diabetes Association criteria. Participants were excluded if they had malignant disease, autoimmune disorders, pregnancy or recent infection, all of which could distort inflammatory readouts. Blood samples were analysed for full blood counts, erythrocyte sedimentation rate, glycated haemoglobin, fasting glucose, lipid profiles, C-reactive protein and globulins, while plasma p35 concentrations were quantified with a commercial enzyme-linked immunosorbent assay read at 450 nanometres. Patients were then split at the median p35 value of 18.48 picograms per millilitre into low and high groups of 40 each.

The two groups were remarkably well matched on the surface. Age, sex distribution, body mass index, blood pressure and disease duration were all comparable, with roughly 90 percent of the cohort being female. Yet beneath that apparent equivalence, striking metabolic differences emerged. Patients in the high-p35 group had significantly higher fasting glucose, averaging 10.71 versus 8.97 millimoles per litre, and a greater share of them—62.5 percent versus 42.5 percent—fell into the poor glycaemic control category defined by glycated haemoglobin above 8 percent. Most participants were on metformin, which the authors note may have dampened systemic inflammatory markers in both groups.

Indeed, standard inflammation measures told no story at all: C-reactive protein, erythrocyte sedimentation rate, the systemic immune-inflammation index, globulins and the neutrophil-to-lymphocyte ratio were statistically indistinguishable between groups. The lipid machinery, however, told a different tale. Triglycerides were markedly higher in the high-p35 group at 1.93 versus 1.24 millimoles per litre, high-density lipoprotein cholesterol was significantly lower at 0.97 versus 1.09 millimoles per litre, and the triglyceride-to-HDL ratio was substantially elevated. This pattern—more triglyceride-rich particles, less protective HDL—is precisely the profile that promotes lipid retention in arterial walls, foam cell formation and plaque growth.

Composite risk indices sharpened the picture further. The triglyceride-glucose index, a logarithmic measure of insulin resistance that integrates fasting triglycerides and glucose, averaged 9.63 in the high-p35 group versus 8.99 in the low group, with a striking 85 percent of high-p35 patients classified in the high-risk category above 9. The atherogenic index of plasma, calculated from triglycerides and HDL cholesterol, was more than six times higher in the high-p35 group, at 0.25 versus 0.04. Spearman correlation analysis confirmed that p35 levels rose in parallel with triglycerides, the atherogenic index, the triglyceride-to-HDL ratio and the triglyceride-glucose index, while showing a modest inverse relationship with HDL cholesterol. Notably, p35 showed no significant association with fasting glucose alone, suggesting the link runs through triglyceride-rich lipoprotein metabolism rather than glycaemia per se.

The relationship held up under statistical scrutiny. In a multiple linear regression model with the atherogenic index of plasma as the outcome, p35 remained an independent predictor alongside the triglyceride-glucose index, and the association persisted after adjusting for age, sex, body mass index, blood pressure, disease duration and medication use. Receiver operating characteristic analysis then tested whether p35 could actually discriminate high-risk patients: for identifying an elevated atherogenic index it achieved an area under the curve of 0.79, with an optimal threshold above 20.50 picograms per millilitre delivering 65 percent sensitivity and nearly 85 percent specificity, and a positive likelihood ratio of 4.30. Performance for detecting a high triglyceride-glucose index was similar, at an area under the curve of 0.78.

Mechanistically, the findings fit a coherent biological narrative. Excessive interleukin-12 signalling, transmitted through the JAK2-STAT4 pathway, promotes Th1 polarisation and interferon-gamma production, driving macrophage activation, adipose tissue inflammation and impaired insulin signalling—all of which feed insulin resistance and accelerate the transformation of macrophages into lipid-laden foam cells within plaques. Meanwhile, weakened interleukin-35 signalling from regulatory lymphocytes removes a brake on endothelial activation and leukocyte recruitment, allowing vascular inflammation to smoulder. Elevated triglycerides add their own insult through remnant lipoproteins that lodge in the arterial wall and through remodelling reactions that generate more atherogenic apolipoprotein B-containing particles while degrading the anti-inflammatory and cholesterol-efflux functions of HDL.

The authors are careful about the study’s central limitation: because p35 is shared, the assay cannot distinguish whether the signal reflects excess interleukin-12, deficient interleukin-35, or both. Prior studies have consistently reported elevated interleukin-12 in type 2 diabetes, whereas evidence on interleukin-35 remains inconclusive, so separate quantification of each cytokine is the logical next step. Unmeasured medications such as lipid-lowering agents and antihypertensives could also have influenced outcomes, and it remains unknown whether the association is specific to diabetes or reflects a general immune-metabolic response. Even so, the study’s strengths are considerable: a well-matched cohort, pre-powered sample size calculations, multivariable adjustment, and the use of composite indices that capture risk invisible to traditional lipid panels. If validated in larger and more diverse cohorts, a simple blood measurement of this shared cytokine subunit could become a practical immunometabolic tool for spotting cardiovascular danger in diabetic patients long before standard tests raise the alarm.

Subject of Research: The association between circulating IL-12/IL-35 p35 subunit levels and atherogenic risk in African patients with type 2 diabetes

Article Title: The Shared IL‐12/IL‐35 p35 Subunit Is Associated With Heightened Atherogenic Risk in African Patients With Type 2 Diabetes

Article References: Nyambuya, T. M., Shingenge, E., Ndevahoma, F., & Nkambule, B. B. (2026). The Shared IL ‐12/ IL ‐35 p35 Subunit Is Associated With Heightened Atherogenic Risk in African Patients With Type 2 Diabetes. Endocrinology, Diabetes & Metabolism, 9(5), Article e70306. https://doi.org/10.1002/edm2.70306

Image Credits: AI Generated

DOI: 10.1002/edm2.70306

Keywords: type 2 diabetes, interleukin-12, interleukin-35, p35 subunit, atherogenicity, cardiovascular risk, dyslipidaemia, insulin resistance, triglyceride-glucose index, atherogenic index of plasma, inflammation, Namibia