Inappropriate treatment in the control arm makes fair comparison impossible
The monoclonal antibody secukinumab is approved for the treatment of moderate to severe plaque psoriasis in children and adolescents from the age of six years who are candidates for systemic therapy. The German Institute for Quality and Efficiency in Health Care (IQWiG) now examined in an early benefit assessment whether the drug offers an added benefit for these patients in comparison with the appropriate comparator therapy (ACT). Since the drug manufacturer did not provide appropriate treatment to the participants in the control arm of the study on which its dossier was based, no fair comparison is possible. IQWiG therefore concluded that an added benefit is not proven.
Approval is broader than that of the comparator therapy
The approval of the new drug is broader than the approval of the ACT option chosen by the manufacturer, regarding both disease severity and line of treatment: Etanercept may only be used for the treatment of chronic severe plaque psoriasis in children and adolescents from the age of six years who are inadequately controlled by, or are intolerant to, other systemic therapies or phototherapies – but not in moderate disease severity or as the first systemic therapy after topical treatment.
Children in the etanercept arm continued treatment despite non-response
The manufacturer presented data from the CAIN457A2310 study, which includes two secukinumab arms with different dosages and, for comparison, one etanercept and one placebo arm. It used analyses after 52 weeks (end of the maintenance phase) in its dossier. There was another data cut-off after 24 weeks, for which no analyses were presented.
In case of non-response, children and adolescents in the placebo arm were switched to secukinumab after 12 weeks. For the other control arm – and thus for the ACT – there was no possibility of switching treatment, however: According to the Summary of Product Characteristics, etanercept treatment should be discontinued in patients who show no response after 12 weeks. In this study, treatment was continued in the entire arm until the end of the maintenance phase, although, according to the European Public Assessment Report, about one third of the patients did not respond to this therapy at the end of the 12-week induction phase (as measured by the Psoriasis Area and Severity Index [PASI 75]). These children and adolescents were thus deprived of switching to a possibly more effective therapy.
Regardless of response, etanercept was given for too long
According to the approval, the treatment of children and adolescents with etanercept should be ended after a total of 24 weeks. Continuing the therapy for another 28 weeks not only means that patients who do not respond to the treatment continue to receive ineffective therapy: Patients with good response are also put at risk of adverse events if they continue treatment. Continuous etanercept treatment beyond 24 weeks exceeds the maximum approved duration for all patients.
Katrin Nink from IQWiG’s Drug Assessment Department sums up the situation: “Hence, there are two reasons why the study is not suitable for assessing the added benefit of secukinumab in comparison with the appropriate comparator therapy. Treatment with etanercept after a non-response at week 12 no longer complies with the Summary of Product Characteristics – and if continued beyond 24 weeks, also does not comply with the approval for all patients. Apparently, not all children and adolescents in this control arm received appropriate medical care. This is not a fair comparison between secukinumab and etanercept.”
G BA decides on the extent of added benefit
The dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the Federal Joint Committee (G-BA). After publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.
More English-language information will be available soon (Sections 2.1 to 2.5 of the dossier assessment as well as easily understandable information on informedhealth.org). If you would like to be informed when these documents are available, please send an e-mail to [email protected]