Belimumab in active systemic lupus erythematosus: added benefit for children and adolescents
Addendum with new conclusion / information subsequently submitted allows assessment of advantages
The monoclonal antibody belimumab has been approved since 2011 as add-on therapy in adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) with a high degree of disease activity despite standard therapy. In 2019, the approval was expanded to children aged five years and older and adolescents. The German Institute for Quality and Efficiency in Health Care (IQWiG) had therefore investigated in an early benefit assessment whether the drug offers an added benefit to these younger patients. The data submitted with the dossier were incomplete, however. In the commenting procedure, the drug manufacturer subsequently submitted information, which have now been appraised by IQWiG in the framework of an addendum. According to this addendum, there is a hint of a non-quantifiable added benefit.
Advantages in side effects
The analyses on the PLUTO study, which were the basis for the early benefit assessment, were not interpretable regarding morbidity and health-related quality of life; one of the reasons for this was that the proportion of children and adolescents who actually had high disease activity, as required by the approval, was unclear. The manufacturer addressed this aspect in its comments, which showed that the study was suitable for the early benefit assessment.
The data provided on side effects do not allow a fair comparison between treatment and comparator arm because the recording of side effects was ended prematurely in patients who required treatment escalation in the course of the study due to deterioration of disease-related symptoms. Side effects were therefore overlooked. However, since this was more common in the comparator arm, such exclusions were more likely to distort the results in favour of the comparator therapy. Despite this bias, side effects were less common under belimumab, so that the advantages of belimumab found in these outcomes were not called into question by the premature end of the observation. Overall, the advantage of belimumab is therefore due to the fact that children and adolescents with SLE have fewer side effects if they are treated with belimumab.
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 manufacturer’s dossier and the IQWiG dossier assessment, the manufacturer submitted additional information in the commenting procedure. The G-BA then commissioned IQWiG to assess the data subsequently submitted. IQWiG now presents this assessment in the form of an addendum. The G-BA makes a final decision on the extent of added benefit.