Questions about the BE OPTIMAL trial – Authors' reply

Abstract

We thank Sogol Stephanie Javadi and colleagues for their interest in the phase 3 BE OPTIMAL study, which demonstrated the efficacy and tolerability of bimekizumab in biologic-naive patients with psoriatic arthritis.1McInnes IB Asahina A Coates LC et al.Bimekizumab in patients with psoriatic arthritis, naive to biologic treatment: a randomised, double-blind, placebo-controlled, phase 3 trial (BE OPTIMAL).Lancet. 2023; 401: 25-37Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar Concerning the efficacy results, Javadi and colleagues incorrectly state that this study showed superiority to adalimumab for 50% or greater improvement in the American College of Rheumatology response criteria (ACR50). Adalimumab was included as a reference group only and no statistical comparisons were made between adalimumab and bimekizumab. Moreover, the SPIRIT-H2H trial showed the superiority of ixekizumab over adalimumab only when considering a combined ACR50 and Psoriasis Area and Severity Index 100% improvement response. Ixekizumab was non-inferior to adalimumab for ACR50 responder rates (ixekizumab 50·5% vs adalimumab 46·6%; treatment difference 3·9%; p=0·338).2Mease PJ Smolen JS Behrens F et al.A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial.Ann Rheum Dis. 2020; 79: 123-131Crossref PubMed Scopus (160) Google Scholar We respectfully disagree that the choice of adalimumab in our trial design will have produced a more favourable outcome for bimekizumab. Furthermore, tumour necrosis factor inhibitors such as adalimumab have been recommended as a first-line therapy option for patients with psoriatic arthritis, so this is a relevant choice of comparator for this biologic-naive patient population.3Singh JA Guyatt G Ogdie A et al.Special article: 2018 American College of Rheumatology/National Psoriasis Foundation guideline for the treatment of psoriatic arthritis.Arthritis Care Res. 2019; 71: 5-32Crossref Scopus (174) Google Scholar Additionally, in the era of adalimumab biosimilars, we feel this is a timely and key comparison for decision makers, including clinicians and payers. Regarding the potential effects of oestrogen contraceptive use on efficacy, a formal analysis of this was not performed. We understand that sex distribution can affect outcomes in psoriatic arthritis trials;4Coates LC van der Horst-Bruinsma I Lubrano E et al.Sex-specific differences in patients with psoriatic arthritis: a systematic review.J Rheumatol. 2023; 50: 488-496Crossref PubMed Google Scholar however, sub-analyses of efficacy observed in different patient subgroups were beyond the scope of the study and are planned for future communications, for both BE OPTIMAL and its sister study, BE COMPLETE.5Merola JF Landewé R McInnes IB et al.Bimekizumab in patients with active psoriatic arthritis and previous inadequate response or intolerance to tumour necrosis factor-α inhibitors: a randomised, double-blind, placebo-controlled, phase 3 trial (BE COMPLETE).Lancet. 2023; 401: 38-48Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar We agree that increased diversity and representation in clinical trials in psoriatic disease is desirable. Indeed, underrepresentation of minoritised racial groups has been noted in trials of other inflammatory disease states.6Strait A Castillo F Choden S et al.Clinical trials in rheumatoid arthritis have inadequate racial/ethnic, gender and age diversity: a systematic review.Arthritis Rheumatol. 2019; 71 (abstr).1160Google Scholar In line with this, UCB Pharma has committed to increasing diversity in clinical trials, to advance health equity. IBM has received consulting fees and honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Cabaletta, Causeway Therapeutics, Celgene, Evelo, Janssen, Eli Lilly, MoonLake, Novartis, and UCB Pharma; and research support from BMS, Boehringer Ingelheim, Celgene, Janssen, Novartis, and UCB Pharma. JFM is a consultant or investigator for AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Pfizer, Novartis, Regeneron, Sanofi, Sun Pharma, and UCB Pharma. Bimekizumab in patients with psoriatic arthritis, naive to biologic treatment: a randomised, double-blind, placebo-controlled, phase 3 trial (BE OPTIMAL)Bimekizumab treatment had superior improvements in joint, skin, and radiographic efficacy outcomes at week 16 compared with placebo in patients with psoriatic arthritis who were naive to biologic DMARDs. The safety profile of bimekizumab, including the occurrence of fungal infections, was consistent with previous phase 3 studies in patients with plaque psoriasis, and with IL-17A inhibitors. Full-Text PDF Open AccessQuestions about the BE OPTIMAL trialIn their study on the effects of bimekizumab in patients with psoriatic arthritis who are naive to biologicals, Iain B McInnes and colleagues showed that bimekizumab had greater improvement in American College of Rheumatology criteria (ACR50) compared with placebo and adalimumab.1 Although the results are encouraging, clarification is needed for better generalisability. Full-Text PDF