Could adalimumab and its biosimilars become a less attractive option for treating some inflammatory diseases in the face of new therapeutic choices like interleukin-17 inhibitors? In the case of ixekizumab, a recent head-to-head study versus adalimumab showed that the newer product was superior in terms of improving joint and skin disease in patients with psoriatic arthritis.
Biosimilars of adalimumab have been a major success story in the European context, where their adoption following Humira’s loss of exclusivity in 2018 have led to substantial savings and increased patient access to treatment. But could adalimumab and its biosimilars become a less attractive option for treating some inflammatory diseases in the face of new therapeutic choices like interleukin-17 (IL-17) inhibitors? In the case of ixekizumab (Taltz), which targets IL-17, a recent head-to-head study versus adalimumab showed that the newer product was superior in terms of improving joint and skin disease in patients with psoriatic arthritis (PsA) who are naïve to biologic treatment.
The 52-week study in 566 patients with PsA was a phase 3b/4 randomized, open-label, parallel-group study evaluated the safety and efficacy of ixekizumab (n = 283) versus adalimumab (n = 283). All patients had an inadequate response to at least 1 disease-modifying antirheumatic drug (DMARD) and were naïve to both biologics and Janus kinase inhibitors.
Those randomized to ixekizumab received 80 mg every 4 weeks up to week 24 after a 160-mg starting dose at week 0. Those randomized to adalimumab received a 40-mg starting dose and 40 mg every 2 weeks up to week 24. Patients on either treatment who met criteria for moderate to severe PsA were eligible for higher doses. The primary end point was superiority of ixekizumab at week 24 as measured by proportion of patients who achieved both the criteria for an American College of Rheumatology 50% (ACR50) improvement and criteria for a 100% reduction in Psoriasis Area and Severity Index score (PASI100).
In total, 95% of the patients randomized to adalimumab and 93% of those randomized to ixekizumab completed the week 24 study visit.
The proportion of patients who achieved both ACR50 and PASI100 was 36% in the ixekizumab group versus 28% in the adalimumab group (P = .036), and the authors note that significant differences were observed as early as week 8. Ixekizumab was also noninferior to adalimumab in terms of ACR50 response (50.5% versus 46.6%, respectively), with a treatment difference of 3.9% (95% CI −4.3% to 12.1%). PASI100 response was significantly greater in the ixekizumab group than the adalimumab group (60% versus 47%, respectively; P = .001). Statistically significant differences in PASI100 were observed as early as week 4, and persisted through week 24.
Treatment-emergent adverse events (AEs) were more common in the ixekizumab group, and most were mild or moderate. Discontinuations due to AEs were numerically lower in the ixekizumab group. No deaths occurred in the study.
According to the authors, this study, the first head-to-head trial to compare 2 biologics in patients with active PsA who did not have an adequate response to conventional DMARDs, can help inform evidence-based treatment decisions for patients with PsA, particularly insofar as it mirrors real-world clinical practice in its design. The trial is ongoing through 52 weeks of treatment.
Mease 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 [published online September 28, 2019]. Ann Rheum Dis. doi: 10.1136/annrheumdis-2019-215386.