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Ixekizumab appears to provide significantly greater simultaneous joint and skin improvement for patients with psoriatic arthritis than adalimumab and doesn’t require combination with methotrexate to boost its efficacy.
Ixekizumab appears to provide significantly greater simultaneous joint and skin improvement for patients with psoriatic arthritis than adalimumab and doesn’t require combination with methotrexate to boost its efficacy, show the latest findings from the SPIRIT-H2H study.
An update on the results was provided at the annual meeting of the American College of Rheumatology in November, by investigator Josef Smolen, MD, from the Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.1 In this Q&A, Smolen, discusses the study’s wider findings.
The SPIRIT-H2H study is the first fully disclosed direct head-to-head study in psoriatic arthritis. The multicenter, open-label, blinded assessor study compared ixekizumab with adalimumab in biologic-naïve patients over 52 weeks. A total of 566 patients were randomized 1:1 to ixekizumab or adalimumab with stratification by concomitant conventional synthetic disease-modifying antirheumatic drug (csDMARD) use and presence of moderate-to-severe plaque psoriasis.
At 52 weeks, efficacy of ixekizumab and adalimumab was similar for 50% improved response on the American College of Rheumatology scale score (ACR50) (49.8% vs 49.8%, P =0.924), treat-to-target outcomes, enthesitis, and dactylitis resolution.2
However, a significantly higher proportion of patients treated with ixekizumab compared with those treated with adalimumab achieved PASI100 (64% versus 41%, P<0.001) or both ACR50 and Psoriasis Area and Severity Index (PASI) 100 (39% versus 26%, P<0.001).
Responses to ixekizumab were consistent irrespective of concomitant csDMARD use.
Significantly more patients on ixekizumab monotherapy versus adalimumab monotherapy achieved both ACR50 and PASI100 (38% vs 19%, P =0.007), and PASI100 responses (66% vs 35%, P<0.001).
No safety issues occurred with either ixekizumab or adalimumab.
In a subgroup analysis, subgroups were defined according to whether patients were treated with concomitant methotrexate at baseline.3 The results showed that levels of improvement with ixekizumab appeared to be similar regardless of concomitant methotrexate, whereas adalimumab efficacy appeared to be improved with concomitant methotrexate use. When used without concomitant methotrexate, ixekizumab resulted in significantly higher response versus adalimumab in terms of combined ACR50 and PASI100 (P = 0.002), minimal disease activity (P = 0.016), and very low disease activity (P= 0.037).
Rheumatology Network: What is the main take home message for rheumatologists?
Josef Smolen, MD: IL-17 inhibition with ixekizumab is at least as efficacious as adalimumab for all musculoskeletal manifestations and superior for skin changes. Ixekizumab appears to have similar efficacy whether it is used as a monotherapy or in combination with csDMARDs like methotrexate, while it appears that adalimumab has less efficacy as a monotherapy compared with combination therapy.
They should be reassured that IL-17 inhibition is efficacious and safe, in line with previous data and the license.
RN: Did anything surprise you about the findings?
Josef Smolen, MD: Overall TNF-blockade has been regarded as the gold standard for arthritis and enthesitis in psoriatic arthritis patients. The data from this head-to-head trial reveal that IL-17 inhibition has similar efficacy as TNF-inhibition. This is also true for remission by the Disease Activity Index for Psoriatic Arthritis (DAPSA), the optimal tool for psoriatic arthritis assessment.
Josef Smolen, MD: Treat-to-target is the way to go. Follow-up using the DAPSA provides an easy-to-use assessment possibility from start of treatment to target attainment. IL-17 inhibition is a good therapeutic option.
Hitherto head-to-head trials have been done in psoriasis but not in psoriatic arthritis. SPIRIT-H2H, to my recollection, was the first published trial comparing a newer compound with a TNF-inhibitor and it is the first that shows superiority of an IL-17 blocker for the primary endpoint. The analysis of the secondary endpoints also was in line with the assumptions.
RN: Should ixekizumab be used with or without ixekizumab?
Josef Smolen, MD: In general recommendations suggest to continue methotrexate and add biologic or targeted synthetic DMARDs, if the patient has tolerated methotrexate until this point in time. However, if methotrexate is not tolerated, then patients will benefit from ixekizumab monotherapy to a similar extent as with combination therapy.
1. ABSTRACT 0319. “Target Outcomes in Psoriatic Arthritis: Simultaneous Achievement of ACR50-Psoriasis Area and Severity Index 100 and Beyond: Insights from Open-Label, Assessor-Blinded Study at Week 24.” The annual meeting of the American College of Rheumatology. 9:00 AM, Friday, Nov. 6, 2020.
2. Smolen JS, Mease P, Tahir H, et al. Multicentre, randomised, open-label, parallel-group study evaluating the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naïve to biological disease-modifying antirheumatic drug: final results by week 52. Ann Rheum Dis. 2020;79(10):1310-1319. doi:10.1136/annrheumdis-2020-217372
3. Smolen JS, Sebba A, Ruderman EM, et al. Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Naïve Patients with Psoriatic Arthritis: 52-Week Results from SPIRIT-H2H Study. Rheumatol Ther. 2020;7(4):1021-1035. doi:10.1007/s40744-020-00250-3