Radiographic progression of structural joint damage in patients with active psoriatic arthritis treated with ixekizumab over 52 weeks
Presenters: van der Heijde D1, Okada M2, Lee C3, Shuler CL3, Rathmann S3, Amato D3, Lin CY3, and Mease P4
Affiliations: 1Leiden University Medical Centre, Leiden, the Netherlands; 2St. Luke’s International Hospital, Tokyo, Japan; 3Eli Lilly and Company, Indianapolis, IN; 4Swedish Medical Center and University of Washington, Seattle, WA
Background/Objective: Ixekizumab (IXE), an anti-interleukin-17A monoclonal antibody, was shown to be superior to placebo (PBO) in clinical responses and in inhibition of the progression of structural joint damage in patients with psoriatic arthritis (PsA) treated for 24 weeks. Here, we assessed progression of structural joint damage in PsA patients with IXE for up to 52 weeks.
Methods: Biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with active PsA (n=417) entered into SPIRIT-P1 (NCT01695239), a double-blind Phase III trial. Patients must have had at least one joint erosion on the hand and foot confirmed by central x-ray reading or have had a C-reactive protein level less than 6mg/L at screening. A total of 417 patients were randomized to IXE 80mg every two (Q2W; n=103) or four weeks (Q4W; n=107) following a 160mg initial dose, PBO (n=106), or adalimumab 40mg every two weeks (ADA; active reference arm; n=101) for 24 weeks. In the Extension Period (EXT; Weeks 24–52), patients on PBO and ADA were re-randomized (1:1) to IXEQ2W or IXEQ4W at Week 16 (inadequate responders) or Week 24; patients on ADA underwent a washout prior to IXE treatment. All patients were assessed for structural joint damage using the van der Heijde modified PsA Total Sharp Score (mTSS, 0–528 scale). Two readers blinded to timepoint scored X-rays at Weeks 0, 24, and 52 independently and clinical data (average of readers). The mTSS was excluded from the prespecified analysis if the radiograph was taken after the scheduled visit date. In a post-hoc analysis, mTSS from a radiograph taken after the scheduled visit date was interpolated and considered as observed data. Any missing data at Week 52, in either presentation, were imputed using a linear extrapolation if they had at least one post-baseline value.
Results: Of the patients who had active PsA at Week 0, 381 patients (91.3%) entered the EXT, with 374 (98.2%) having radiographs collected during the EXT. Week 52 mean (SD) mTSS change from baseline were 0.54 (2.11) and 0.09 (1.0) for patients randomized to IXEQ4W and IXEQ2W at baseline, respectively. Similarly, post-hoc analysis changes at Week 52 were 0.47 (1.9) and 0.09 (0.9) for the IXEQ4W and IXEQ2W groups, respectively. The majority of patients on IXEQ2W or IXEQ4W exhibited no structural progression through one year of IXE treatment. In patients who switched from PBO or ADA to IXE, the Week 52 mean change from baseline mTSS values scores ranged from -0.03 to 0.41.
Conclusion: Over a 52-week period, minimal changes in mTSS were observed in patients with PsA entering the EXT and treated with IXEQ2W or IXEQ4W.