Continued Ixekizumab Therapy Proved More Effective Than Withdrawal in Patients With Psoriatic Arthritis

Patients with psoriatic arthritis (PsA) and minimal disease activity (MDA) who continued ixekizumab therapy fared significantly better than those who stopped using the drug, according to a study published in RMD Open.1 However, continuing ixekizumab following a relapse was shown to rapidly restore disease control.

“It is unclear whether patients in long-term low disease activity or remission need to continue treatment to maintain this outcome. Dose tapering or treatment discontinuation may potentially be cost effective and could limit potential side effects associated with PsA treatments,” investigators initially theorized.

In this multicenter, randomized, double-blind study, SPIRIT-P3 recruited adult patients with a confirmed diagnosis of PsA for 6 or more months who met the Classification Criteria for Psoriatic Arthritis (CASPAR). They were also required to have inadequate response or intolerance to at least 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD) and psoriatic skin lesions or a history of plaque psoriasis. The study was conducted in 12 countries at 86 sites.

Enrolled patients with PsA received 160 mg of ixekizumab, a high-affinity monoclonal antibody, at week 0, and then 80 mg every 2 weeks (IXE Q2W) for 36 weeks. Patients with sustained MDA for more than 3 months were then randomized 1:1 to either a blinded IXE Q2W withdrawal group and received a placebo between weeks 36-64, or continued treatment through week 104. Investigators analyzed time to relapse, or loss of MDA, for this patient group. If an individual in the withdrawal group relapsed, they were subsequently treated with IXE Q2W for the remainder of the study. The remainder of the patients (133) did not achieve MDA and continued on IXE Q2W.

The primary endpoint was the time to relapse for patients in the withdrawal cohort. Other endpoints included relapse rate and time and the time to regain and sustain MDA after retreatment in patients who relapsed during the withdrawal period.

Between November 18, 2015 and October 30, 2018, 394 biologic-naïve patients with active PsA were enrolled in SPIRIT-P3, of which 158 (40%) had achieved MDA and were placed in either the IXE Q2W withdrawal (N=79) or continued treatment (N=79) cohorts. Patients had symptoms for an average of 8 years, the mean age was 47 years, and 54% were female.

Investigators discovered that the withdrawal group relapsed in a significantly shorter time (median 22.3 weeks [95% CI 16.1-28.3]) as well as a higher proportion of patients who relapsed when compared with those who continued receiving ixekizumab. In the withdrawal group, 73% (58 of 79) patients relapsed, compared with only 34% (27 of 79) patients who continued IXE Q2W. Notably, when patients in the withdrawal cohort were able to continue treatment, the majority of patients were able to rapidly return to a state of MDA.

Further, 72% patients in the withdrawal cohort lost tender joint count (TJC), patient pain visual analogue scale (VAS) (90%), and global disease activity VAS (76%). The withdrawal cohort was more associated with greater loss in skin response (44% Psoriasis Area and Severity Index [PASI], 24% body surface area [BSA], p=0.0001) when compared with the IXE Q2W continued treatment group (12% PASI, 4% BSA).

Limitations of the study included the dosage of IXE Q2W, which is less than the current standard dose of every 4 weeks (IXE Q4W). However, the efficacy and safety of both doses are similar, so results are still clinically relevant. The study was focused on assessing treatment discontinuation, not reducing the dosage.

“Continued ixekizumab therapy was superior to withdrawal in maintaining MDA in biologic-naive patients with PsA who achieved sustained MDA on ixekizumab Q2W. Among patients who relapsed after ixekizumab withdrawal, the vast majority regained MDA after retreatment with ixekizumab Q2W,” concluded investigators. “These results indicate that continuous ixekizumab treatment is optimal for maintaining good disease control in PsA; however, patients can regain disease control after retreatment with ixekizumab in case of treatment interruption.”

Reference:

Swärdh E, Opava C, Brodin N. Physical activity in patients with rheumatoid arthritis - an agile lifelong behaviour: a qualitative meta-synthesis. RMD Open. 2021;7(2):e001635. doi:10.1136/rmdopen-2021-001635