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Patients with psoriatic arthritis who achieved minimal disease activity on ixekizumab (Taltz) and continued on the drug fared better than patients who withdrew from treatment, an international randomized trial found.

Among patients who were randomized to treatment withdrawal after attaining a state of sustained minimal disease activity during open-label treatment with ixekizumab, the median time to relapse was 22.3 weeks (95% CI 16.1-28.3), whereas for those who continued on treatment, the median time until relapse was not estimable because fewer than 50% of patients had relapsed by the study's conclusion, reported Laura Coates, MD, of Oxford University in England, and colleagues.

In addition, the cumulative relapse rate during the first 40 weeks after randomization was 73% in the withdrawal group compared with 34% in the continuation group (P<0.0001), the investigators wrote online in .

Numerous effective agents are now available that can help patients with psoriatic arthritis reach a state of low or minimal disease activity, but it is as yet uncertain whether treatment withdrawal is possible for those with sustained responses.

Ixekizumab is a monoclonal antibody that targets interleukin-17A, and has demonstrated efficacy in two phase III trials, and . The current withdrawal study, known as SPIRIT-P3, was an additional phase III trial conducted at 86 sites in 12 countries from 2015 to 2018.

SPIRIT-P3 enrolled 394 patients with no prior biologic treatment who all underwent a 36-week open-label treatment period during which they were given a starting dose of 160 mg of subcutaneous ixekizumab and then 80 mg every 2 weeks.

Between weeks 36 and 64, patients who had been in sustained (more than 3 months) minimal disease activity were randomized to continue on 80-mg ixekizumab every 2 weeks or placebo until week 104.

Minimal disease activity was defined as having at least five of these criteria: Tender and swollen joint counts of 1 or less; Psoriasis Area and Severity Index (PASI) of 1 or less or body surface area of 3% or less; patient pain score of 15 or lower; patient global disease activity score of 20 or less; Health Assessment Questionnaire-Disability Index of 0.5 or lower; and no more than one tender entheseal point.

Of the patients, 74% completed the open-label phase, and 40% reached a sustained minimal disease activity state. The withdrawal and continuation groups each consisted of 79 patients.

Patients' mean age was 47, mean disease duration was almost 8 years, and most were receiving concomitant conventional disease-modifying anti-rheumatic drugs. Disease activity was considered high at baseline, with mean tender and swollen joint counts being 21 and 10, respectively, and more than 70% having enthesitis.

Time to relapse was significantly shorter in the withdrawal group on several of the individual components of minimal disease activity. Tender joint counts had risen above 1 in 72% during a median of 22.3 weeks in the withdrawal group compared with 48% during 64.3 weeks in the continuation group (P=0.0022). Swollen joint counts above 1 were seen in 45% of patients over a median of 28.7 weeks in the withdrawal group compared with 15% in the continuation group with a median time not estimable (P<0.0001).

Total PASI score had risen above 1 in 44% of patients after a median of 36 weeks in the withdrawal group compared with 12% of the continuation group with a median time not estimable (P<0.0001). Affected psoriasis body surface area over 3% was observed in 24% of the withdrawal group compared with 4% of the continuation group, again with median times to relapse not estimable (P=0.0001).

For pain, 90% of patients in the withdrawal group reported scores above 15 at a median time of 16.1 weeks compared with 42% of the continuation group with the median time not estimable (P<0.0001), and patient global disease activity scores above 20 were seen in 76% at a median of 20.6 weeks in the withdrawal group compared with 26% of the continuation group with median time not estimable (P<0.0001).

The median time to restoration of minimal disease activity when treatment was restarted following relapse was 4.1 weeks in the withdrawal group and 4.7 weeks in the continuation group. Median time to re-achieving minimal disease activity was 16.1 weeks in the withdrawal group and 28.1 weeks in the continuation group.

Safety was consistent with previous studies of ixekizumab, with two deaths occurring during the open-label phase -- one from accidental drowning considered unrelated to treatment and another from pneumonia, which was considered related to the study drug.

The results of the study "indicate that continuous ixekizumab treatment is optimal for maintaining good disease control in psoriatic arthritis; however, patients can regain disease control after retreatment with ixekizumab in case of treatment interruption," they concluded.

However, "it remains to be evaluated what patient and disease characteristics, including some potential biomarkers, may predict the outcomes of treatment discontinuation," they wrote.

A limitation of the study was the dosing regimen of 80 mg every 2 weeks, as the approved dose in the U.S. and Europe is every 4 weeks. "This study was started when the pivotal phase III studies in psoriatic arthritis were still ongoing, evaluating the safety and efficacy of ixekizumab at two dosing regimens: 80 mg every 2 weeks or every 4 weeks," the investigators explained.

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