番茄社区

Secukinumab (Cosentyx) was effective for axial manifestations of psoriatic arthritis in a 52-week multicenter phase III study, investigators reported.

The primary endpoint of a 20% response on the criteria of the Assessment of Spondyloarthritis International Society (ASAS20) at week 12 was met by 63% and 66% of patients randomized to subcutaneous secukinumab, 300 mg or 150 mg every 4 weeks, compared with 31% of those given placebo, according to Xenofon Baraliakos, MD, PhD, of Rheumazentrum Ruhrgebiet, Ruhr-University of Bochum in Germany, and colleagues.

Compared with placebo, the odds ratios of achieving ASAS20 responses were 3.8 (95% CI 2.4-6.1) and 4.4 (95% CI 2.7-7, P<0.0001) for the 300-mg and 150-mg groups, respectively, they reported online in .

Psoriatic arthritis is a heterogeneous inflammatory disorder that primarily affects the skin and nails and peripheral joints, but is also associated with enthesitis and dactylitis. The axial skeleton also may be involved, as in ankylosing spondylitis. "Although psoriatic arthritis and ankylosing spondylitis have a number of clinical features in common, ankylosing spondylitis accompanied with psoriasis and psoriatic arthritis with predominant axial involvement are considered two separate disease entities with overlapping features," Baraliakos and colleagues explained.

Moreover, criteria for axial psoriatic arthritis have not been clearly established; efforts are underway to develop suitable definitions by ASAS and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

In addition, in none of the clinical trials of biologics for psoriatic arthritis has there been a specific evaluation of the effects on axial disease.

Accordingly, the investigators conducted a trial that enrolled 498 patients from 97 centers from 2016 to 2018.

The study consisted of a 12-week placebo-controlled phase of 300 mg or 150 mg of secukinumab followed by re-randomization of the placebo group to one of the two active doses through week 52.

Spine and sacroiliac joint inflammation were assessed on MRI at baseline and weeks 12 and 52, and rated on the Berlin MRI score. Approximately 60% of patients had evidence of spinal inflammation at baseline.

Patients' mean age was 47, and males and females were equally represented. Symptom duration was 7 years, baseline total spinal pain score was 73, and 85% of patients reported nighttime awakening from back pain. Mean Berlin MRI scores were 1.5 and 1.7 for the total spine and sacroiliac joints, respectively.

A total of 85% of patients remained in the study through week 52.

At week 12, 40% of responses (ASAS40) were seen in 44% and 40% of the 300-mg and 150-mg secukinumab groups compared with 12% of the placebo group, with ORs for achieving that endpoint of 5.6 (95% CI 3.2-9.8) and 4.7 (95% CI 2.7-8.3, P<0.0001), respectively.

The least squares mean treatment difference compared with placebo in total Berlin score for the entire spine at week 12 was -0.4 in both secukinumab groups and -0.5 for the sacroiliac joints, which were statistically significant differences.

Among patients who were also receiving methotrexate, the ASAS20 rates were 67% for both secukinumab groups and 40% in the placebo group.

At week 52, ASAS20 responses were 81% for the 300-mg group and 80% for the 150-mg group. For those who initially received placebo, ASAS20 responses at that time point were 75% for those who had been re-randomized to secukinumab 300 mg and 80% for those given 150 mg.

At week 52, mean changes for spinal pain were -42.4 and -43.8 for the 300-mg and 150-mg groups, respectively, and -43.1 and -36.4 for the groups initially given placebo and then re-randomized to 300 mg or 150 mg.

Berlin MRI scores for both entire spine and sacroiliac joints also were sustained at week 52, "providing objective evidence of reduced inflammation," the authors noted.

Overall adverse event rates at week 12 were 39% and 36% in the 300-mg and 150-mg groups and 47% in the placebo group. Serious adverse events throughout the trial were reported in 6% of secukinumab-treated patients, and seven serious infections occurred. One case of Crohn's disease was reported in the 150-mg group, and three major adverse cardiovascular events occurred. One of the cardiac events was fatal ischemic cardiomyopathy in a male patient, age 70, with hypercholesterolemia and hypertension who was receiving 300 mg; this was not considered treatment-related.

This was the first randomized trial to address the unmet clinical need of axial involvement in psoriatic arthritis, and as such, represents "a valuable data set for the research efforts on the classification and outcome measures of axial psoriatic arthritis," according to the investigators.

A limitation of the study, they acknowledged, was the challenge of designing it without a recognized consensus on clinical and imaging criteria for the disorder.

Comment