Long-Term Safety Associated with Use of Adalimumab for Ankylosing Spondylitis

Boston—There are 2 forms of axial spondyloarthritis (SpA): (1) ankylosing spondylitis (AS); and (2) nonradiographic axial SpA (nr-axSpA). Although patients with either form may be similar in demographics and disease activity, little information is available in the following areas: (1) extra-articular manifestations; (2) baseline comorbidities; and (3) the type and rates of adverse events in clinical trials of patients with either form of axial SpA.

A recent examination of 3 studies sought to look at these 3 areas in patients treated with AS or nr-axSpA who were administered adalimumab. The results were presented at the ACR/ARHP meeting during a poster session titled Comparison of Baseline Extra-articular Manifestations, Comorbidities, and Long-term Safety in Patients Treated With Adalimumab for Ankylosing Spondylitis and Non-radiographic Axial Spondyloarthritis.

The first study, the phase 3, randomized, double-blind, multicenter ATLAS trial, was conducted in the United States and Europe in patients with active AS who had an inadequate response to ≥1 nonsteroidal anti-inflammatory drug (NSAID) or were intolerant to NSAIDs.

Active disease was defined as fulfilling ≥2 of the following: Bath Ankylosing Spondylitis Disease Activity Index score ≥4 (scale is 1-10), total back pain ≥4 on a 0 cm to 10 cm visual analog scale, or duration of morning stiffness ≥1 hour.

The second study, the M03-606 phase 3, randomized, double-blind, multicenter trial, was conducted in Canada with the same study design as ATLAS.

The third study, the phase 3, multinational, randomized, double-blind, multicenter ABILITY-1 trial, was conducted in patients with active nr-axSpA who had an inadequate response or intolerance to at least 1 NSAID or contraindication for NSAIDs.

Patients were randomized to receive adalimumab 40 mg biweekly or placebo for 24 weeks followed by open-label adalimumab for up to 260 weeks in the ATLAS and M03-606 trials and for up to 156 weeks in the ABILITY-1 trial.

The any-adalimumab group consisted of patients who received ≥1 dose of adalimumab at any time during the study: ATLAS (n=311), M03-606 (n=82), and ABILITY-1 (n=183). A total of 393 patients had AS and 190 had nr-axSpA.

The mean age among participants with AS and nr-axSpA was similar, ranging from 37 to 42 years of age. AS patients were predominantly male, while the majority of nr-axSpA patients were female. At the time of the study, patients with AS had a longer mean disease duration compared with the nr-axSpA cohort. The mean duration of SpA symptoms was >10 years in the nr-axSpA group, though symptom duration was not collected in the AS studies.

In terms of extra-articular manifestations, at baseline uveitis and inflammatory bowel disease were less frequent in nr-axSpA patients compared with AS patients.

In terms of baseline disease activity, clinical measures of disease activity and pain were similar in both groups. Patient and physician global assessments of disease activity were similar between patients with AS and nr-axSpA. Elevated levels of C-reaction protein were more frequently observed in AS patients compared with the nr-axSpA population.

In terms of adverse events related to long-term use of adalimumab, the incidence of serious adverse events was similar in both populations. The malignancy rate was 0.8 events per 100 person-years for AS patients, while the malignancy rate was 0 events per 100 person-years for nr-axSpA patients.

Malignancies that were observed in the AS cohort included basal cell carcinoma (n=2), squamous cell carcinoma (n=3), malignant melanoma (n=1), non-Hodgkin’s lymphoma (n=1), colon cancer (n=1), gastric cancer (n=1), and metastatic ovarian cancer (n=1).

One death was reported in the AS group and 2 deaths were reported in the nr-axSpA group; none were considered related to adalimumab use.

The rate of new onset or worsening psoriasis was higher in the AS population, though the researchers indicated that this may be explained by the exclusion of comorbid psoriasis at baseline in the nr-axSpA population.

The researchers determined that the safety profile of adalimumab treatment was similar in all patients with axial SpA.—Kerri Fitzgerald

The study was sponsored by AbbVie.