Treatment efficacy of certolizumab pegol was maintained for more than 4 years in patients with axial spondyloarthritis (axSpA) enrolled in the RAPID-axSpA clinical trial, according to a presentation at the 2016 European League Against Rheumatism Annual Congress. Certolizumab pegol is a monoclonal antibody to tumor necrosis factor (TNF)-α, said lead investigator Désirée van der Heijde, MD, Professor of Rheumatology, Leiden University Medical Center, The Netherlands. AxSpA is a chronic inflammatory disease characterized primarily by inflammation of the sacroiliac joints and spine, which leads to chronic back pain.
The RAPID-axSpA trial included patients with ankylosing spondylitis (radiographic-axSpA) and nonradiographic (nr-axSpA). RAPID-axSpA is the first long-term clinical trial investigating the continued benefit/risk profile of an anti-TNF agent to include such a broad axSpA group with both of these populations, Dr van der Heijde said in an interview. Some clinicians, especially in the United States, have maintained that nr-axSpA is a self-limiting disease, and that symptoms in these patients are likely to disappear without treatment. The inclusion of patients with nr-axSpA is noteworthy in that it allowed assessment of whether nr-axSpA is, in fact, self-limiting, Dr van der Heijde stated.
Treatment with certolizumab pegol in RAPID-axSpA was double-blinded and placebo-controlled for 24 weeks, dose-blinded to week 48, and open-label to week 204. All patients had active axSpA with positive sacroiliac joint magnetic resonance imaging, and/or increased C-reactive protein (>7.9 mg/L). Patients were originally randomized to receive certolizumab pegol (200 mg every 2 weeks, or 400 mg every 4 weeks), and continued with their assigned doses during the open-label period. The primary objective (ASAS20 [Assessment of SpondyloArthritis International Society 20] at week 12) was met, and has been previously presented.
Among the 218 patients randomized to receive certolizumab pegol from week 0, 93% completed to week 24, 88% to week 48, and 65% to week 204. Dr van der Heijde reported that among the patients completing 204 weeks of treatment, the completer proportions were similar in the axSpA and nr-axSpA subpopulations (67% vs 63%).
At week 204, ASAS20, ASAS40, and ASAS-PR [partial remission] were achieved in 54.1%, 44.0%, and 23.4% of patients, respectively, using nonresponder imputation (patients with missing data were considered to be nonresponders). In the patients with ankylosing spondylitis, ASAS20, ASAS40, and ASAS-PR were achieved in 56.2%, 44.6%, and 21.5%, respectively. In the patients with nr-axSpA, the rates were 51.5%, 43.3%, and 25.8%, respectively.
Mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score reductions were similar (last observation carried forward) for axSpA (–3.4) and nr-axSpA (–3.6) groups, as were Bath Ankylosing Spondylitis Functional Index (BASFI) score reductions (–2.6 and –2.7, respectively). Reductions were greater for BASDAI/BASFI in patients remaining on treatment (observed cases) in axSpA and nr-axSpA groups (–4.1 and –3.0), respectively.
Among patients remaining on treatment, responses to certolizumab pegol were maintained in a very high proportion, Dr van der Heijde commented. ASAS20, ASAS40, and ASAS-PR rates were 83.7%, 68.1%, and 36.5%, respectively, and, again, were similar in axSpA and nr-axSpA groups.
The 4-year safety profile for certolizumab pegol was consistent with previous reports of RAPID-axSpa results, with no new safety signals.
To investigate whether patients who withdrew from the study did so because of high disease activity, Ankylosing Spondylitis Disease Activity Score-inactive disease (ASDAS-ID) rates were compared between patients completing week 204, and patients withdrawing early (for whom ASDAS disease activity status at withdrawal was carried forward). At week 204, 31.0% of patients had ASDAS-ID, compared with 34.2% of those withdrawing early, suggesting that, in general, patients who withdrew did not do so because of an exacerbation in disease activity.
“For clinicians, these data show that efficacy is good after 4 years of treatment,” Dr van der Heijde emphasized. “The fact that response rates were very similar in patients with radiographic and nonradiographic disease sends an important message, that nr-axSpa is not a self-limiting disease.”
“The nr-axSpa data also show that patients who stopped treatment still have active disease. If the nr-axSpa were self-limiting, you would not see that,” she added.