Patients with sustained axial SpA remission can reduce, not discontinue, certolizumab pegol
Patients with early axial spondyloarthritis who achieved sustained remission at 48 weeks can reduce their maintenance dose of certolizumab pegol, although complete discontinuation should be avoided due to a high risk for flares, according to data published in the Annals of the Rheumatic Diseases.
“The high costs of TNF [inhibitors] and the possible consequences of long-term immunosuppression have raised the question of how remission, once achieved, should best be maintained,” Robert B.M. Landewé, MD, PhD, of the Amsterdam Rheumatology & Clinical Immunology Center, in the Netherlands, and colleagues wrote. “Trials in different systemic autoimmune diseases have explored remission induction-and-maintenance strategies.”
“Such strategies have not been formally tested in patients with axSpA, although previous studies have suggested that complete treatment withdrawal often leads to relapse,” they added. “Therefore, a key question remaining for clinicians is whether to maintain or reduce TNFi treatment in patients in whom sustained remission has been induced.”
To compare certolizumab pegol (Cimzia, UCB) dose continuation with reduction and withdrawal among patients with early axial SpA, Landewé and colleagues conducted the C-OPTIMISE study, a two-part, phase 3b multicenter trial of adults recruited from 108 sites between July 31, 2015, and March 24, 2017. Among the 1,253 patients screened, 736 were enrolled into the induction part of the study, including 407 with radiographic axial SpA and 329 with non-radiographic forms of the disease. During this 48-week, open-label induction period, participants received 200 mg doses of certolizumab pegol every 2 weeks.
At week 48, investigators randomly assigned participants who achieved remission — defined as an Ankylosing Spondylitis Disease Activity Score of less than 1.3 at weeks 32/36 and 48 —to one of three maintenance groups in the double-blind second part of the study. Those in the full maintenance group received 200 mg every 2 weeks, while the reduced maintenance group were treated with 200 mg every 4 weeks and the withdrawal group was given a placebo, all for an additional 48 weeks. The primary endpoint was the lack of flares through the double-blind part of the study.
According to the researchers, 323 participants achieved sustain remission, of whom 313 were randomized into one of the three maintenance groups, with 104 receiving the full dose, 105 treated with reduced dose and 104 receiving placebo. Among these participants, 83.7% of those in the full-dose group, and 79% of those in the reduced group, were free of flares during weeks 48 to 96, compared with 20.2% in the placebo group (P < .001). Findings were similar between participants with radiographic and non-radiographic axial SpA.
“In early axSpA patients in sustained remission after 1year of open-label treatment with [certolizumab pegol], reducing the maintenance dose of [certolizumab pegol] enabled patients to maintain their state of remission, while completely stopping treatment resulted in flares in the majority of patients,” Landewé and colleagues wrote. “[Certolizumab pegol] maintenance dose reduction is therefore a feasible option for the long-term management of this chronic rheumatic disease, which has the advantage of preserving the clinical benefits of remaining on TNFi treatment, reducing costs and limiting patients’ long-term exposure to immunosuppressive therapy.”