Certolizumab pegol demonstrates ‘robust responses’ in patients with axial spondyloarthritis

Certolizumab pegol demonstrated continued improvements in disease activity during a 4-year period among patients with axial spondyloarthritis, according to data presented at the American College of Rheumatology Annual Meeting.

“Axial spondyloarthritis [axSpA] is an umbrella term for two diseases — ankylosing spondylitis [AS] and non-radiographic axial spondyloarthritis [nr-axSpA],” Atul A. Deodhar, MD, MRCP, FACP, FACR, of Oregon Health & Science University, told Healio Rheumatology. “Only ankylosing spondylitis has been approved by the FDA as a condition for which one can use tumor necrosis factor [TNF] inhibitors. We compared the response to TNF inhibitors among patients with ankylosing spondylitis with that of patients with non-radiographic axial spondyloarthritis.”

Atul A. Deodhar

Deodhar and colleagues examined 4-year data from the RAPID-axSpA trial, which demonstrated improvements in the signs and symptoms of axSpA during the span of 96 weeks. RAPID-axSpA was double-blind and placebo-controlled to Week 24. The trial was dose-blind to Week 48 and then followed an open-label design to Week 204. Patients met Assessment of Spondyloarthritis International Society (ASAS) Criteria and had active axSpA, with a positive sacroiliac joint MRI and/or raised C-reactive protein of greater than 7.9 mg/L.

Patients assigned to receive certolizumab pegol (Cimzia, UCB) 200 mg every 2 weeks or 400 mg every 4 weeks continued receiving the same dose in the open-label period. Deodhar and colleagues focused on efficacy data from patients originally assigned to certolizumab pegol as observed cases and with imputation, including non-responder imputation for categorical measures and last observation carried forward for continuous measures.

The analysis was completed using combined doses of certolizumab pegol. All patients treated with one or more doses of study drug were included in the safety set.

Two hundred and eighteen out of 325 patients were randomly assigned to treatment with certolizumab pegol from Week 0. Sixty-five percent of these patients (n = 142) completed therapy to Week 24. During the open-label period, 9.2% of patients withdrew from the study as the result of an adverse event and 1.4% withdrew because of lack of efficacy.

Ankylosing spondylitis (n= 81) was more common than nr-axSpA (n = 61). The number of patients who achieved ASAS20 and ASAS40 responses and partial remissions at Week 24 were maintained through Week 204. Improvements in all other clinical and patient-reported outcomes continued to demonstrate efficacy through Week 204, and investigators noted similar improvements in the AS and nr-axSpA groups. Results were observed in patients taking both doses of certolizumab pegol.

The responses among patients with AS and patients with nr-axSpA “were similar,” according to Deodhar.

“Patients with non-radiographic axial spondyloarthritis responded as robustly to certolizumab pegol as patients with ankylosing spondylitis,” he said.

Additional findings

The researchers also evaluated spinal mobility, function and enthesitis. Spinal mobility was measured with the linear Bath AS Metrology Index (BASMI), function was measured with the Bath Ankylosing Spondylitis Functional Index (BASFI) and enthesitis was measured with the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES). Mobility and function improved in both patient populations through Week 204; BASMI and BASFI scores were lower at Week 204 in patients with nr-axSpA, but those patients had less impairment at baseline, according to the study results.

Baseline enthesitis (MASES > 0) was reported in 148 patients. An increasing number of individuals in this group who remained on therapy through Week 204 attained complete enthesitis clearance (MASES = 0; observed case). This proportion was 39.6% at Week 12, 52.5% at Week 24 and 63.5% at Week 204. Among 52 patients with baseline heel enthesitis (defined as tenderness at proximal insertion of ≥1 Achilles tendon; observed case), investigators found 48% achieved clearance at Week 12; 65.3% at Week 24; and 74.3% at Week 204.

“The endpoints that we usually measure in these types of studies are ASAS20 and ASAS40,” Deodhar told Healio Rheumatology. “However, if you talk to the patient, what matters to them is fatigue, pain and function. Patient-reported outcomes are extraordinarily important, and they were all significantly improved in this study.”

Patients included in the safety set (n = 315) were exposed to certolizumab pegol for a total of 981 patient-years. The serious adverse event rate was 10.4 per 100 patient-years. Event rates for serious infections, malignancies and serious cardiovascular events were 2.3 per 100-patient years, 0.5 per 100-patient years and 0.4 per 100 patient-years, respectively. There were no deaths reported during the 4 years studied.

“Certolizumab pegol is an anti-TNF agent,” Deodhar said. “We are familiar with the safety issues for these, and this study was no exception. The rate of infections was similar to what we would expect in patients with ankylosing spondylitis treated with anti-TNF inhibitors.”

The most important finding of this study is the data regarding nr-axSpA, according to Deodhar.

“This is the first study to report on the use of TNF inhibitors for non-radiographic axial spondyloarthritis,” he said. “The FDA has not approved a single drug in the [United States] U.S. for this indication, but here we show that these patients have robust responses similar to the responses seen with ankylosing spondylitis.” – by Julia Ernst, MS

Reference:

Deodhar AA, et al. Abstract 687. Presented at: American College of Rheumatology Annual Meeting; Nov. 11-16, 2016; Washington.

Disclosures: Deodhar reports associations with AbbVie, Amgen, Boehringer Ingelheim, Eli-Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer and UCB. Please see the full study for a list of all other researchers’ relevant financial disclosures.