MADRID – Tumor necrosis factor inhibitors are further solidifying their position as the go-to drug class for patients with spondyloarthritis who fail to adequately respond to treatment with nonsteroidal anti-inflammatory drugs.
Results from a series of reports at the annual European Congress of Rheumatology gave further support for the safety and efficacy of tumor necrosis factor (TNF) inhibitors for treating axial spondyloarthritis (SpA), and another report at the meeting provided some of the first evidence for efficacy of the TNF inhibitor class in patients with the less-studied variant, peripheral SpA.
Dr. Philip Mease
TNF inhibitors "work well for symptoms, and are the gold standard for treating active axial SpA," said Dr. Philip J. Mease, a rheumatologist at Swedish Medical Center in Seattle. He reported evidence for the efficacy of a TNF inhibitor in patients with peripheral SpA without psoriatic involvement, a form of SpA that he said is increasingly being diagnosed after it was first defined a few years ago. The study that Dr. Mease reported on was the first to use the diagnostic criteria for peripheral SpA published by the Assessment of Spondyloarthritis International Society (ASAS) in 2011 (Ann. Rheum. Dis. 2011;70:25-31). Although several TNF inhibitors now have labeling for treating axial SpA and psoriatic arthritis, none currently have U.S. approval for treating peripheral SpA.
The ABILITY-2 (Study of Adalimumab in Subjects With Peripheral Spondyloarthritis) study enrolled patients in the United States, Canada, and several European countries. Patients either had an inadequate response to at least two different nonsteroidal anti-inflammatory drugs (NSAIDs) or were intolerant of or had contraindications for these drugs. Study participants received either 40 mg of adalimumab (Humira) subcutaneously every other week or placebo for 12 weeks.
The study’s primary endpoint was the percentage of patients achieving the peripheral SpA response criteria 40 at 12 weeks, a composite endpoint that requires at least a 40% improvement on each of three measures: patient global assessment of disease activity; patient global assessment of disease pain; and swollen and tender joint count, enthesitis count, or dactylitis count.
The rate of patients fulfilling the primary endpoint was 39% in 84 patients treated with adalimumab and 20% in 81 patients on placebo, a significant difference. Treatment with adalimumab also was linked to "substantial" and statistically significant improvements after 12 weeks in physical function, health-related quality of life, and work productivity, Dr. Mease reported.
Reports on using TNF inhibitors to treat axial SpA at the congress included results from the first randomized, controlled, phase III trial of a TNF inhibitor to enroll patients from the full range of axial SpA, including roughly equal numbers of patients with ankylosing spondylitis and patients diagnosed with axial SpA but without radiographic changes. The phase III RAPID-axSpA (Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of Certolizumab Pegol in Subjects with Active Axial Spondyloarthritis) trial included 325 patients enrolled at 104 sites in the United States and several other countries. The study enrolled patients who had an elevated blood level of C-reactive protein, evidence of sacroiliitis on an MRI scan, or both, and had failed to adequately respond to treatment with at least one NSAID.
Researchers randomized patients to receive either 200 mg of certolizumab pegol (Cimzia) subcutaneously every 2 weeks, 400 mg of certolizumab pegol subcutaneously every 4 weeks, or placebo. All patients randomized to receive certolizumab pegol began with three subcutaneous loading doses of 400 mg administered at the study’s start and after 2 and 4 weeks. Currently, certolizumab pegol has no labeling for treating patients with axial SpA, unlike several other TNF inhibitors such as adalimumab and etanercept (Enbrel).
Dr. Joachim Sieper
The study’s primary endpoint was the percentage of patients achieving an ASAS 20 response after 12 weeks of treatment, which requires at least a 20% improvement in at least three of these four criteria: patient global assessment, spinal pain assessment, function, and inflammation. This endpoint was reached by 38% of the 107 placebo patients, 58% of the 111 patients who received certolizumab pegol every 2 weeks, and 64% of those who received certolizumab pegol every 4 weeks, showing statistically significant differences in favor of the active treatment, reported Dr. Robert B.M. Landewé at the congress.
Response rates were similar among the patients with ankylosing spondylitis and those with no radiographic pathology. After 24 weeks of treatment, the rate of ASAS 20 responders fell to 29% of the placebo patients, compared with increases to 67% of patients receiving certolizumab pegol every 2 weeks and to 70% in those getting the drug every 4 weeks.