Remission is unlikely in non-radiographic axial spondyloarthritis without biologic therapy. Adding certolizumab to background therapy can lead to significant improvements in disease activity compared to placebo, researchers find.
In a recent article published in Arthritis & Rheumatology,Dr. Atul Deodhar, M.D., and colleagues have found that remission is unlikely in non-radiographic axial spondyloarthritis (nr-axSpA) without biologic therapy and that adding certolizumab to background therapy led to significant improvement in disease activity compared to placebo.
Axial Spondyloarthritis (axSpA) is a chronic inflammatory arthropathy mainly affecting the spine and subdivided into disease with radiographic evidence (ankylosing spondylitis [AS]) and without (non-radiographic axial spondyloarthritis [nr-axSpA]). First line treatment for axSpA consist of non-steroidal anti-inflammatory drugs (NSAIDs), conventional disease-modifying anti-rheumatic drugs (cDMARDs), steroids, and pain medicines. Tumor necrosis factor inhibitors (TNFi) have been employed for more severe active disease.
Nr-axSpA is less well described than ankylosing spondylitis and as such many patients with nr-axSpA go without TNFi treatment. The authors sought to determine the efficacy of the anti-TNF agent, certolizumab pegol (CZP) in the nr-axSpA population.
The authors conducted the C-axSpAnd trial, a three-year, phase III, multicenter, randomized, placebo controlled study looking at the efficacy and safety of CZP in patients with nr-axSpA. A 52-week parallel-group, double-blind model was utilized permitting optimization of non-biologic treatment over a lon timeframe to assess disease remission.
The primary outcome was efficacy defined as: Completing the study period, maintenance of double blind status, and achieving Ankylosing Spondylitis Disease Activity Score- Major Improvement (ASDAS-MI) at 52 weeks. Non-placebo treatment consisted of CZP administered via prefilled syringe given at a dose of 400mg at weeks zero, two and fourfollowed by 200 mg every two weeks. Background non-biologic drugs were continued.
In addition to disease activity, C-reactive protein (CRP) levels were collected. Secondary efficacy endpoints included several other established measures of disease activity. Logistic regression was utilized and odds ratios for the ASDAS-MI at week 52 were estimated.
Ultimately, 260 patients were included in the analysis. The primary endpoint, ASDAS-MI at week 52, was met by 47.2 percent (75/159) CZP with background patients and 7 percent (11/158) placebo with background patients (p<0.0001; odds ratio CZP plus NBBM vs. PBO and NBBM: 15.2.
By Week 52, 60.8 percent (96/158) placebo with background patients compared to 12.6% (20/159) CZP with background patients had switched to open-label treatment.
Significant improvements in all secondary measures were seen in the CZP plus background group including ASAS40 response, BASDAI, BASFI, nocturnal spinal pain, and SPARCC scores. There was no significant difference in post-baseline uveitis between groups. There were no significant differences between groups with regards to adverse events.
TAKE HOME POINTS AND FINAL THOUGHTS
The results of this well constructed and executed trial show that CZP is highly effective when combined with conventional background treatment in nr-axSpA with objective signs of inflammation. Uveitis flares were more common in the treatment group but not significantly so.
A particularly important point illustrated through placebo patients switching to open-label CZP suggest that nr-axSpA does not spontaneously remit and cannot be controlled with non-biologic medications. This point is further proven by the fact that only 11 of 158 placebo patients made it to 52 weeks and achieved ASDAS-MI.
The authors have uncovered a very important revelation in this study. Previously it was thought that nr-axSpA might be a self-limiting lesser evil compared to AS. As such treatment was far more conservative banking on the thought that it might just go away on its own at some point. By discovering that it is actually not likely to remit or improve dramatically with background therapy, the authors open the door for more aggressive treatment with TNFi drugs poised to give hope to nr-axSpA patients still suffering.
The shift in understanding about the course of nr-axSpA permitted by these results underscores the incredible value in randomized controlled investigations when compared to observational studies. Such a precision instrument protects clinicians inundated by hundreds of articles from the bias that seeps into the vast majority of them. This proves that taking the time to construct and properly power a trial can yield the type of results that can make a difference in the treatment strategies of SpA patients hopefully leading to improvements in their lives.
Atul Deodhar, MD, Lianne S. Gensler, MD, Jonathan Kay, MD, et al. A 52-week randomized placebo-controlled trial of certolizumab pegol in non-radiographic axial spondyloarthritis. Arthritis Rheumatol. 2019 Mar 8. doi: 10.1002/art.40866.