Data from the CONSUL trial provide insight into the effects of TNF inhibitor monotherapy compared against combination therapy with NSAIDs for blunting radiographic spinal progression in adults with radiographic axial spondyloarthritis.
Combination therapy with nonsteroid anti-inflammatory drugs (NSAIDs) and TNF inhibitors was not significantly superior compared to monotherapy with TNF inhibitors for blunting the progression of structural damage in the spine among patients with radiographic axial spondylarthritis (r-axSpA), according to data presented at the American College of Rheumatology Convergence 2022.
Named the CONSUL trial, results of the study demonstrate a strategy leveraging use of celecoxib and golimumab did not slow the progression of radiographic spinal progression over a 2-year period compared to golimumab alone among patients with r-axSpA.
“Reduction of clinical burden and prevention of disability can probably be best achieved by early and adequate treatment targeting both inflammation and new bone formation,” said Fabian Proft, MD, a rheumatologist and senior researcher at Charité Universitätsmedizin Berlin, in a statement from the ACR.
A multicenter, open-label, randomized controlled trial, the CONSUL trial was created to explore whether combination therapy with TNF inhibitors and NSAIDs might confer greater benefit for radiographic spinal progression in patients with r-axSpA based on previous research suggesting NSAIDs, specifically celecoxib, might delay progression. Enrolling patients from 21 sites in Germany, the trial randomized patients to combination therapy or monotherapy and radiographic progression in the spine in both treatment groups after 2 years of therapy was selected as the primary outcome of interest.
For inclusion in the trial, patients were required to have a clinical diagnosis of r-axSpA, high disease activity despite NSAID therapy, and at least 1 additional risk factor for radiographic progression. Overall, 180 patients enrolled and . As part of study protocol, all patients participated in a 12-week run-in phase where they received 50 mg of golimumab every 4 weeks. After this period, those with considered to have a good clinical response were randomized to the combination arm, where they received 400 mg a day in addition to golimumab or the golimumab control group for 96 weeks.
For the purpose of analysis, radiographic spinal progression was assessed as change in the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) after 108 weeks in the intent-to-treat population. A total of 157 patients were screened. Of these, 81.5% (n=128) were enrolled in the 12-week run-in phase. Among this cohort, 109 patients fulfilled inclusion criteria for the 96-week treatment period and were randomized in a 1:1 ratio, with 54 and 55 individuals randomized to combination and monotherapy, respectively.
Upon analysis, results suggest the mean mSASSS change at 108 weeks was 1.1 (95% CI, 0.2-2.0) among the combination therapy arm and 1.7 (95% CI, 0.8-2.6) among the monotherapy arm (P=.79). Further analysis demonstrates new syndesmophytes were observed among 11% in the combination arm compared to 25% in the TNF monotherapy arm in the opinion of the 3 independent readers chosen to evaluate the mSASSS (P=.12). Investigators pointed out a total of 14 serious adverse events were reported during the trail, with 7 occurring in the combination therapy arm, 5 occurring in the monotherapy arm, and 2 occurring during the trial’s run-in phase.
In the aforementioned statement from the ACR, investigators noted failure to reach statistical significance does not conclusively rule out benefit of combination therapy compared against monotherapy.
“We did not expect that,” Proft added. “[It might be possible that] the findings would have become statistically significant with a larger sample size or longer follow-up, such as four years. [But] based on our data, continuous treatment with NSAIDs in addition to a biologic DMARD solely to inhibit future radiographic progression cannot be generally recommended. However, the observed effect of a combined treatment might be relevant in patients with a high risk for radiographic progression or with residual symptoms despite biologic DMARD therapy.”
This study, “COmparison of the Effect of Treatment with NSAIDs Added to Anti-TNF Therapy versus Anti-TNF Therapy Alone on Progression of StrUctural Damage in the Spine over Two Years in Patients with Ankylosing Spondylitis (CONSUL): An Open-Label, Randomized Controlled, Multicenter Trial,” was presented at ACR Convergence 22.