Among patients with psoriatic arthritis (PsA), elevated baseline C-reactive protein (CRP) has been associated with greater structural progression, particularly among patients who had an inadequate response to treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). This is according to research published in the Journal of Rheumatology.
Researchers conducted a post-hoc analysis of the results of the OPAL (Oral Psoriatic Arthritis triaL) Broaden study (ClinicalTrials.gov identifier NCT01877668), a randomized, 12-month, placebo-controlled, double-blind, multicenter, phase 3 examination of the safety and efficacy of treatment with tofacitinib or adalimumab in PsA. Investigators sought to examine the relationship between prognostic factors for radiographic progression and radiographic outcomes of participants in the OPAL Broaden study through evaluation of the presence of elevated CRP, swollen joints, dactylitis, PsA duration, and level of disease activity.
The researchers analyzed data from the following 3 OPAL Broaden study groups: tofacitinib 5 mg twice daily (n=107), tofacitinib 10 mg twice daily (n=104), and adalimumab 40 mg once every 2 weeks (n=106). At 12 months, 96.6% (n=282) of patients had complete radiographic data.
Researchers used the van der Heijde-modified total Sharp score (mTSS) for PsA to evaluate changes in 98, 99, and 95 patients from each group, respectively. Baseline changes in mTSS and radiographic nonprogression, defined as an increase of ≤0.5, ≤0, or ≤0.66 from baseline mTSS, were analyzed via baseline CRP >2.87 or ≤2.87 mg/l.
At 12 months, more than 90% of patients receiving either treatment met all criteria for radiographic nonprogression. Mean changes in mTSS, erosion, and joint space narrowing scores were close to 0, and the researchers identified minimal changes in radiographic outcomes, regardless of baseline CRP level.
In a linear regression analysis, no significant relationships were observed between any risk factors at baseline and mTSS scores at month 12. However, a logistic regression analysis found a significant relationship between baseline CRP and baseline mTSS <0.5 increases (regression coefficient, 0.023; 95% CI, 0.003-0.042 and odds ratio, 1.02; 95% CI, 1.00-1.04; P =.023).
Investigators noted several limitations of their analysis, in particular that the OPAL Broaden study was “not designed to compare active treatment versus placebo for assessment of radiographic outcomes.” Patients in the analysis were receiving active treatment in the form of either tofacitinib or adalimumab.
The researchers concluded that “Understanding which patients may be at increased risk for radiographic progression is important for achieving treatment goals to minimize structural damage.” Furthermore, “The identification of a significant relationship between baseline CRP levels and structural progression in patients with PsA who were treated with tofacitinib or [adalimumab] suggests an important role for CRP and inflammation in radiographic progression.”
Disclosure: This study was funded by Pfizer Inc., which manufactures tofacitinib. Pfizer was involved in the design of the study, the collection, analysis, and interpretation of the data, and the review and approval of the manuscript. Drs Graham, Wang, and Fallon are employees and shareholders of Pfizer, Inc. Drs Gladman and FitzGerald report the receipt of research grants and consultancy fees from various companies including Pfizer, Inc. For a complete list of disclosures, please refer to the full reference.
Van der Heijde D, Gladman DD, FitzGerald O, et al. Radiographic progression according to baseline C-reactive protein levels and other risk factors in psoriatic arthritis treated with tofacitinib or adalimumab [published online March 1, 2019]. J Rheumatol. doi:10.3899/jrheum.180971