In an analysis of 12-month radiographic progression data from the double-blind, phase 3 OPAL BROADEN trial (ClinicalTrials.gov identifier: NCT01877668), elevated C-reactive protein (CRP) levels at baseline in patients with psoriatic arthritis (PsA) were associated with greater structural progression. In addition, treatment with either tofacitinib or adalimumab rapidly decreased the mean CRP concentration in patients with PsA, but the onset of CRP reduction was slower with tofacitinib 5 mg twice daily compared with tofacitinib 10 mg twice daily or adalimumab. Findings were published in The Journal of Rheumatology.
The investigators sought to assess the effect of baseline risk factors on radiographic disease progression in patients with active PsA and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) who were treated with tofacitinib or adalimumab. The coprimary end points were a ≥20% improvement in American College of Rheumatology criteria and the mean change in Health Assessment Questionnaire-Disability Index from baseline to 3 months.
All eligible patients were ≥18 years, had a PsA diagnosis for ≥6 months, met classification criteria for PsA, had an inadequate response to ≥1 csDMARDs, and had not previously received treatment with a tumor necrosis factor inhibitor. Participants were randomly assigned to 1 of 5 parallel treatment sequences: tofacitinib 5 mg twice daily (n=107), tofacitinib 10 mg twice daily (n=104), adalimumab 40 mg subcutaneous injection once every 2 weeks (n=106), placebo switched to tofacitinib 5 mg twice daily at 3 months, or placebo switched to tofacitinib 10 mg twice daily at 3 months. All participants received a stable background dose of a single csDMARD (methotrexate, sulfasalazine, or leflunomide) throughout the study and were followed for 12 months.
Radiographs that were obtained at baseline and 12 months were scored using the van der Heijde-modified Total Sharp Score (mTSS) for PsA. Radiographic nonprogression was predefined as a ≤0.5 increase from baseline in mTSS. Additional definitions of nonprogression included an increase from baseline in mTSS of ≤0 and ≤0.66. Changes from baseline in mTSS and nonprogression were analyzed by baseline CRP levels >2.87 mg/L or ≤2.87 mg/L.
Results of the study showed that at 12 months, >90% of participants treated with tofacitinib or adalimumab fulfilled all radiographic nonprogression criteria. Mean changes from baseline to 12 months in mTSS, erosion and joint space narrowing scores were close to 0. All changes in radiographic outcomes were minimal, regardless of baseline CRP levels, with a small numeric difference reported with tofacitinib 5 mg twice daily. Moreover, at 12 months, a significant relationship was observed between baseline CRP level and increases from baseline in mTSS >0.5 at 12 months.
Researchers noted that although new bone formation is a specific component of PsA, this phenotype was not evaluated by the mTSS method of scoring radiographs. Thus, the effect of tofacitinib or adalimumab on bone proliferation could not be analyzed in this study.
This study was funded by Pfizer Inc. For a full list of author disclosures, please see original article.
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 patients treated with tofacitinib or adalimumab [published online March 1, 2019].J Rheumatol. doi:10.3899/jrheum.180971