Reduction in Rheumatoid Factor and Matrix Metalloproteinase-3 With Successful Glucocorticoid Withdrawal After Initiation of Pemafibrate in a Patient With Rheumatoid Arthritis and Hypertriglyceridemia: A Case Report.

Pemafibrate is a selective peroxisome proliferator-activated receptor α (PPARα) modulator (SPPARMα) used for hypertriglyceridemia. PPARα activation also suppresses nuclear factor-κB (NF-κB) signaling, a pathway central to synovial inflammation and joint destruction in rheumatoid arthritis (RA). Whether pemafibrate affects RA-related biomarkers in humans is unknown. A 51-year-old woman (height: 164 cm, body weight: 71 kg, body mass index: 26.4 kg/m²) with RA treated with methotrexate, bucillamine, iguratimod, and low-dose prednisolone (0.7 mg/day) had hypertriglyceridemia with coexisting metabolic dysfunction-associated steatotic liver disease (MASLD). Pemafibrate was started at 0.2 mg/day and increased to 0.4 mg/day after 12 weeks, while the disease-modifying antirheumatic drug (DMARD) regimen was kept unchanged throughout. Over the 20 months following the initiation of pemafibrate, rheumatoid factor (RF) and matrix metalloproteinase-3 (MMP-3) declined, and C-reactive protein (CRP) showed an overall decrease with a transient rise at month 6; prednisolone was tapered and discontinued after 17 months. The 28-joint Disease Activity Score based on C-reactive protein (CRP; DAS28-CRP), already in the remission range at baseline (1.9), remained below the remission threshold throughout. Serum triglycerides fell from 184 mg/dL to 88 mg/dL, and hepatic transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) showed a transient early increase followed by a return toward baseline, without meeting criteria for drug-induced liver injury. No adverse events attributable to pemafibrate were observed. In this patient, the introduction of pemafibrate was temporally associated with reductions in RA-related biomarkers and with successful glucocorticoid withdrawal, without any intensification of DMARD therapy. Because the baseline prednisolone dose was already low (0.7 mg/day), this withdrawal should be interpreted cautiously and should not be regarded as strong evidence of a glucocorticoid-sparing effect. Causality cannot be established from a single case; nevertheless, together with earlier clinical reports on fenofibrate, animal studies showing anti-arthritic effects of fenofibrate and bezafibrate, and preclinical evidence of PPARα-mediated NF-κB inhibition, this observation suggests that PPARα agonists merit further investigation as adjunctive agents in RA, particularly in patients with coexisting dyslipidemia or steatotic liver disease.