Apremilast as an Adjuvant in Refractory Reactive Arthritis: A Retrospective Observational Study

Background and objective Reactive arthritis (ReA), formerly termed Reiter's syndrome, is an autoimmune inflammatory arthritis that develops in response to a gastrointestinal or genitourinary infection. Although nearly two-thirds of patients have a self-limited course, the remaining patients go on to develop chronic symptoms and complications. In the absence of a curative treatment, the treatment goal remains the alleviation of symptoms, for which diverse treatments have been used with variable responses. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor typically used for psoriatic arthritis and plaque psoriasis, appears to be a promising therapeutic option for ReA. This study aimed to evaluate the efficacy and safety of oral apremilast as an adjuvant therapy in patients with treatment-refractory ReA. In this study, adjuvant therapy refers to the addition of apremilast to ongoing conventional treatment with the aim of improving disease control and facilitating the reduction or discontinuation of concomitant medications such as corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs). Material and methods This was a retrospective, observational pilot study conducted at a tertiary care center. Medical records of 12 adult patients with treatment-refractory ReA, defined according to the criteria of the Third International Workshop on Reactive Arthritis (1996), who received oral apremilast as adjuvant therapy for 40 weeks between June 2024 and May 2025, were reviewed. Apremilast was administered at a dose of 30 mg twice daily following one week of dose titration. Treatment efficacy was primarily assessed using the American College of Rheumatology 20% improvement criteria (ACR20) along with secondary outcomes including ACR50/70 responses, changes in swollen and tender joint counts, inflammatory markers, improvement in functional outcomes measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI) status, and evaluation of the corticosteroid-sparing effect.  Results The mean age of the patients at the time of diagnosis was 26.91 years (range 19-36 years). Of the patients receiving apremilast (n=12), 10 (83.33%) achieved an ACR20 response at week 40. Although observed in a smaller proportion of patients, the higher-efficacy outcome measures, such as ACR50 and ACR70 responses, were sustained over 40 weeks in eight (66.67%) and five (41.67%) patients with continued treatment. The mean swollen joint count (SJC) and tender joint count (TJC) improved by 79.3% and 68.8%, respectively, at week 40. Around two-thirds of the treated patients (n=8, 66.67%) achieved a HAQ-DI minimal clinically important difference of ≥0.35 at 40 weeks. No serious infections or any other severe adverse effects were recorded in any of the patients. Conclusions Apremilast appears to be an efficacious and safe novel therapeutic option for treatment-refractory ReA. In addition to providing direct and substantial improvements in joint-related symptoms and beneficial effects on extra-articular manifestations, its corticosteroid-sparing effect makes it a promising candidate as an adjuvant in the treatment of ReA. The results of this study warrant further validation in larger controlled trials.