Letter to the Editor: Short‐Term Effectiveness of Sulfasalazine and Tofacitinib in <scp>NSAID</scp> ‐Refractory Reactive Arthritis

We read with great interest the article by Mruthyunjaya et al. [1], titled “Short-Term Effectiveness of Sulfasalazine and Tofacitinib in NSAID-Refractory Reactive Arthritis”, published in the International Journal of Rheumatic Diseases. The authors should be acknowledged for addressing this clinically essential but understudied topic and providing vital data on therapy options in individuals with NSAID-refractory reactive arthritis. Their efforts to carefully evaluate the short-term effects of sulfasalazine and tofacitinib in a real-world population are timely and valuable. However, despite the significant insights this study gives, we believe it has the following limitations that deserve consideration. First, only 46 patients completed the study, all from a single hospital in India. This reduces the ability to generalize results to other populations. Results might not represent broader, more diverse patient groups. Rare adverse effects or subgroup responses may have been missed. A study found a significant difference in treatment effect estimates between single- and multi-center trials, suggesting that the evidence from single-center trials tends to exaggerate treatment effects [2]. Future research should be multi-center and recruit larger, more diverse cohorts. Second, the study uses a short follow-up duration of 12 weeks. However, reactive arthritis can become chronic; short follow-up may miss long-term relapse or side effects. Although estimates vary greatly, it is believed that 30%–50% of all instances of ReA become chronic, and the remainder recover autonomously within weeks to months [3]. Therefore, future studies should include follow-up of at least 6–12 months to determine the sustained benefits and better long-term safety of each drug. Third, while the authors acknowledge not ruling out Chlamydia-induced arthritis, they do not address the lack of stratification by other identified or suspected pathogens. Because different infections can trigger arthritis through different pathways, they may also respond differently to treatment. By grouping all patients together without analyzing them separately (enteric vs. genitourinary triggers or culture-positive vs. culture-negative), the study may have blurred the true effectiveness of the drugs. A study suggests that a 6-month course of combination antibiotics appears to be a successful therapy for persistent Chlamydia-induced ReA [4]. Future research should go beyond simply excluding Chlamydia and should actively identify the specific organisms involved. Fourth, allocation to SSZ (sulfasalazine) or TOF (tofacitinib) was observational, not randomized. Lack of blinding may influence subjective measures like pain, etc., influencing the reported outcomes. A systemic review and meta-analysis report that the trials without patient blinding may slightly exaggerate the desirable effects of treatment [5]. Future studies should use a randomized controlled design with blinded assessors to reduce the bias. In conclusion, while this study adds useful evidence to the limited literature on the management of reactive arthritis, concerns about sample size, short follow-up, lack of stratification by causative organisms, and lack of blinding should be considered when interpreting the results. We expect that future research will address these concerns through larger, multi-center randomized controlled trials with longer follow-up and pathogen-specific analyses, ultimately offering more reliable guidance for physicians. Ahmed Furqan Anjum conceived the idea and reviewed the original article. Garzeen Ghaffar performed the literature search, drafted the manuscript, and reviewed and approved the final version of the article. The authors have nothing to report. The authors have nothing to report. The authors declare no conflicts of interest. The authors have nothing to report.