Effects of Shuhe granules on chronic pain in patients with rheumatoid arthritis and fibromyalgia: a randomized, double-blind, placebo-controlled trial

Background Patients with rheumatoid arthritis (RA) and concomitant fibromyalgia (FM) frequently experience severe, refractory pain, elevated disease activity scores, and substantial psychological distress. Conventional treatments frequently fail to adequately address this complex pain syndrome, and evidence-based traditional Chinese medicine (TCM) interventions for this specific comorbidity remain limited. This pilot study aimed to assess the feasibility of a definitive trial and preliminarily evaluate the efficacy and safety of Shuhe granules (SHG), a Chinese herbal formulation, for alleviating chronic pain and associated multidimensional symptoms in this patient population. Methods In this randomized, double-blind, placebo-controlled pilot trial, 30 patients diagnosed with both RA and FM were randomly assigned (1:1) to receive either SHG (n = 15) or matching placebo (n = 15) twice daily for 4 weeks, followed by an 8-week follow-up. The primary outcome was the change in pain intensity measured by visual analog scale (VAS). Secondary outcomes included patient and physician global assessments (PGA, PhGA), tender and swollen joint counts (TJC, SJC), FM-specific measures (WPI, SSS, FIQ), and assessments of fatigue, sleep quality, anxiety, and depression. Safety was monitored through adverse event recording and laboratory tests. Results Twenty-six patients completed the trial (placebo completers n = 11 vs. SHG n = 15). Linear mixed-effects models showed significant group × time interactions for VAS ( P < 0.001), PGA and PhGA ( P < 0.001), and TJC ( P < 0.001). Within the SHG group, VAS scores showed a clinically meaningful reduction at week 4 ( P < 0.001), while no significant change occurred in the placebo group during the same period. TJC improvements persisted to week eight in the SHG group ( P < 0.001). For FM-related outcomes, significant group × time interactions were observed for SSS ( P < 0.001) and PHQ-9 ( P < 0.001), with the SHG group achieving clinically meaningful improvements in SSS at week 4 ( P < 0.001) and significant reductions in PHQ-9 ( P < 0.001). Although within-group improvements were also observed for FSS and ISI, between-group differences were not statistically significant. No serious adverse events occurred, and laboratory parameters remained within normal ranges for all participants. Conclusion This pilot study provides preliminary evidence that SHG may offer short-term benefits in reducing pain and improving physical function, sleep, fatigue, and psychological wellbeing in patients with RA and comorbid FM, with a safety profile comparable to placebo. While these preliminary findings support the potential of SHG as a therapeutic option, they require confirmation in larger, multicenter trials with extended follow-up to establish definitive efficacy and explore underlying mechanisms. Clinical Rehabilitation Impact SHG may represent a promising complementary therapy for relieving chronic pain and improving overall health in patients with RA complicated by FM. Larger, multicenter trials with extended follow-up are warranted to confirm these findings, explore underlying mechanisms, and define its role in integrative management strategies. Clinical Trial Registration Chinese Clinical Trial Registry (ChiCTR), https://www.chictr.org.cn/showproj.html?proj=221912 , Identifier ChiCTR2400081980.18 March 2024.