Tocilizumab Treatment May Benefit Patients With Fibromyalgia

Patients with fibromyalgia may benefit from subcutaneous tocilizumab therapy, although a randomized controlled trial is needed to confirm efficacy, according to a study published in Biomedicines.¹

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The treatment efficacy of fibromyalgia is limited, and its pathogenesis remains elusive. However, researchers believe it involves immune dysregulation including pro-inflammatory cytokines, such as interleukin-6 (IL-6). Patients with other rheumatic diseases are also more likely to have a concomitant fibromyalgia diagnosis. Considering these factors, it is likely that the immune system plays an important role in the fibromyalgia-related symptoms of this patient population.²

“To date, the benefits of fibromyalgia treatments are modest, often with questionable clinical relevance,” wrote a group of Taiwanese investigators. “Tocilizumab, a humanized monoclonal antibody against IL-6 receptor, has been shown to be effective against a variety of inflammatory diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still’s disease, giant cell arteritis and Takayasu arteritis. Nevertheless, clinical studies on IL-6 inhibition in fibromyalgia patients are basically unavailable.”

Investigators reported a case series of patients with fibromyalgia receiving tocilizumab treatment. Symptoms were assessed using the revised Fibromyalgia Impact Questionnaire (FIQ), which evaluated pain levels, and the 2016 criteria of the American College of Rheumatology (ACR). Symptoms were compared using the Wilcoxon signed-rank test and neutrophiles from patients with fibromyalgia and matched controls were isolated for transcriptome analysis. Each patient underwent a 40-joint sonography at baseline, including the elbows, wrists, knees, ankles, metacarpophalangeal joints, and thumb interphalangeal joints.

A total of 2 primary and 4 secondary patients with fibromyalgia who received tocilizumab therapy for a minimum of 12 weeks between December 2020 and September 2022 were included in the analysis. Among patients, most (83%) were female, the median age was 51 years, disease duration was 3.5 years, and concomitant diagnoses were rheumatoid arthritis, hypereosinophilic syndrome, ankylosing spondylitis, and Sjogren’s syndrome. All patients reported severe symptoms regardless of standard treatment. Regarding treatment among the fibromyalgia cohort, 4 received subcutaneous tocilizumab 162 mg every 2 weeks and 2 received the same dose every 4 weeks.

The FIQ and general fibromyalgia symptoms improved at both 4 and 12 weeks with 4 (67%) patients achieving a pain reduction of ≥30% at the 4-week mark and 3 (50%) acheiving the same pain reduction at the 12-week mark. No significant changes in joint inflammation, as assessed by the 40-joint sonography, was observed.

Regarding adverse events, no infection was reported among all patients during the 12-week treatment period. However, an elevated level of low-density lipoprotein cholesterol in 1 patent receiving tocilizumab at week 12 was reported.

There were possible differentially expressed genes identified in primary patients when compared with controls after treatment with tocilizumab. Additionally, 2 genes upregulated in patients with fibromyalgia (C3ARI and PI3) when compared with matched health controls.

Investigators noted several limitations, including the small sample size. Additionally, the observational study design lent itself to potential placebo effects. The follow-up periods within the fibromyalgia cohort was relatively short and the improvement in symptoms may not be clinically significant. Therefore, investigators warned the therapeutic efficacy of tocilizumab is doubtful. Lastly, generalizability of results may be hindered as all patients were Han Chinese. Despite these limitations, the study sheds light on newer treatment options for patients with refractory fibromyalgia.

“Fibromyalgia is a distressful disorder, partly due to the modest therapeutic efficacy of the current treatment,” investigators concluded. “Our results unveiled the potential efficacy of subcutaneous tocilizumab on some refractory fibromyalgia patients.”

References

1. ^{Tang KT, Liao TL, Chen YH, Chen DY, Lai KL. Subcutaneous Tocilizumab May Be Effective in Refractory Fibromyalgia Patients. Biomedicines. 2023;11(7):1774. Published 2023 Jun 21. doi:10.3390/biomedicines11071774}
2. ^{Choy, E.H.; De Benedetti, F.; Takeuchi, T.; Hashizume, M.; John, M.R.; Kishimoto, T. Translating IL-6 biology into effective treatments. Nat. Rev. Rheumatol. 2020, 16, 335–345}