AB0551 HIGH-DOSE ORAL THIAMINE TREATMENT AGAINST CHRONIC FATIGUE IN PATIENTS WITH RHEUMATOID ARTHRITIS. A RANDOMISED CONTROLLED CROSS-OVER TRIAL
Authors: N. Stidsen, E. M. Hauge, P. Bager, T. B. Laurberg
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Fatigue is a prevalent and debilitating symptom in rheumatoid arthritis (RA), affecting up to 40% of patients daily [1,2]. Current medical treatment and biopsychosocial interventions have limited effect on reducing fatigue amongst patients with RA and chronic fatigue (&gt;6 months) [3]. A randomised controlled trial in patients with quiescent inflammatory bowel disease has shown that a 28-day treatment with high-dose oral thiamine reduced chronic fatigue [4]. No trials on thiamine treatment against fatigue in patients with RA have been conducted. <h3>Objectives:</h3> The objective of this study was to investigate the efficacy of 4 weeks of high-dose oral thiamine as treatment against chronic fatigue in patients with RA. <h3>Methods:</h3> This study was a randomised, controlled, cross-over trial. We included patients with RA in remission or with low disease activity (Multi-Dimensional Health Assessment Questionnaire (MD-HAQ) &lt;1.3, 28-joint Disease Activity Score (DAS28) &lt;3.2, C-reactive protein (CRP) &lt;10 mg/L), and chronic fatigue (Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ) score ≥16 points and fatigue duration of ≥ 6 months). Patients were excluded if they had anaemia, vitamin D or B12 deficiency, hypo/hyperthyroidism, diabetes mellitus, and pregnancy. Participants were randomly allocated 1:1 to receive either A) high-dose oral thiamine (600-1800 mg/day) for 4 weeks followed by 4 weeks wash-out period, then 4 weeks of oral placebo or B) 4 weeks of oral placebo, followed by 4 weeks wash-out period, then 4 weeks of high-dose oral thiamine. During the trial fatigue was evaluated using BRAF-MDQ. The Primary outcome was a reduction of BRAF-MDQ score after 4 weeks of thiamine treatment. The sample size, set at 40 participants, was based on an expected change in BRAF-MDQ score of 7.43 points, representing the minimal clinically important difference (MCID) [5], a 5% significance level, and a power of 80% or higher. Data was first tested for carry over effect, followed by 2x2 cross over analysis. Paired parametric data was analysed using paired t-tests. <h3>Results:</h3> A total of 40 patients were enrolled in the study. After 4 weeks of high-dose oral thiamine the mean difference in BRAF-MDQ score was -4.8 points (95% CI: -6.9; -2.7). In comparison, the mean difference after placebo was -6.5 points (95% CI: -9.2; -3.8). No carry over effect was found and no significant difference in BRAF-MDQ score was observed between thiamine treatment and placebo (p=0.58) during the cross-over analysis. Stratifying for sex, age, change in thiamine concentration in the blood, or baseline BRAF-MDQ score yielded no significant results. <h3>Conclusion:</h3> We observed no significant difference in chronic fatigue measured with BRAF-MDQ when comparing 4 weeks high-dose oral thiamine treatment to placebo in patients with RA in remission or with low disease activity. <h3>REFERENCES:</h3> [1] Wolfe, F., et al., J Rheumatol, 1996. [2] Hewlett, S., et al., Arthritis &amp; Rheumatism, 2005. [3] Pope, J.E., RMD Open, 2020. [4] Bager, P., et al., Aliment Pharmacol Ther, 2021. [5] Dures, E.K., et al., Rheumatology (Oxford), 2013. <h3>Acknowledgements:</h3> Gigtforeningen, Denmark for funding. <h3>Disclosure of Interests:</h3> Nicoline Stidsen: None declared, Ellen-Margrethe Hauge Novo, Novartis, research funding to Aarhus University Hospital from Independent Research Fund Denmark, Novo Nordic Foundation, Danish Rheumatism Association, Aarhus University, Danish Regions Medicine Grants, Galapagos, AbbVie principal investigator in trials by SynACT Pharma and involved as site principal investigator in trials by AbbVie, Novartis, Novo Nordisk, Sanofi. All unrelated to this manuscript, Palle Bager: None declared, Trine Bay Laurberg: None declared.