The Effect of Biological Treatment on Fatigue in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis

• Published in: Drugs (New York, N.Y.) N.Y.), 2023-07, Vol.83 (10), p.909-921
• Main Authors: Skjellerudsveen, Berit Mære, Skoie, Inger Marie, Dalen, Ingvild, Grimstad, Tore, Omdal, Roald
• Format: Article
• Language: English
• Subjects: Bias; Biological effects; Biological products; Biological treatment; Chronic illnesses; Clinical trials; Colitis, Ulcerative; Crohn Disease - complications; Crohn Disease - drug therapy; Crohn's disease; Drugs; Fatigue; Fatigue - drug therapy; FDA approval; Health risks; Health surveys; Humans; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - complications; Inflammatory Bowel Diseases - drug therapy; Internal Medicine; Intestine; Medicine; Medicine & Public Health; Meta-analysis; Patients; Pharmacology/Toxicology; Pharmacotherapy; Placebos; Quality of life; Randomized Controlled Trials as Topic; Systematic Review; Tumor necrosis factor-TNF; Ulcerative colitis
• ISSN: 0012-6667; 1179-1950
• DOI: 10.1007/s40265-023-01888-3

Background Fatigue is a frequent complaint in patients with inflammatory bowel disease. Biological drugs have demonstrated beneficial effects on some extraintestinal manifestations, but the effect on fatigue is not clear. Objective This study investigated the effects of biological and small molecule drugs approved for inflammatory bowel disease on fatigue. Methods We performed a systematic review and meta-analysis of randomized, placebo-controlled trials reporting Federal Drug Agency (FDA)-approved biological and small molecule drugs for use in ulcerative colitis and Crohn’s disease in which measures of fatigue were recorded before and after treatment. Only induction studies were included. Maintenance studies were excluded. We searched Embase (Ovid), Medline (Ovid), PsycINFO (Ovid), Cinahl (EBSCOhost), Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov in May 2022. Risk of bias was analyzed using the Cochrane risk-of-bias tool. Standardized mean difference was used to measure the treatment effect. Results A total of seven randomized controlled trials composed of 3835 patients were included in the meta-analysis. All of the studies included patients with moderately to severely active ulcerative colitis or Crohn’s disease. The studies used three different generic fatigue instruments: the Functional Assessment of Chronic Illness Therapy-Fatigue and the Short Form 36 Health Survey Vitality Subscale versions 1 and 2. Overall treatment with biological or small molecule agents showed a beneficial effect compared with placebo, with a standardized mean difference of 0.25 (95% confidence interval 0.15–0.34, p < 0.001). The effect was independent of type of drug or subtype of inflammatory bowel disease. Discussion The risk of bias was considered to be low for all domains except for missing outcome data. Even though the included studies were of high methodological quality, the review is limited by the small number of studies included and that the available studies were not designed to evaluate fatigue specifically. Conclusion Biological and small molecule drugs used in inflammatory bowel disease have a consistent, though small, beneficial effect on fatigue.