The effectiveness of probiotics in the management of Inflammatory Arthritis

Abstract

Objective: To systematically identify, appraise and synthesis evidence of the formulation specific effects and population specific responses of probiotics in inflammatory arthritis (IA). Methods: MEDLINE (PubMed), CINAHL, EMBASE, and SCOPUS databases were searched for studies utilising probiotics and an intervention of inflammatory arthritis. The Joanna Briggs Institute (JBI) method was used to conduct the systematic review. A single reviewer undertook screening and data extraction. Two independent reviewers assessed the quality of evidence using JBI tools. Results: A total of 154 full text articles were retrieved and of these twelve eligible studies were reviewed. Of these, ten (83%) were randomised controlled trials and two (17%) were quasi-experimental studies. Four studies included a variety of spondyloarthopathies (SpA). Eight studies focused on rheumatoid arthritis (RA). Probiotics were supplied for a median timeframe of 60 and mode of 56 days (range 7-365 days). Overall, 17 different probiotics were supplied in colony forming units (CFU) per 24hrs ranging from 1x 108 to 2.25 x 1011. The genus of probiotic most commonly supplied was Lactobacillus. There was no statistical difference in the relative risk (RR) of minor adverse effects between probiotic and control groups (RR 1.02, 95% CI 0.69 to 1.51) when including nil event studies and no major adverse effects reported. However, effects were more often reported for studies on SpA. Meta-analysis identified a statistically significant benefit of probiotics on quality of life with a standard mean difference (SMD) effect size -0.37 (CI-0.59, -0.15), p=0.01 with subgroup analysis favouring Lactobacillus-only formulations. Negative effects sizes related to the reduction in quality of life scores that utilise a higher score to indicate worsening symptoms and more impact upon daily living. Small but statistically significant reductions in pain, p=0.006 with a mean difference effects size -8.97 (95%CI -15.38, -2.56), were identified independent of formulation. Meta-analysis confirmed the known statistically significant benefit of probiotics on the inflammatory marker C-reactive protein p=0.017 with a mean difference effects size -2.34 (95%CI -4.26, -0.41), with subgroup analysis demonstrating a greater difference in RA and combined Bifidobacterium and Lactobacillus formulations. The clinical significance of these small changes is questioned. Conclusion: This review indicates a potential differential benefit to combined formulations of Bifidobacterium and Lactobacillus compared to purely Lactobacillus formulations, with respect to reducing pain, lowering C-reactive protein and improving quality of life. It also suggests altered benefits dependant on the type of inflammatory arthritis with less benefit and more frequently reported side effects for individuals with SpA compared to RA. Generalisability of results to clinical practice is limited by the dominant demographic of older individuals, with established disease beyond the ‘therapeutic window of intervention’ for Inflammatory arthritis. Small but statistically significant benefits require confirmation using clinical studies with greater consideration to confounding factors of age, gender, diet and individual microbial signature.