1.
How does methotrexate work?
Alqarni, AM, Zeidler, MP
Biochemical Society transactions. 2020;(2):559-567
Abstract
Developed over 70 years ago as an anti-folate chemotherapy agent, methotrexate (MTX) is a WHO 'essential medicine' that is now widely employed as a first-line treatment in auto-immune, inflammatory diseases such as rheumatoid arthritis (RA), psoriasis and Crone's disease. When used for these diseases patients typically take a once weekly low-dose of MTX - a therapy which provides effective inflammatory control to tens of millions of people worldwide. While undoubtedly effective, our understanding of the anti-inflammatory mechanism-of-action of low-dose MTX is incomplete. In particular, the long-held dogma that this disease-modifying anti-rheumatic drug (DMARD) acts via the folate pathway does not appear to hold up to scrutiny. Recently, MTX has been identified as an inhibitor of JAK/STAT pathway activity, a suggestion supported by many independent threads of evidence. Intriguingly, the JAK/STAT pathway is central to both the inflammatory and immune systems and is a pathway already targeted by other RA treatments. We suggest that the DMARD activity of MTX is likely to be largely mediated by its inhibition of JAK/STAT pathway signalling while many of its side effects are likely associated with the folate pathway. This insight into the mechanism-of-action of MTX opens the possibility for repurposing this low cost, safe and effective drug for the treatment of other JAK/STAT pathway-associated diseases.
2.
Updated pharmacological management of rheumatoid arthritis for women before, during, and after pregnancy, reflecting recent guidelines.
Murray, KE, Moore, L, O'Brien, C, Clohessy, A, Brophy, C, Minnock, P, FitzGerald, O, Molloy, ES, Mongey, AB, Higgins, S, et al
Irish journal of medical science. 2019;(1):169-172
Abstract
BACKGROUND Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease which can cause significant disability, morbidity, mortality, and impaired fertility. It commonly affects women of childbearing age. Managing rheumatoid arthritis (RA) in the perinatal period poses challenges. There is concern about the teratogenic effects of many traditional disease-modifying anti-rheumatic drugs (DMARDs) and an ever-growing list of new therapeutic options with limited data in pregnancy and breastfeeding. AIMS We aimed to create a standardized approach to pharmacological management of RA patients seen in our newly established Rheumatology and Reproductive Health Service. METHODS We reviewed relevant publications on the use of anti-rheumatic drugs in pregnancy. These include recent guidelines from The British Society for Rheumatology (BSR) and British Health Professionals in Rheumatology (BHPR) and the European League Against Rheumatism (EULAR). RESULTS After considering relevant publications, we developed a Saint Vincent's University Hospital/National Maternity Hospital consensus protocol for evidence-based medication in pregnancy in RA. CONCLUSIONS RA tends to improve during pregnancy and flare postpartum. Several anti-rheumatic medication options during pregnancy and breastfeeding are now available including anti-tumor necrosis factor (anti-TNF) agents. Good disease control at all stages of reproduction is important to ensure best outcome for both mother and baby.
3.
The therapeutic effect of probiotics on rheumatoid arthritis: a systematic review and meta-analysis of randomized control trials.
Mohammed, AT, Khattab, M, Ahmed, AM, Turk, T, Sakr, N, M Khalil, A, Abdelhalim, M, Sawaf, B, Hirayama, K, Huy, NT
Clinical rheumatology. 2017;(12):2697-2707
Abstract
Rheumatoid arthritis is an autoimmune disease in which probiotics appears to have an immune modulating action along with decreased inflammatory process. Therefore, we aim to investigate the efficacy of probiotics as an adjuvant therapy for rheumatoid arthritis. A comprehensive literature search was performed using nine databases including PubMed and Web of Science. Interesting data was extracted and meta-analyzed. We assessed the risk of bias using Cochrane Collaboration's tool. The protocol was registered in PROSPERO (CRD 42016036769). We found nine studies involving 361 patients who met our eligibility criteria. Our meta-analysis indicated that pro-inflammatory cytokine IL-6 was significantly lower in the probiotics compared with the placebo group (standardized mean difference = - 0.708; 95% confidence interval (CI) - 1.370 to 0.047, P = 0.036). However, there was no difference between probiotics and placebo in disease activity score (mean difference 0.023; 95% CI - 0.584 to 0.631, P = 0.940). Probiotics lowered pro-inflammatory cytokines IL-6 in RA; however, its clinical effect is still unclear. Hence, many high-quality randomized controlled trials (RCTs) are still needed to prove this effect.