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Cytopenias among patients with rheumatic diseases using methotrexate: a meta-analysis of randomized controlled clinical trials.
Vanni, KMM, Lyu, H, Solomon, DH
Rheumatology (Oxford, England). 2020;(4):709-717
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Abstract
OBJECTIVE To conduct a systematic literature review and meta-analysis to estimate the incidence of anaemia, leucopoenia, neutropenia and thrombocytopenia associated with MTX plus folic acid among patients with rheumatic diseases. METHODS We searched MEDLINE, PubMed and EMBASE through August 2016 for all randomized controlled clinical trials with a MTX monotherapy arm. We excluded randomized controlled clinical trials for cancer and included only double-blind studies that reported on haematologic adverse events. Studies were excluded if patients did not receive folic acid or leucovorin supplementation. Full text articles were assessed by two independent reviewers. Incidence estimates were calculated using random-effects models. RESULTS Of 1601 studies identified, 30 (1.87%) were included, representing 3858 patients; all had RA. Seventeen trials reported on anaemia (n = 2032), 17 reported on leucopoenia (n = 2220), 16 reported on neutropenia (n = 2202) and 12 reported on thrombocytopenia (n = 1507). The incidence for any anaemia was 2.55% (95% CI 0.60-5.47%), any leucopoenia 1.17% (95% CI 0.16-2.80%), any neutropenia 1.77% (95% CI 0.33-4.00%), and any thrombocytopenia 0.19% (95% CI 0.00-0.86%). Four cases of severe anaemia were reported, as defined by authors, along with three cases of severe neutropenia. No cases of severe leucopoenia, severe thrombocytopenia or pancytopenia were reported. CONCLUSION Cytopenias are an uncommon side effect of low-dose MTX with folic acid supplementation among RA patients. Further research is needed to reach a more precise estimate.
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Low-Dose Methotrexate and Mucocutaneous Adverse Events: Results of a Systematic Literature Review and Meta-Analysis of Randomized Controlled Trials.
Lalani, R, Lyu, H, Vanni, K, Solomon, DH
Arthritis care & research. 2020;(8):1140-1146
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Abstract
OBJECTIVE Methotrexate (MTX) increases the risk of alopecia and stomatitis, but the prevalence of these adverse events among rheumatic patients taking MTX is poorly defined. We conducted a systematic literature review and meta-analysis to estimate the prevalence of alopecia and stomatitis with MTX in rheumatic diseases. METHODS We searched PubMed, The Cochrane Library, and CINAHL databases for double-blind randomized controlled trials (RCTs) with an MTX monotherapy arm. Alopecia, stomatitis, and oral/mouth ulcers data were extracted. The quality of trials was assessed by 2 authors. We included trials published since 1990 that used at least 10 mg of MTX weekly, coadministered with folic or folinic acid. We estimated the prevalence using random-effects models because heterogeneity was anticipated. Two estimates of prevalence were included; the lower bound estimate included all trials (assuming no alopecia and stomatitis if not mentioned), and the upper bound estimate included only those that specifically described prevalence estimates of alopecia or stomatitis. RESULTS Of 3,954 studies identified, 20 RCTs were included, with a total of 24 MTX monotherapy arms, of which 10 reported the prevalence of alopecia (n = 1,113), and 21 reported stomatitis or mouth/oral ulcers (n = 2,056). The prevalence of alopecia was between 1.0% and 4.9%. The prevalence of stomatitis was between 5.7% and 8.0%. CONCLUSION This meta-analysis gives more precise estimates of mucocutaneous adverse events that occur in rheumatic disease patients taking MTX. These estimates will help inform patient decision-making regarding MTX.
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A systemic review and meta-analysis of the clinical efficacy and safety of total glucosides of peony combined with methotrexate in rheumatoid arthritis.
Feng, ZT, Xu, J, He, GC, Cai, SJ, Li, J, Mei, ZG
Clinical rheumatology. 2018;(1):35-42
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Abstract
To assess the efficacy and safety of the combination of total glucoside of peony (TGP) and methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). Randomized controlled trial (RCT) data on the traditional Chinese active component TGP combined with MTX vs. MTX alone for the treatment of RA was collected by searching the Pubmed, Embase, Cochrane Library, CNKI, VIP Journals database, and Wanfang database up to February 2017. Study selection, data extraction, data synthesis, and data analyses were performed according to the Cochrane standards. A total of eight RCTs involving 522 participants were included in this meta-analysis. Compared with MTX alone, the use of TGP combined with MTX exhibited better therapeutic effects for the treatment of RA (P = 0.004). In addition, TGP combined with MTX caused a more significant decrease in erythrocyte sedimentation rate (ESR) (P < 0.0001) and swollen joint count (SJC) (P < 0.00001). However, no significant differences were found in C-reactive protein (CRP) (P = 0.19), duration of morning stiffness (DMS) (P = 0.32), or tender joint count (TJC) (P = 0.23) between the two groups. In addition, adverse events were more frequently reported in the MTX monotherapy group than in the TGP and MTX combination group (P = 0.0007). Our study demonstrates that TGP combined with MTX is more effective than MTX alone for the treatment of RA. Nevertheless, the adverse effects of the combination of TGP and MTX need to be further assessed. Due to the poor methodological quality of included trials, well-designed, multi-center, and large-scale RCTs are necessary to draw a more definitive conclusion.