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BACKGROUND: Methotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared to thiopurines. AIMS: To review the efficacy, safety, optimal dosing and delivery regimens of methotrexate in adults with IBD. METHODS: We conducted a systematic review of studies involving patients with IBD treated with methotrexate from inception to August 2023. All studies were included from the MEDLINE database via PubMed. RESULTS: For Crohn's disease, we included eight randomised controlled trials (RCTs) and 17 observational studies. Parenteral methotrexate effectively increased remission rates in steroid-dependent patients at 25 mg/week for 16 weeks and at 15 mg/week for maintenance. Methotrexate can be used in combination with anti-tumour necrosis factor (TNF) agents to reduce immunogenicity. Data comparing thiopurines and methotrexate remain scarce. For ulcerative colitis (UC), we included five RCTs and 10 observational studies were included; there was no evidence to support the use of methotrexate in (UC). We extracted safety data from 17 studies; mild-to-moderate adverse effects were common. The incidence of liver fibrosis or cirrhosis was low. CONCLUSION: Methotrexate is effective at inducing and maintaining remission in steroid-refractory Crohn's disease and can reduce anti-TNF-induced immunogenicity when used in combination therapy. Data regarding tolerance and safety are reassuring. These findings challenge preconceived ideas on methotrexate and suggest that it is a valid first-line conventional option for the treatment of mild-to-moderate Crohn's disease.
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Background: We aimed to evaluate the value of the Fibrosis-4 (FIB-4) score as a prognostic factor in RA in the prospective ESPOIR cohort. Methods: We included patients from the ESPOIR cohort with a diagnosis of RA according to ACR/EULAR criteria. The formula for the FIB-4 score is as follows: [age (years) × aspartate transaminase level (U/L)]/[platelet count (109/L) × alanine aminotransferase level (U/L)1/2]. We used a linear mixed-effects model with a random effect of patient to account for repeated measures over time. Results: Overall, 647 of the 813 patients included met the ACR/EULAR criteria for RA, with no differential diagnosis during the first 10 years of follow-up. Of these patients, at baseline, 633 had a calculable FIB-4 score. Median FIB-4 score was 0.75 (interquartile range 0.53-0.99). On multivariate analysis, FIB-4 score was not independently associated with progression of Disease Activity Score in 28 joints over 10 years of follow-up, unlike baseline C-reactive protein level and SJC. Baseline FIB-4 score was not associated with the modified Sharp score at 5-year follow-up, unlike age and ACPAs. FIB-4 score was not associated with mortality (hazard ratio 1.1 [95% CI 0.46; 2.8], p = 0.77) or major adverse cardiovascular events (0.46 [0.13; 1.6], p = 0.22) over the 10-year follow-up. No significant change in FIB-4 score over time was related to treatments. Conclusions: The present prospective cohort study did not find a prognostic role of FIB-4 score in RA. Reassuringly, FIB-4 score was not increased with DMARD treatment after 10 years of follow-up.
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OBJECTIVES: We aimed to compare clinical spectrum and outcome between adults and children with Takayasu's arteritis (TAK) in a European population. METHODS: We made a nationwide retrospective observational study between 1988 and 2019. All adult patients met the ACR diagnostic criteria for TAK and all children met the EULAR/PRINTO/PRES criteria for paediatric TAK. RESULTS: We identified 46 children and 389 adults with TAK. The male to female ratio was 34/46 (0.74) in the paediatric group compared to 241/274 (0.88) in the adult group (P<0.05). Children presented with significantly more systemic symptoms; i.e., fever (P<0.05), fatigue (P<0.001), weight loss (P<0.001), abdominal pain (P<0.05), and myalgia (P<0.05) while adults had more upper limb claudication (P<0.01). Topography of the lesions differed significantly between the two groups: adults had more damage at the cerebral vasculature (P<0.01), upper and lower limbs (P<0.001) while children had more kidney lesions (P<0.05). Children TAK had more frequent (P<0.01) and higher (P<0.001) biological inflammation than adults. Children received higher dose-weight of corticosteroids (P=0.001) and less biotherapy (P<0.010) at diagnosis. Relapses (P<0.05) and death (8.6% vs 4.9%) were more frequent in children TAK than in adults. CONCLUSION: Paediatric TAK seems more severe than adult TAK. Therefore, paediatrics patients may require closer monitoring and systemic use of biological treatment.