METOTrEXaTO EM EVIDÊNCIA
2ª Edição | Setembro 2023
Follow UP MTX
Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated
Results: A total of 999 patients (mean age 60.8 ± 12 years, 62.3% females) were included. Of 976 with valid TE values, 149 (15.3%) had liver stiffness >−7.9 kPa. Of 892 with a valid ELF, 262 (29.4%) had ELF >−9.8. Age and BMI were independently associated with elevated liver stiffness and ELF. Neither MTX cumulative dose nor duration was associated with elevated liver stiffness. Diabetes was the most sig- nificant risk factor associated with liver stiffness >−7.9 kPa (adjusted odds ratio = 3.19; 95% CI 1.95–5.20; p −9.8 (odds ratio = 1.76; 95% CI 1.20–2.56; p = 0.003), suggesting the degree of joint inflammation in RA may confound ELF as a non-invasive marker of liver fibrosis.
Conclusion: The risk of liver fibrosis attributed to MTX itself might have been previously overestimated; there is a need to consider modifying current monitoring guidelines for MTX.
https://pubmed.ncbi.nlm.nih.gov/32475009/
Osteoporos Int. 2021 May;32(5):805-816.doi: 10.1007/s00198-020-05743-z. Epub 2020 Nov 18.
Speak UP MTX
British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: immunomodulatory anti-rheumatic drugs and corticosteroids
Recommendations for methotrexate in pregnancy and breastmilk exposure:
i) MTX at any dose should be avoided in pregnancy and stopped at least one month in advance of planned conception, when it should be switched to another pregnancy-compatible drug to ensure maintenance of maternal disease suppression (GRADE 1A, SOA 98%).
ii) In women treated with low-dose (25 mg/week) MTX within one month prior to conception, folic acid supplementation (5 mg/day) should be continued up to 12 weeks of pregnancy (GRADE 1B, SOA 99.5%).
iii) In unintended pregnancy on low-dose (25 mg/week) MTX, there is minimal risk to the foetus; the drug should be stopped immediately, folic acid supplementation (5 mg/day) continued, and a careful evalua- tion of foetal risk with early referral to a foetal medicine department considered (GRADE 1C, SOA 100%).
https://pubmed.ncbi.nlm.nih.gov/36318966/
Russell MD, et al.; BSR Standards, Audit and Guidelines Working Group. British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: immunomodulatory anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford). 2023 Apr 3;62(4):e48-e88. doi: 10.1093/rheumatology/keac551. Erratum in: Rheumatology (Oxford). 2022 Dec 13;: PMID: 36318966; PMCID: PMC10070073.
Methotrexate therapy associated with a reduced rate of new-onset uveitis in patients with biological-naïve juvenile idiopathic arthritis
Recommendations: Ninety-two patients with JIA were included and characteristics were similar between cases with JIA-U (n=46) and controls (n=46). Both ever-use of MTX and exposure years were lower in cases with JIA-U than in controls. Cases with JIA-U significantly more often discontin- ued MTX treatment (p=0.03) and out of those who did, 50% afterwards developed uveitis within 1 year. On adjusted analysis, MTX was asso- ciated with a significantly reduced new-onset uveitis rate (HR: 0.35; 95% CI: 0.17 to 0.75). No different effect was observed between a low (<10 mg/m2/week) and standard MTX dose (≥10 mg/m2/week).
Conclusion: This study demonstrates an independent protective ef- fect of MTX on new-onset uveitis in patients with biological-naïve JIA. Clinicians might consider early initiation of MTX in patients at high uveitis risk. We advocate more frequent ophthalmologic screening in the first 6-12 months after MTX discontinuation.
van Straalen JW, et al. Methotrexate therapy associated with a reduced rate of new-onset uveitis in patients with biological-naïve juvenile idiopathic arthritis. RMD Open. 2023 Apr;9(2):e003010. doi: 10.1136/rm- dopen-2023-003010. PMID: 37094979; PMCID: PMC10151999.
Open UP MTX
Tofacitinib versus methotrexate as the first- line disease-modifying antirheumatic drugs in the treatment of rheumatoid arthritis: An open-label randomized controlled trial
Results: LDA in DAS28-CRP was achieved in 17 (34.7%) tofacitinib pa- tients and 18 (35.3%) MTX patients (p=.95). Fourteen (28.6%) and 11 (21.6%) tofacitinib and MTX patients, respectively, achieved LDA by DAS28-ESR (p=.42). Tofacitinib and MTX groups achieved LDA similar- ly in CDAI (36.7% against 37.3%; p=.96) and SDAI (38.8% vs. 39.2%; p=.96). There was no significant difference in achieving remission be- tween the groups. At 12 weeks, tofacitinib reduced ESR and CRP (p < .05). Composite measures and functional status decreased within groups but not between groups (p > .05). Five (13.51%) tofacitinib patients developed hypertension. MTX caused gastrointestinal problems in 12 (30%) individ- uals. Two MTX (5%) and two tofacitinib (5.4%) patients had increased liver enzymes and renal impairment, respectively. Tofacitinib had 5.4% infection compared with 5% for MTX.
Conclusion: As tofacitinib may be more effective than MTX according to previous reports such as the ORAL Start study, high-dose MTX (25 mg/ week, subcutaneously) used in this study may be as efficacious as tofacitinib in patients with established RA who were DMARD naive or had not received a therapeutic dose of DMARDs. However, adverse effects differed between groups.
https://onlinelibrary.wiley.com/doi/10.1111/1756-185X.14801
Atallah E et al. Risk of liver fibrosis associated whith long-term methotrexate therapy may be overestimated. J Hepatol.2023 May; 78(5):989-997. doi: 10.1016/j.jhep.2022.12.034. Epub 2023 Jan 23. PMID: 36702175
