Best of 2022: Methotrexate Side Effects Save

Editor's note: this article originally published on February 7, 2022, and is being shared again as a Best of 2022. Enjoy!

Data came from the UK Rheumatoid Arthritis Medication Study (RAMS), a prospective cohort of early RA patients starting methotrexate (MTX) shows that in the first year, adverse events (AE) were common, but not serious.

A total of 1069 patients were enrolled and followed at 6 and 12 month intervals.  Adverse events were noted:

• 77.5% experienced at least one AE.
• Gastrointestinal AEs 42%
• Neurological 28.6%
• Mucocutaneous 26%)
• Pulmonary 20.9%
• Elevated alanine transaminase 18%
• Hematologic AEs 5.6%.

Risk factors associated with AEs were:

• women vs men (gastrointestinal, mucocutaneous, neurological)
• alcohol consumption (nausea, alopecia, mucocutaneous)
• Hematologic AES were less in those who were older , higher estimated Glomerular Filtration Rate (eGFR), and alcohol consumption 

In the same issue of Rheumatology, another cohort analysis compared side effect rates in RA patients treated with either MTX or leflunomide (LEF) in autoimmune rheumatic diseases (AIRD) treated with low-dose MTX or LEF. Data drawn from the UK Clinical Practice Research Datalink included 15, 670 MTX and 2,689 LEF treated cohorts.

Drug discontinuation rates in the 1st year for an abnormal blood-test was

• MTX: 6.16/1000 person-years; cumulative MTX discontinuations was 1 in 24 at 1 year; 
• LEF: 9.42/1000 person-years; cumulative discontinuation w/ LEF was 1 in 9 at 1 year
• Whiel MTX and LEF dose reductions were comparable in year 1, however, thereafter MTX dose was reduced more often than LEF [16.60 vs 8.10 /1000 person-years].

Overall MTX discontinuations were uncommon and fewer than LEF were discontinued .