Table 1 Most common adverse events (AEs) attributed to methotrexate (MTX) and permanent discontinuation due to toxicity in patients with rheumatoid arthritis (RA): pooled results from 21 prospective cohorts (level of evidence 2b)4^–24

	Patients	Mean dose of MTX (mg/week)	Mean duration of MTX (months)	Number of all AEs	Permanent discontinuation	Gastro-intestinal	Liver	Skin/hair	Central nervous system	Cytopenia	Lung
Number	3463	8.8	36.5	2524	315/3007*	1065	640	309	191	179	84 (15†)
Range	24–1155	4.6–18	27–132	22–475		10–257	0–122	0–111	0–58	0–27	0–28
%				72.9	10.5	30.8	18.5	8.9	5.5	5.2	2.4 (0.43)†

*Total number of patients in studies with data available concerning permanent discontinuation of MTX.
Gastrointestinal (GI): stomatitis, ulcer, abdominal pain, GI bleed, dyspepsia, nausea, vomiting, diarrhoea, weigh loss, appetite loss; liver toxicity: increase of aspartate aminotransferase and/or alanine aminotransferase upper limit of normal; skin/hair: ulcer, pruritis, skin rash, alopecia, skin itching, moon face, eczema; central nervous system: headache, depression, blurred vision, transient ischemic attack, stroke, vertigo, lethargy, malaise, fatigue; cytopenia: haemoglobin decreased >2 gm/dl or platelets <150 000/mm³, white blood cells <3500/mm³; lung: MTX pneumonitis (†), pulmonary dysfunction, cough and unspecified pulmonary adverse drug reactions.