Table 1 Predicting inefficacy at 1 and 2 years Predictor Number of patients N (%) Female gender N (%) Age diagnosis (years) Age MTX onset (years) Symptom duration—prior MTX (months) RF positive (yes/no) ARA criteria (yes/no) SJC TJC 28 SJC 28 TJC Baseline CRP* Baseline DAS28* Baseline HAQ SE positive (yes/no){ N (%) Steroids (yes/no) 1 year Inefficacy 25 (8) 18 (72) 60.6 (53.3–73.1) 61.2 (53.9–73.2) 6.01 (3.35–8.01) 14 (56) 11 (44) 7 (2–10) 4 (1–12) 4 (1–9) 3 (0–7) 20 (6–36) 3.7 (2.8–4.7) 1 (0.375–2) 21 (91) 6 (24) Still on 231 (75) 147 (64) 59.3 (48.3–69) 60 (50.8–69.8) 6.27 (3.75–12.68) 94 (41) 121 (52) 4 (1–11) 5 (1–15) 4 (1–9) 3 (0–10) 13 (5–26) 3.9 (3.0–4.8) 1 (0.5–1.625) 126 (64) 39 (17) p Value 0.8 0.34 0.38 0.38 0.12 0.43 0.8 0.94 0.84 0.28 0.33 0.59 0.57 0.009 0.38 2 years Inefficacy 49 (16) 33 (67) 60.6 (52.5–68.6) 61.2 (53.1–68.7) 6.01 (3.35–7.95) 25 (51) 25 (51) 5 (2–12) 4 (0–17) 4 (1–10) 3 (0–7) 20 (6–38) 3.7 (2.8–4.8) 1.125 (0.5–1.875) 37 (84) 19 (38) Extended report Still on 188 (61) 117 (62) 58.7 (46.9–69.5) 59.4 (49.1–70.5) 6.09 (3.56–14.59) 87 (46) 101 (54) 5 (1–11) 5 (1–13) 4 (1–9) 4 (0–10) 13 (5–26) 4.0 (3.0–4.8) 1 (0.5–1.625) 99 (63) 18 (10) p Value 0.5 0.43 0.55 0.11 0.25 0.74 0.72 0.77 0.64 0.26 0.26 0.67 0.34 0.01 0.001 ARA, American Rheumatism Association; CRP, C-reactive protein; DAS, disease activity score (using 28 joint counts); HAQ, Health Assessment Questionnaire; MTX, methotrexate; RF, rheumatoid factor; SE, shared epitope; SJC, swollen joint count; TJC, tender joint count. This table illustrates clinical variables in those stopping for inefficacy and those remaining on treatment at 1 and 2 years. Results expressed as median (IQR) unless stated. *293 patients had baseline CRP available and, therefore, could have DAS28 results calculated. {260 patients had DNA samples and were successfully genotyped for SE. significantly improve the predictive power of the model, AUC ROC 0.7 (95% CI 0.6 to 0.81). The results were similar at 2 years unadjusted AUC ROC 0.6 (95% CI 0.54 to 0.67) and adjusted for the same variables AUC ROC 0.74 (95% CI 0.65 to 0.81). Predicting adverse events Thirty-four patients stopped MTX for adverse events in the first year, this increased to 46 patients by 2 years. Baseline clinical and demographics of the adverse event group compared with those remaining on treatment are shown in table 3. At 1 year, patients stopping MTX for adverse events had a higher baseline median HAQ score (1.625 vs 1, p = 0.02), higher TJC (9 vs 5, p = 0.05) but lower CRP (8 vs 13, p = 0.04) than those remaining on treatment. There was also a trend for female patients to be more likely to stop MTX for adverse events (79% vs 64%, p = 0.07), although this did not reach statistical significance. By 2 years, only lower CRP (7 vs 13, p = 0.01) was associated with stopping MTX for adverse events, although a trend towards a higher TJC in those stopping for adverse events remained. No association was observed between SE status and adverse events on MTX. Using logistic regression, higher baseline HAQ score was associated with stopping MTX for adverse events at 1 year (unadjusted OR 1.84 95% CI 1.12 to 3.01, p = 0.02). Adjusting for age, gender, symptom duration and steroid use did not affect this association (table 4). Despite this association, however, HAQ was only moderate in predicting adverse events on MTX, AUC ROC unadjusted 0.63 (95% CI 0.52 to 0.73) and 0.68 (95% CI 0.58 to 0.78) when adjusted for age, gender, symptom duration and steroid use. Adding in the other factors significant on univariate analysis (TJC and CRP) did not further improve the predictive power of the model AUC ROC 0.69 (95% CI 0.6 to 0.79). At 2 years, the results were similar, with a trend for higher HAQ to be associated with stopping MTX for adverse events. This no longer reached statistical significance (table 4). Predicting methotrexate failure overall Fifty-nine patients failed MTX monotherapy at 1 year, this increased to 95 patients by 2 years. Baseline clinical and demographics of the failure group compared with those remaining on MTX monotherapy are shown in table 5. At 1 year, patients failing MTX monotherapy had a higher baseline median HAQ score (1.5 vs 1, p = 0.04) and were more likely to be SE positive (78% vs 64%, p = 0.05) than those remaining on monotherapy, although neither of these associations remained statistically significant at 2 years. Again these factors were poor at predicting MTX failure, AUC ROC HAQ unadjusted 0.59 (95% CI 0.5 to 0.68) and 0.63 (95% CI 0.55 to 0.72) when adjusted for age, gender, symptom duration and steroid use (table 6). DISCUSSION This cohort provides an insight into the ‘‘real world’’ response to MTX within an unselected inception cohort of patients with IP starting MTX as their first DMARD. Although the total numbers starting MTX as their first DMARD (with clinical data Table 2 Predicting inefficacy Predictor SE positive 1 year Unadjusted OR (95% CI) 5.83 (1.33 to 25.61) Adjusted OR p Value (95% CI) 0.02 5.88 (1.32 to 26.25) p Value 0.02 2 years Unadjusted OR (95% CI) 3.04 (1.27 to 7.27) Adjusted OR p Value (95% CI) 0.01 3.04 (1.21 to 7.62) p Value 0.02 MTX, methotrexate; SE, shared epitope. This table illustrates the odds of stopping MTX for inefficacy—OR (95% CI) displayed as unadjusted and adjusted for age, gender, symptom duration and steroid use at baseline. Ann Rheum Dis 2009;68:57–62. doi:10.1136/ard.2008.088237 59