Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Adverse Events and Factors Associated with Toxicity in Patients with Early Rheumatoid Arthritis Treated with Methotrexate (the CAMERA study)
Verstappen1, S.M.M., Bakker2, M.F., Heurkens2, A.H.M., van der Veen2, M.J., Kruize2, A.A., Geurts2, M., Jacobs2, J.W.G.
In the CAMERA study (Computer Assisted Management in Early Rheumatoid Arthritis) we found that more patients with rheumatoid arthritis (RA) in the intensive methotrexate (MTX) strategy group compared to the conventional MTX strategy group achieved at least one period of remission. However, to compare the value of the two strategies, both beneficial effects and adverse events (AE) are important to weigh. Therefore, the objective of this study was to evaluate toxicity profiles in patients with early RA treated either according to an intensive or a conventional treatment strategy approach with MTX and to study factors associated with MTX related toxicity.
Data were used from the CAMERA study in which AEs were recorded at each visit using a predefined form. Data on AEs were compared between the intensive strategy group (n=149) and conventional strategy group (n=140). Logistic regression analyses were used to identify possible associations between factors assessed at baseline, including demographic variables, clinical factors and laboratory values, and withdrawal due to MTX related AEs (adjusted for treatment group and NSAID use at baseline) in the total study population and for liver toxicity at follow-up (adjusted for NSAID use at baseline) for the two strategy groups separately. We present Odds ratios (OR) with 95% confidence intervals (95%CI).
Although significantly more patients in the intensive strategy group (95%) experienced MTX related AEs compared to the conventional strategy group (90%), all recorded AEs were relatively mild and often reversible. The percentages of patients with an event were respectively: GI symptoms (66% vs 54%, p=0.030); mucocutaneous (54% vs 40%, p=0.025); CNS (59% vs 39%, p=0.001); hepatic (55% vs 35%, p=0.001); renal (39% vs 44%, p=0.403); haematological (26% vs 11%, p=0.001); and general AE (27% vs 15%, p=0.015). None of the baseline variables was associated with withdrawal due to MTX related AEs in the univariate regression analyses, but a higher BMI was significantly associated with withdrawal due to MTX related adverse events in the multiple regression analyses (OR 1.21, 95%CI 1.02 to 1.44). There was a trend towards an association between diminished creatinine clearance and MTX withdrawal (OR 0.97, 95%CI 0.94 to 1.00). For liver toxicity, increased serum transaminase and creatinine levels at baseline were associated with liver toxicity during follow-up.
Although the occurrence of AEs was higher in the intensive strategy group than in the conventional strategy group, the previously observed clinical efficacy of an intensive treatment strategy seems to outweigh the observed toxicity profiles. When starting MTX, attention should be given to patients with a high BMI and those with increased transaminase levels and decreased renal function.
To cite this abstract, please use the following information:
Verstappen, S.M.M., Bakker, M.F., Heurkens, A.H.M., van der Veen, M.J., Kruize, A.A., Geurts, M., et al; Adverse Events and Factors Associated with Toxicity in Patients with Early Rheumatoid Arthritis Treated with Methotrexate (the CAMERA study) [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1617