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Adherence to disease‐modifying antirheumatic drugs and the effects of exposure misclassification on the risk of hospital admission
Author(s) -
Grijalva Carlos G.,
Kaltenbach Lisa,
Arbogast Patrick G.,
Mitchel Edward F.,
Griffin Marie R.
Publication year - 2010
Publication title -
arthritis care and research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.032
H-Index - 163
eISSN - 2151-4658
pISSN - 2151-464X
DOI - 10.1002/acr.20087
Subject(s) - medicine , leflunomide , methotrexate , rheumatoid arthritis , hazard ratio , regimen , etanercept , confidence interval , prednisone
Objective To describe the effect of different exposure classification strategies for disease‐modifying antirheumatic drugs (DMARDs) on drug‐outcome associations. Methods We studied the association between DMARD initiation and all‐cause hospitalizations in patients with rheumatoid arthritis (RA), 1995–2005. Initiators of DMARDs and oral glucocorticoids were followed for ≤180 days. We compared 2 strategies for exposure classification: a persistent exposure required (PER) approach, in which followup stopped when the regimen changed; and a persistent exposure ignored (PEI) approach, in which followup continued despite regimen changes. For PEI, adherence was assessed using the medication possession ratio. All‐cause hospitalization risk was compared among RA regimen initiators using Cox models and methotrexate as the reference. Results We identified 28,906 episodes of medication initiation. In PER analyses, tumor necrosis factor α antagonists did not increase hospitalization risk compared with methotrexate, whereas leflunomide did (hazard ratio [HR] 1.36, 95% confidence interval [95% CI] 1.1–1.67). Glucocorticoids increased hospitalization risk (HR 1.29, 1.54, and 2.03 for low, medium, and high doses, respectively). PEI results were similar to PER except that infliximab initiation increased the risk of hospitalization compared with methotrexate (HR 1.46, 95% CI 1.19–1.8), and most other effects were closer to the null. In PEI, adherence ranged from 73% for etanercept to 6% for glucocorticoids and adherence to methotrexate was 59%. Conclusion Compared with methotrexate initiation, leflunomide or glucocorticoid initiation consistently increased all‐cause hospitalizations in the first 180 days of use. Most PER and PEI estimates were similar; observed differences in risk between these methods were likely due to differences in adherence.