Background/Purpose: This study was conducted to evaluate the extent to which disease modifying antirheumatic medications (DMARDs) used as part of triple therapy for treatment of rheumatoid arthritis (RA) including methotrexate, sulfasalazine and hydroxychloroquine are associated with incident fractures in postmenopausal women with RA.

Methods: Of the 161,808 postmenopausal women who were enrolled in the Women’s Health Initiative (WHI), all who self-reported at baseline a history of RA and had either a DMARD and/or a biologic use or presence of anti-cyclic citrullinated peptide (Anti-CCP) antibody were included as RA patients. There were too few users of standard triple therapy (methotrexate, sulfasalazine and hydroxychloroquine use (n=9)) to determine the association of standard triple therapy use with incident fractures. Therefore, incident fractures in postmenopausal women with RA following use of methotrexate, sulfasalazine and/or hydroxychloroquine alone or as “combination therapy” (methotrexate and sulfasalazine or methotrexate and hydroxychloroquine) were estimated by Cox proportional hazards models using hazard ratios (HR) and 95% confidence intervals (CI) after consideration of potential confounders.

Results: There were 1,201 postmenopausal women with RA enrolled in WHI included in these analyses, of which 74% were Caucasian, 17% were African American and 9% were of other or unknown race/ethnicity. Of the postmenopausal women with RA, 421 (35%) had not used either methotrexate, sulfasalazine or hydroxychloroquine while 519 (43%) had used methotrexate, 83 (7%) sulfasalazine and 363 (30%) hydroxychloroquine at some time during study follow-up. Over a median length of 6.46 years of follow-up, in multivariable adjusted models, no statistically significant association was found between methotrexate (HR 1.1 [95% CI 0.8-1.6]), sulfasalazine (HR 0.6 [95% CI 0.2-1.5]) or hydroxychloroquine use (HR 1.0 [95% CI 0.7-1.5]) and incident fractures or between combination therapy with methotrexate and sulfasalazine or methotrexate and hydroxychloroquine use (HR 0.9 [95% CI 0.5-1.6]) and incident fractures.

Conclusion:

In conclusion, use of methotrexate, sulfasalazine or hydroxychloroquine alone or in combination is not associated with incident fractures in postmenopausal women with RA. Postmenopausal women with RA receiving any component of triple therapy should not be expected to have any substantial reduction in fracture risk from use of these medications.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-association-of-methotrexate-sulfasalazine-and-hydroxychloroquine-use-with-incident-fractures-in-postmenopausal-women-with-rheumatoid-arthritis-findings-from-the-womens-health-initiative/