OBJECTIVES: We aimed to evaluate the effect of anti-rheumatic drugs including methotrexate, hydroxychloroquine, sulfasalazine, leflunomide and glucocorticoids on diabetic foot disease (DFD) among patients diagnosed with both type 2 diabetes mellitus (T2DM) and rheumatoid arthritis (RA).

METHODS: This was a population-based retrospective cohort study, using time-dependent exposure design, of individuals diagnosed with T2DM and RA using data from the Clinical Practice Research Datalink database. Five mutually exclusive groups were determined: 1) methotrexate with or without any other conventional disease-modifying anti-rheumatic drugs (cDMARDs) other than hydroxychloroquine (not prescribed hydroxychloroquine); 2) hydroxychloroquine with or without any other cDMARDs other than methotrexate (not prescribed methotrexate); 3) methotrexate and hydroxychloroquine with or without other cDMARDs; 4) other cDMARDs (sulfasalazine and/or leflunomide with or without glucocorticoids) without a prescription for methotrexate and/or hydroxychloroquine; 5) no cDMARDs use (periods of no cDMARD prescription after previous initiation of cDMARDs when considering as a time-dependent exposure). The outcomes included incident composite DFD, peripheral neuropathy and foot ulcer.

RESULTS: There was no significant difference in the hazard of composite DFD between individuals prescribed methotrexate, hydroxychloroquine, methotrexate + hydroxychloroquine or non-use of cDMARDs compared to other cDMARDs (methotrexate: aHR 1.09, 95% CI, 0.96-1.26; hydroxychloroquine: aHR 0.98, 95% CI 0.80, 1.22; methotrexate + hydroxychloroquine: aHR 1.04, 95% CI 0.84, 1.29; non-user: aHR 0.94, 95% CI 0.83, 1.08). There was no evidence of association between the use of methotrexate hydroxychloroquine, or methotrexate + hydroxychloroquine and peripheral neuropathy or foot ulcer. Glucocorticoids was not observed to be associated with the hazard of DFD (aHR 1.03, 95%CI 0.94, 1.14).

CONCLUSIONS: The use of cDMARDs including methotrexate, hydroxychloroquine or the combination use of the two did not largely show beneficial or harmful effects on developing DFD compared to using sulfasalazine and/or leflunomide. cDMARDS are safe to use in patients with RA with comorbid T2DM.