Background While rheumatoid arthritis (RA) has been associated with the increased risk of developing type 2 diabetes mellitus (T2DM), few basic science studies have indicated the possible beneficial role of some biologic disease-modifying antirheumatic drugs (bDMARDs), including the interleukin-6 (IL-6) based DMARDs, on insulin resistance in patients with RA.
Objectives To evaluate the impact of treatment with bDMARDs, including the IL-6 inhibitors, on the probability of developing T2DM in a real world setting.
Methods From the Centricity Electronic Medical Records of GE Healthcare, a longitudinal cohort of 192,509 US adults (age≥18 years) with diagnosis of RA from January 2000 to April 2016 was selected. Patients were excluded if they had a prior history of diabetes, cancer and micro- or macro-vascular diseases at diagnosis of RA. Four mutually exclusive antirheumatic treatment groups (TGs) were identified by diagnosis date (Dx) and treatment initiation date (ID): tocilizumab (TCZ, n=843), TCZ+Other bDMARDs (TCZ+obDMARD, n=2489), non-TCZ other bDMARDs (obDMARD, n=45,262) and no bDMARD (n=143,915). Within the treatment groups, 142,225 patients had a minimum 6 months of exposure before development of T2DM or end of follow-up. Treatment-effects regression models were used to estimate the probabilities (95% CI) of developing T2DM during follow-up in the 4 TGs after adjusting and balancing with inverse-probability-weighted regression for various factors including age, sex, smoking status, body mass index, use of non-biologic DMARDs, use of statins, anaemia status and follow-up time post ID.
Results At diagnosis, the 142,225 patients were on average 55 years old, 22% male, 71% white Caucasian, 13% with anaemia, and 32% obese with mean BMI of 29 kg/m2. About 28%/42% were using statins/MTX at diagnosis or during follow-up before development of T2DM. During mean 4.6 years of follow-up from Dx, 2.6%/2.6%/5.3%/5.8% developed T2DM in the TCZ/TCZ+obDMARD/obDMARD/no bDMARD TGs. The adjusted probability of developing T2DM was 0.05 (95% CI: 0.04, 0.05) in no bDMARD group; with significantly lower probability of developing T2DM in TCZ [0.02 (95% CI: 0.01, 0.04)], TCZ+obDMARD [0.03 (95% CI: 0.02, 0.04)] and obDMARD [0.01 (95% CI: 0.01, 0.02)] groups (Table). Hypertension, higher BMI and Statin use were associated with significantly higher probability of developing T2DM by 0.25 (95% CI: 0.16, 0.35), 0.08 (95% CI: 0.07, 0.08) and 0.36 (95% CI: 0.27, 0.47) respectively. Patients with anaemia had 8% higher likelihood of developing T2DM (p=0.13). Among those who received any bDMARD, those who ever received TCZ had significantly lower probability of developing T2DM (0.024, 95% CI: 0.02, 0.03), compared to those who were never exposed to TCZ therapy.
Conclusions This study indicates the possible beneficial role of IL-6 inhibitors (TCZ) in reducing the likelihood of developing T2DM among adults without major co-morbidities at diagnosis of RA.
Acknowledgements Funding by F. Hoffmann-La Roche/Genentech.
Disclosure of Interest S. Paul Grant/research support from: Therapeutic Innovations Australia, O. Montvida: None declared, J. Best Employee of: Genentech, S. Gale Employee of: Genentech, A. Pethoe-Schramm Employee of: F. Hoffmann-La Roche, K. Sarsour Employee of: Genentech