Improvement of HbA1c in Patients with Rheumatoid Arthritis and Diabetes Type 2 during Treatment with Tocilizumab

Christof Specker¹, Annette Alberding², Martin Aringer³, Gerd R. Burmester⁴, Jan-Paul Flacke⁵, Michael Hofmann⁶, Peter Kaestner⁷, Herbert Kellner⁸, Frank Moosig⁹, Maren Sieburg¹⁰, Hans-Peter Tony¹¹ and Gerhard Fliedner¹², ¹Rheumatology and Clinical Immunology, Universitätsklinikum Essen, Essen, Germany, ²Internal Rheumatology, Krankenhaus St. Josef, Wuppertal, Germany, ³Medicine III, University Medical Center and Faculty of Medicine TU Dresden, Dresden, Germany, ⁴Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Berlin, Germany, ⁵Rheumatology, Roche Pharma AG, Grenzach-Wyhlen, Germany, ⁶Rheumatology, Chugai Pharma Europe Ltd., Frankfurt, Germany, ⁷Rheumatology, Ambulantes Rheumazentrum, Erfurt, Germany, ⁸Ambulantes Rheumazentrum, Erfurt, Germany, ⁹Rheumatology Center Schleswig-Holstein Mitte, Neumuenster, Germany, ¹⁰Rheumatologische Gemeinschaftspraxis, Magdeburg, Germany, ¹¹Rheumatology/Immunology, Medizinische Klinik II, Universitätsklinik, Würzburg, Germany, ¹²Rheumatological Practice, Osnabrueck, Germany

Meeting: ACR/ARHP Annual Meeting 2018

Keywords: Clinical research, Diabetes, IL-6, rheumatoid arthritis (RA) and therapy

Session Information

Date: Monday, October 22, 2018

Title: Rheumatoid Arthritis – Treatments Poster II: PROs, Safety and Comorbidity

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

Interleukin 6 (IL-6) and C-reactive protein (CRP) are independent risk factors for type 2 diabetes mellitus [1], and IL-6 plays a role in insulin resistance [2]. Ogata et al. demonstrated a tocilizumab (TCZ) induced a reduction of HbA1c in patients with diabetes and rheumatoid arthritis (RA) [3]. The present analysis of the non-interventional study ICHIBAN (final dataset) investigated whether there is a difference in the effectiveness and safety of TCZ in RA patients with and without diabetes.

Methods:

The ICHIBAN study (NCT 01194401) observed patients with RA during treatment with TCZ iv (max. 2 years) between 2010 and 2017. All 3164 patients who had received at least 1 dose TCZ were included in the analysis (Total). Classification of diabetes mellitus was based on the data provided by the investigators at baseline (BL).

Results:

At BL, 9.9% (N=314) of the patients were diabetic and 89.9% (N=2844) were nondiabetic.

Diabetic patients were markedly older compared to nondiabetic patients (mean age: 63.0 vs 54.7 years), had a higher BMI (mean: 29.6 vs 26.6 kg/m²), a higher disease activity (mean DAS28: 5.5 vs 5.2), a more severe functional impairment at BL (mean HAQ: 1.6 vs 1.3%), and a higher comorbidity rate, particularly regarding coronary heart disease (11.5% vs 3.7%), osteoporosis (25.2% vs 16.3%) and depression (11.5% vs 7.0%).

Both subgroups had a comparable response regarding all investigated variables, despite the differences in BL characteristics. DAS28-ESR improved by 2.2 vs 2.1 points in patients with and without diabetes; HAQ improved by 0.2% in both subgroups. HbA1c was markedly decreased (-0.73%) after 104 weeks of TCZ treatment in diabetic patients, whereas there was no change in nondiabetic patients (Tab. 1).

The rates of serious adverse events (20.7% vs 14.3%) and of serious infections (5.4% vs 3.4%) were higher in patients with diabetes than in those without; there was no difference regarding non-serious adverse events.

Conclusion:

The proportion of diabetic patients was slightly higher in the ICHIBAN study (9.9%) compared to the general population (~8%) [4]. An effective clinical response was observed during TCZ iv therapy. Despite a higher disease activity and comorbidity rate at BL, patients with diabetes benefitted to the same extend as nondiabetic patients with regard to all investigated efficacy variables. The safety data underscore the higher risk for infection in diabetic patients. HbA1c decreased from 7.46% to 6.73% in diabetic patients. Further research is necessary to clarify the underlying mechanisms.

References

[1] Pradhan AD, Manson JE, Rifai N, et al. JAMA 2001;286:327–34.

[2] Fève B, Bastard JP. Nat Rev Endocrinol 2009;5:305–11.

[3] Ogata A, Morishima A, Hirano T, et al. Ann Rheum Dis 2011;70:1164–65.

[4] Deutscher Gesundheitsbericht Diabetes 2017; Strahl et al. Z Rheumatol. 2017. doi: 10.1007/s00393-017-0381-6

Disclosure: C. Specker, AbbVie DE GmbH & Co. KG, Bund Deutscher Internisten, CHUGAI PHARMA MARKETING,LTD, Celgene GmbH, Deutsche Gesellschaft f. Innere Medizin, KLINIKVERBUND WUPPERTAL, KOOP. RHEUMAZ.R.-R.EV, KV Westfalen-Lippe, KV Nordrhein, Ludwig Max. Universität München, Luk, 8,AbbVie DE GmbH & Co. KG, Janssen-Cilag, CHUGAI PHARMA MARKETING,LTD, MSD SHARP UND DOHME GMBH, NOVARTIS, UCB PHARMA GMBH, Lilly, BOEHRINGER INGELHEIM, 5,Boehringer, Chugai, DRFZ, GSK, Pfizer, Roche, 2; A. Alberding, None; M. Aringer, Roche, Chugai, 5,Roche, Chugai, 8; G. R. Burmester, Sanofi, Roche, Janssen, 5,Sanofi, Roche, Janssen, 8; J. P. Flacke, Roche Pharma AG, 3; M. Hofmann, Chugai Pharma Europe Ltd., 3; P. Kaestner, Chugai, 5,Novartis, 5; H. Kellner, Roche, 5; F. Moosig, None; M. Sieburg, None; H. P. Tony, Roche Pharma, Abbvie, BMS, Chugai, Janssen, Novartis, Sanofi, Lilly, 5,Roche Pharma, Abbvie, BMS, Chugai, Janssen, Novartis, Sanofi, Lilly, 8; G. Fliedner, None.

To cite this abstract in AMA style:

Specker C, Alberding A, Aringer M, Burmester GR, Flacke JP, Hofmann M, Kaestner P, Kellner H, Moosig F, Sieburg M, Tony HP, Fliedner G. Improvement of HbA1c in Patients with Rheumatoid Arthritis and Diabetes Type 2 during Treatment with Tocilizumab [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/improvement-of-hba1c-in-patients-with-rheumatoid-arthritis-and-diabetes-type-2-during-treatment-with-tocilizumab/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/improvement-of-hba1c-in-patients-with-rheumatoid-arthritis-and-diabetes-type-2-during-treatment-with-tocilizumab/