ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1822

The Effect of Sarilumab in Combination with Dmards on Fasting Glucose and Glycosylated Hemoglobin in Patients with Rheumatoid Arthritis with and without Diabetes

Mark C. Genovese1, Roy Fleischmann2, Owen Hagino3, Chih-Chi Hu4, Claudia Pena-Rossi3, Jonathan Sadeh3, Neil M.H. Graham5, Erin K. Mangan5, Hubert van Hoogstraten4 and Thomas Mandrup-Poulsen6, 1Stanford University Medical Center, Palo Alto, CA, 2Metroplex Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, 3Sanofi, Bridgewater, NJ, 4Sanofi Genzyme, Bridgewater, NJ, 5Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 6University of Copenhagen, Copenhagen, Denmark

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: ,

Session Information

Date: Monday, November 6, 2017

Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy I: Outcomes Therapy

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: IL-6 involvement has been reported in glucose metabolism.1-4 Sarilumab, a human mAb blocking the IL-6Rɑ, was evaluated for treatment of RA in 3 clinical trials: MOBILITY, TARGET, and MONARCH. This analysis examined effects of sarilumab or placebo (Pbo), plus DMARDs, on fasting glucose and glycosylated hemoglobin (HbA1c) in patients with RA, with and without diabetes.

Methods: Fasting glucose and HbA1c data were collected during 2 Pbo-controlled studies of sarilumab + DMARDs: MOBILITY and TARGET. Studies excluded patients with HbA1c ≥9.0%. Patients with baseline (BL) and ≥1 post-BL sample were included in post hoc pooled analyses and categorized as diabetic (DIAB) or non-DIAB based on medical history of diabetes or prior use of antidiabetic medication. Changes from BL in fasting glucose, HbA1c, and weight were analyzed with a linear regression model. Spearman rank correlation coefficient was calculated for changes in glucose, HbA1c, and high-sensitivity (hs)-CRP. Changes in these parameters were stratified by clinical response. Clinical meaningfulness was based on comparison with results of clinical trials with antidiabetic medications.5

Results: The DIAB group (n=179) compared with the non-DIAB group (n=1803) had higher BL body weight (mean ± SD, kg: 84.8 ± 21.4 vs 74.6 ± 18.8) and a larger proportion of patients with BMI ≥30 kg/m2 (56.7% vs 31.9%). Mean fasting glucose and HbA1c at BL were similar across treatment groups (Pbo, and sarilumab 150 and 200 mg every 2 wks [q2w]) but higher in the DIAB group than in the non-DIAB group (Table). Patients in the DIAB group had a greater reduction in fasting glucose at wk 24 compared with those in the non-DIAB group. Decreases in HbA1c occurred in non-DIAB and DIAB sarilumab-treated groups but not with Pbo. The treatment effect was largest in the DIAB group. At wk 24, the change in HbA1c was -0.43% in the DIAB (sarilumab 200 mg q2w) group and +0.17% in the DIAB (Pbo) group (-0.69% mean difference; P<0.001). Reductions in fasting glucose and HbA1c were observed in sarilumab-treated DIAB subgroups independently of changes in hs-CRP, ACR50, or DAS28-CRP remission status, and despite increases in mean body weight. The overall safety of sarilumab did not differ between DIAB and non-DIAB patients with RA.  

Conclusion: Sarilumab + DMARDs reduced fasting glucose and HbA1c in DIAB and HbA1c in non-DIAB patients with RA, independent of changes in body weight, hs-CRP, ACR50, or DAS28-CRP remission status at wk 24. In DIAB patients, the difference in HbA1c reduction between sarilumab 200 mg q2w and Pbo was clinically meaningful.

References:

1. Kristiansen et al. Diabetes. 2005;54(suppl 2):S114-S124.

2. Ellingsgaard et al. Nat Med. 2011;17:1481-1489.

3. Ogata et al. Ann Rheum Dis. 2011;70:1164-1165.

4. Schultz et al. PLoS One. 2010;5:e14328.

5. Bolen et al. Diabetes Medications for Adults With Type 2 Diabetes: An Update. Comparative Effectiveness Review No. 173. 2016.


Disclosure: M. C. Genovese, Roche, Sanofi, GlaxoSmithKline, R-Pharm, and Bird Rock Bio, 2,Roche, Sanofi, GlaxoSmithKline, R-Pharm, and Bird Rock Bio, 5; R. Fleischmann, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, EMD Serono, Genentech, GlaxoSmithKline, Janssen, Eli Lilly, Pfizer, Roche, Sanofi, and UCB, 2,AbbVie, Akros Pharma, Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen, Eli Lilly, Pfizer, Sanofi, and UCB, 5; O. Hagino, Sanofi, 1,Sanofi, 3; C. C. Hu, Sanofi-Genzyme, 1,Sanofi Genzyme, 3; C. Pena-Rossi, Sanofi, 1,Sanofi, 3; J. Sadeh, Sanofi, 1,Sanofi, 3; N. M. H. Graham, Regeneron Pharmaceuticals, Inc., 1,Regeneron Pharmaceuticals, Inc., 3; E. K. Mangan, Regeneron Pharmaceuticals, Inc., 1,Regeneron Pharmaceuticals, Inc., 3; H. van Hoogstraten, Sanofi Genzyme, 3,Sanofi Genzyme, 1; T. Mandrup-Poulsen, Sanofi, 5.

To cite this abstract in AMA style:

Genovese MC, Fleischmann R, Hagino O, Hu CC, Pena-Rossi C, Sadeh J, Graham NMH, Mangan EK, van Hoogstraten H, Mandrup-Poulsen T. The Effect of Sarilumab in Combination with Dmards on Fasting Glucose and Glycosylated Hemoglobin in Patients with Rheumatoid Arthritis with and without Diabetes [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/the-effect-of-sarilumab-in-combination-with-dmards-on-fasting-glucose-and-glycosylated-hemoglobin-in-patients-with-rheumatoid-arthritis-with-and-without-diabetes/. Accessed .

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