IL-6R Blockade with Sarilumab Plus Methotrexate Results in Changes in Clinical and Laboratory Parameters Associated with Chronic Inflammation in Patients with Moderate-to-Severe RA in a Phase 3 Study

Maxime Dougados¹, Ernest H. Choy², Hideto Kameda³, Janet van Adelsberg⁴, Jonathan Fay⁵, Stefano Fiore⁶, Chunpeng Fan⁷ and Georg Schett⁸, ¹Paris-Descartes University, Paris, France, ²Cardiff University, Institute of Infection and Immunity, Tenovus Building, University Hospital of Wales, Cardiff, United Kingdom, ³Dep of Rheumatol/Clin Immun, Saitama Medical Ctr, Kawagoe, Japan, ⁴Clinical Science, Regeneron Pharmaceutials, Inc., Tarrytown, NY, ⁵Regeneron Pharmaceuticals, Inc., Tarrytown, NY, ⁶Sanofi, Bridgewater, NJ, ⁷Biostatistics, Sanofi, Bridgewater, NJ, ⁸Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Rheumatoid arthritis (RA)

Session Information

Date: Tuesday, November 10, 2015

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster III

Session Type: ACR Poster Session C

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

Background/Purpose: Chronic inflammation in RA
is characterized by biochemical changes, including decreased hemoglobin, elevated
CRP, changes in lipid metabolism, and hypoalbuminemia.¹Some
parameters, including CRP, are associated with RA disease activity, rapid structural
disease progression, and comorbidities (eg, cardiovascular disease).^2,3
Chronic inflammation in RA is also associated with non-focal complaints⁴;
some, like weight loss, are not measured by response-to-treatment measures
routinely used in clinical studies. In the phase 3 MOBILITY study
(NCT01061736), investigational agent sarilumab (150 or 200 mg every 2 wks [q2w])
+ MTX demonstrated efficacy vs placebo (Pbo) in adults with active, moderate-to-severe
RA with inadequate response to MTX.⁵ The most common treatment-emergent
adverse events with sarilumab included infections, neutropenia, injection site
reactions, and increased transaminases. Laboratory abnormalities were
consistent with IL-6 blockade. In the present analysis of MOBILITY, effect of
sarilumab on laboratory parameters associated with chronic inflammation was
assessed.

Methods: Changes in laboratory parameters from
baseline through 52 wks with Pbo (n=427), sarilumab 150 mg q2w (n=431), and
sarilumab 200 mg q2w (n=424) were assessed.

Results: Laboratory parameters remained
relatively unchanged in the Pbo group through wk 52 (Table). Decreases in serum
amyloid A, fibrinogen, and CRP were observed in the sarilumab group beginning
at wk 2 and remained below baseline through wk 52. Increases in hemoglobin and
albumin were also observed. An increase in total cholesterol levels was observed
starting at ~4 wks in all 3 groups (mean increase of ~20 mg/dL for both sarilumab
groups) and remained at these levels through wk 52. Low-density lipoprotein (LDL)
cholesterol increased from <160 to ≥160 mg/dL in more patients treated
with sarilumab (27.8% in 200 mg, 21.1% in 150 mg vs 11.5% in Pbo). Slight
weight gain was observed with either dose of sarilumab (1.32 and 1.85 vs Pbo, 0.07
kg), with more patients treated with sarilumab 150 or 200 mg (32.7% and 34.2%,
respectively) experiencing a ≥5% increase from baseline (vs 15.0% with
Pbo).

Conclusion: Inhibition of IL-6 signaling via
sarilumab was associated with changes in parameters associated with chronic
inflammation including a decrease in CRP, an increase in hemoglobin,
normalization of albumin and fibrinogen, and an increase in total and LDL cholesterol.
Increase in weight was also observed in both sarilumab groups across the 52-wk
study.

1. Yoshida et al. BioMed Res Int. 2014;2014:698313.

2. Scott. J Rheumatol. 2004;69;55-65.

3. Yeh. Circulation. 2004;109(suppl II):II11-II14.

4. Suresh. J R Soc Med. 2004;97:421-424.

5. Genovese et al. Arthritis Rheumatol. 2015;67:1424-1437.

Table. Change From Baseline to Week 52 in Laboratory Parameters Associated With Chronic Inflammation Following Treatment With Sarilumab in MOBILITY
Laboratory assessment, mean (SD)	Placebo + MTX (n=427)	Sarilumab 150 mg q2w + MTX (n=431)	Sarilumab 200 mg q2w + MTX (n=424)
Hemoglobin, g/L	-0.58 (10.40)	9.15 (10.96)	9.81 (11.06)
Serum amyloid A protein, mg/L	3.01 (69.47)	-58.87 (89.61)	-63.36 (85.80)
Fibrinogen, g/L	-0.15 (1.37)	-2.14 (1.60)	-2.24 (1.54)
Albumin, g/L	0.67 (2.81)	4.23 (3.86)	4.71 (3.57)
Total cholesterol, mg/dL	0.52 (27.60)	20.73 (31.56)	22.96 (32.08)
CRP, mg/L	1.01 (23.33)	-16.91 (26.70)	-18.42 (21.93)
CRP, C-reactive protein; MTX, methotrexate; q2w, every 2 weeks; SD, standard deviation.

Disclosure: M. Dougados, SANOFI,PFIZER,NOVARTIS,ABBVIE,UCB,ROCHE,BMS,MERCK, 2,SANOFI,PFIZER,NOVARTIS,ABBVIE,UCB,ROCHE,BMS,MERCK, 5,SANOFI,PFIZER,NOVARTIS,ABBVIE,UCB,ROCHE,BMS,MERCK, 8; E. H. Choy, Abbott Laboratories, Amgen, Boehringer Ingelheim, Chelsea Therapeutics, Chugai Pharma, Ferring Pharmaceuticals, GSK, Jazz Pharmaceuticals, Jenssen, MSD, Novartis, Pierre Fabre Medicament, Pfizer, Novimmune, Roche, and UCB, 2,Abbott Laboratories, Allergan, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Chelsea Therapeutics, Chugai Pharma, Daiichi Sankyo, Eli Lilly, Ferring Pharmacuetical, GSK, Hospita, ISIS, Jazz Pharmaceuticals, Jensen, MedImmune, Merrimack Pharmaceutical, MS, 5,Abbott Laboratories, Amgen, Boehringer Ingelheim, Chugai Pharma, Eli Lilly, Jazz Pharmaceuticals, MSD, Novartis, Pfizer, Pierre Fabre Medicament, Regeneron, Roche, Schering Plough, Sanofi-Aventis, Synovate and UCB, 8; H. Kameda, None; J. van Adelsberg, Regeneron, 1,Regeneron, 3; J. Fay, Regeneron, 1,Regeneron, 3; S. Fiore, Sanofi-Aventis Pharmaceutical, 1,Sanofi-Aventis Pharmaceutical, 3; C. Fan, Sanofi, 1,Sanofi, 3; G. Schett, None.

To cite this abstract in AMA style:

Dougados M, Choy EH, Kameda H, van Adelsberg J, Fay J, Fiore S, Fan C, Schett G. IL-6R Blockade with Sarilumab Plus Methotrexate Results in Changes in Clinical and Laboratory Parameters Associated with Chronic Inflammation in Patients with Moderate-to-Severe RA in a Phase 3 Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/il-6r-blockade-with-sarilumab-plus-methotrexate-results-in-changes-in-clinical-and-laboratory-parameters-associated-with-chronic-inflammation-in-patients-with-moderate-to-severe-ra-in-a-phase-3-study/. Accessed .

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