ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2527

Long-Term Safety with Sarilumab Plus Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) and Sarilumab Monotherapy in Rheumatoid Arthritis (RA): An Integrated Analysis with 9,000 Patient-Years (Pt-Yrs) of Follow-up

Roy Fleischmann1, Yong Lin2, Gregory St. John3, Désirée van der Heijde4, Chunfu Qiu2, Juan José Gómez-Reino5, José A. Maldonado-Cocco6, Marina Stanislav7, Bruno Seriolo8 and Gerd R. Burmester9, 1University of Texas Southwestern Medical Center, Dallas, TX, 2Sanofi Genzyme, Bridgewater, NJ, 3Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 4Leiden University Medical Centre, Leiden, Netherlands, 5IDIS, Complejo Hospitalario Universitario de Santiago, Santiago, Spain, 6School of Medicine, Buenos Aires University, Buenos Aires, Argentina, 7Research Rheumatology Institute n. a. V.A. Nassonova, Moscow, Russian Federation, 8Department of Internal Medicine, University of Genova, Genova, Italy, 9Charité – University Medicine Berlin, Berlin, Germany

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: , ,

Session Information

Date: Tuesday, October 23, 2018

Title: Rheumatoid Arthritis – Treatments Poster III: Biosimilars and New Compounds

Session Type: ACR Poster Session C

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

Background/Purpose:

Sarilumab has shown efficacy in RA both as monotherapy and in combination with csDMARDs in Phase 3 trials. We assessed long-term safety from the sarilumab clinical development program in adult pts with RA who received sarilumab+csDMARD or sarilumab monotherapy from: MOBILITY (NCT01061736); TARGET (NCT01709578); ASCERTAIN (NCT01768572); MONARCH (NCT02332590); ACT11575 (NCT01217814); ONE (NCT02121210); COMPARE (NCT01764997); EASY (NCT02057250); and an ongoing open-label extension EXTEND (NCT01146652), which enrolled pts completing originator studies.

Methods:

Data (cut-off Jan 30, 2018) were pooled from pts on sarilumab+csDMARD (N=2887) or sarilumab monotherapy (N=471). Pts had received sarilumab 200 mg or 150 mg q2w SC, except 151 pts from MOBILITY Part A who received 100 mg qw, 150 mg qw, or 100 mg q2w. Treatment-emergent (TE) adverse events (AEs), AEs of special interest (AESI), and discontinuations were assessed.

Results:

Baseline characteristics were similar between sarilumab+csDMARD and monotherapy pools (mean age 52 yrs; 81–83% female). At baseline, mean RA duration was 9.4 vs 8.3 yrs in combination and monotherapy pools, respectively, with 38.7% vs 8.5% of pts having received prior bDMARDs. Cumulative drug exposure was 7,985.5 vs 798.7 pt-yrs, with maximum duration 7.3 vs 3.5 yrs for sarilumab+csDMARD vs monotherapy, respectively. Exposure-adjusted rates of TEAEs, serious AEs, and TEAEs leading to discontinuations were similar between pools (Table). Infections were the most common AESI. Serious infection event rates were 3.7 vs 1.0/100 pt-yrs for combination vs monotherapy, respectively, and not associated with decreased absolute neutrophil counts (ANC). Incidences of ALT >3x upper limit of normal were 10.3% and 5.5% for sarilumab+csDMARD and monotherapy, and ANC <1.0 Giga/L were 12.7% and 14.9%, respectively. Rates of confirmed GI perforation for combination vs monotherapy were 0.1 vs 0/100 pt-yrs. Analyzing data by 6-month intervals showed no increase in rate over time for serious infections, malignancy, major adverse cardiac events, or ANC <1.0 Giga/L (Figure).

Conclusion:

The long-term safety profile of sarilumab (a human IL-6R blocker recently approved for the treatment of RA), either as monotherapy (observed for >3.5 yrs) or with csDMARD, (observed for >7 yrs) remains stable and consistent with the anticipated profile of an IL-6Rα blocker.

Acknowledgements:

Study funding and medical writing support (Julie Gray, Adelphi Communications) provided by Sanofi and Regeneron Pharmaceuticals, Inc.

Table. Overview of safety analysis from the two pooled data sets sarilumab (any dose) +csDMARD and sarilumab monotherapy (any dose)

 

Sarilumab+csDMARD
(N=2887)

Sarilumab monotherapy
(N=471)

Safety overview: (patients/100 pt-yrs)a

 

TEAEs

2489/1726 (144.2)

386/254.3 (151.8)

Serious TEAEs

685/7270 (9.4)

52/770.4 (6.7)

TEAEs leading to death

31/8187 (0.4)

5/812.3 (0.6)

TEAEs leading to discontinuation

705/8061 (8.7)

53/804.9 (6.6)

AESI: (events/100 pt-yrs)b

Pt-yrs=8187.7

Pt-yrs =812.4

Infections

4451 (54.4)

446 (54.9)

  Serious Infections

301 (3.7)

8 (1.0)

  Opportunistic Infections

76 (0.9)

6 (0.7)

  Herpes zosterc

60 (0.7)

8 (1.0)

  Tuberculosisc

4 (0.0)

1 (0.1)

Leukopeniad

1482 (18.1)

244 (30.0)

Thrombocytopeniad

147 (1.8)

8 (1.0)

Hepatic disorders

726 (8.9)

58 (7.1)

Confirmed GI perforations

9 (0.1)

0

Elevation in lipidsd

498 (6.1)

18 (2.2)

Major adverse cardiovascular eventse

45 (0.5)

2 (0.2)

Hypersensitivity

444 (5.4)

48 (5.9)

  Anaphylaxis

0

0

Injection site reactions

1934 (23.6)

279 (34.3)

Malignancy

56 (0.7)

5 (0.6)

  Malignancy excluding NMSC

38 (0.5)

4 (0.5)

Lupus-like syndrome

5 (0.1)

0

Demyelinating disorders

0

1 (0.1)

GI, gastrointestinal; NMSC, non-melanoma skin cancer; aexposure period is cumulative time at risk of first event; bAESI were investigator reported; exposure period is cumulative total TEAE period; call cases of herpes zoster reported to date were localized; herpes zoster and tuberculosis were reported as opportunistic infections per protocol (not per clinical judgment); dindividual events were reported and laboratory abnormalities were not necessarily persistent; eMACE includes cardiovascular death, myocardial infarction, stroke, hospitalization for either unstable angina and/or transient ischemic attack.


 

 

Disclosure: R. Fleischmann, AbbVie, Amgen, AstraZeneca, BMS, Celgene, EMD-Serano, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sanofi-Genzyme, UCB, 2,AbbVie, ACEA, Amgen, BMS, GSK, Eli Lilly, Novartis, Pfizer, Sanofi-Genzyme, UCB, 5; Y. Lin, Sanofi Genzyme, 1, 3; G. St. John, Regeneron Pharmaceuticals Inc., 1, 3; D. van der Heijde, AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB, 5; C. Qiu, Sanofi Genzyme, 1, 3; J. J. Gómez-Reino, Biogen, Gilead, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, 2, 5; J. A. Maldonado-Cocco, Pfizer, Merck Sharp and Dohme, Sanofi – Aventis, Novartis, Bristol-Myers Squibb, Roche, Boehringer Ingelheim, Schering – Plough, Abbott, UCB, Eli Lilly, Gilead, 5, 8; M. Stanislav, R-Pharm, 5; B. Seriolo, None; G. R. Burmester, AbbVie, Pfizer, UCB, Roche, 2,AbbVie, Eli Lilly, Merck Sharp & Dohme, Pfizer, Sanofi, Roche, UCB, 5, 8.

To cite this abstract in AMA style:

Fleischmann R, Lin Y, St. John G, van der Heijde D, Qiu C, Gómez-Reino JJ, Maldonado-Cocco JA, Stanislav M, Seriolo B, Burmester GR. Long-Term Safety with Sarilumab Plus Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) and Sarilumab Monotherapy in Rheumatoid Arthritis (RA): An Integrated Analysis with 9,000 Patient-Years (Pt-Yrs) of Follow-up [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/long-term-safety-with-sarilumab-plus-conventional-synthetic-disease-modifying-antirheumatic-drugs-csdmards-and-sarilumab-monotherapy-in-rheumatoid-arthritis-ra-an-integrated-analysis-with-9000-p/. Accessed .

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