Safety of Biologic and Non-Biologic Disease-Modifying Antirheumatic Drug (DMARD) Therapy in Veterans with Rheumatoid Arthritis and Chronic Hepatitis C Infection

Jeffrey R. Curtis^1,2, Mary Jane Burton³, Shou Yang¹, Lang Chen¹, Ted R. Mikuls⁴, Jasvinder A. Singh², Kevin L. Winthrop⁵ and John Baddley^2,6, ¹University of Alabama at Birmingham, Birmingham, AL, ²Birmingham VAMC, Birmingham, AL, ³Jackson VAMC, Jackson, MS, ⁴University of Nebraska Medical Center, Omaha, NE, ⁵Oregon Health and Science University, Portland, OR, ⁶Medicine, University of Alabama at Birmingham, Birmingham, AL

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Biologic agents, Hepatitis C and rheumatoid arthritis (RA)

Session Information

Date: Monday, November 9, 2015

Title: Rheumatoid Arthritis - Clinical Aspects Poster II

Session Type: ACR Poster Session B

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

Background/Purpose: Among patients with rheumatoid arthritis and hepatitis C virus (HCV) infection, the impact of biologic and nonbiologic DMARD therapy on hepatotoxicity has received limited study.

Methods: Using 1997-2011 national data from the US Veteran’s Health Administration, we identified a cohort of 38,433 rheumatologist-diagnosed RA patients. Eligible patients had HCV infection (defined by detectable HCV RNA) and subsequently initiated a new biologic (infliximab, adalimumab, etanercept; rituximab) or nonbiologic (hydroxychloroquine, sulfasalazine, methotrexate, leflunomide) DMARD that they had never been on previously. Patients were required to have a baseline ALT <66 IU/mL and quantifiable HCV RNA within 90 days prior to starting biologic/DMARD therapy (defined as “index date”) as well as ALT and HCV RNA measurement within 1 year after index date. Patients with HIV and hematologic malignancy were excluded. Patients could contribute more than one treatment episode provided they switched to a new biologic/DMARD they had not previously used, or switched to a previously used biologic/DMARD they had not used in the past year. The primary outcome of interest was hepatotoxicity, defined as ALT elevation ≥100 IU/L (corresponding to 3x ULN for women and 2.5x ULN for men) or increase in HCV RNA by one log, and was examined within the first year of biologic/DMARD use. Current exposure was defined as-treated based on day supply (injection biologics) or usual dosing intervals (infused biologics).Results were reported as the cumulative incidence of patients achieving pre-defined hepatotoxicity at 3, 6 and 12-months post-biologic exposure.

Results:

RA patients with HCV (n=748) were identified and contributed 1097 biologic/DMARD treatment episodes. Mean age was 59.8 years and 77.3% were male. Nearly half of biologic users (47.4%) were also prescribed methotrexate and/or leflunomide. Overall, ALT elevations were uncommon, with 37 hepatotoxicity events (ALT ≥100 IU/L or HCV RNA increase by one log) occurring within 12 months (3.4%). Treatment episodes with biologics demonstrated increased frequency of hepatotoxicity (ALT ≥100 IU/L or HCV RNA increase by one log) than nonbiologics (4.8% vs 2.3%, p=0.028). Most hepatotoxicity events occurred within 6 months of DMARD initiation (29/37, 78%).

Table: Cumulative hepatotoxicity events among RA patients with HCV within 12 months of initiating biologic/nonbiologic DMARDs

		Cumulative Hepatotoxicity Events
Drug	Number exposed	3-months	6-months	12-months
ADA	180	3(1.7%)	7(3.9%)	8(4.4%)
ETA	179	4(2.2%)	7(3.9%)	10 (5.6%)
INF	48	0(0%)	2(4.2%)	2(4.2%)
RIT	28	1(3.6%)	1(3.6%)	1 (3.6%)
ABA	22	0(0%)	1(4.6%)	1(4.6%)
LEF	91	1(1.1%)	2(2.2%)	2(2.2%)
MTX	156	0(0%)	4(2.6%)	6(3.9%)
HCQ	272	2(0.7%)	2(0.7%%)	4(1.5%)
SSZ	121	3(2.5%)	3(2.5%)	3(2.5%)
Total	1097	14(1.3%)	29(2.6%)	37(3.4%)

ADA=adalimumab; ETA=etanercept; INF=infliximab; RIT=rituximab, ABA=abatacept;

LEF=leflunomide; MTX=methotrexate; SSZ-HCQ=sulfasalazine/hydroxychloroquine

Conclusion: In US Veterans with HCV and RA receiving biologic and nonbiologic DMARDs, the frequency of treatment-related hepatotoxicity (ALT ≥100 IU/L) was low, with a higher frequency observed in treatment episodes with current biologic use. The majority of hepatotoxicity events occurred within 6 months after biologic/DMARD initiation.

Disclosure: J. R. Curtis, Roche/Genentech, UCB, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, AbbVie, 2,Roche/Genentech, UCB, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, AbbVie, 5; M. J. Burton, None; S. Yang, None; L. Chen, None; T. R. Mikuls, None; J. A. Singh, None; K. L. Winthrop, BMS, 2,AbbVie, BMS, UCB, Amgen, 5; J. Baddley, Pfizer, Astellas, Merck, 5,BMS, 2.

To cite this abstract in AMA style:

Curtis JR, Burton MJ, Yang S, Chen L, Mikuls TR, Singh JA, Winthrop KL, Baddley J. Safety of Biologic and Non-Biologic Disease-Modifying Antirheumatic Drug (DMARD) Therapy in Veterans with Rheumatoid Arthritis and Chronic Hepatitis C Infection [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/safety-of-biologic-and-non-biologic-disease-modifying-antirheumatic-drug-dmard-therapy-in-veterans-with-rheumatoid-arthritis-and-chronic-hepatitis-c-infection/. Accessed .

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