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1888 Biologic Disease-Modifying Antirheumatic Drugs and Risk of Multiple Myeloma

Program: Oral and Poster Abstracts
Session: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster I
Hematology Disease Topics & Pathways:
Diseases, autoimmune disorders, multiple myeloma, Biological, antibodies, Adult, Therapies, Immune Disorders, Plasma Cell Disorders, Study Population, Lymphoid Malignancies, Clinically relevant
Saturday, December 1, 2018, 6:15 PM-8:15 PM
Hall GH (San Diego Convention Center)

Gregory Sampang Calip, PharmD, MPH, PhD1,2*, Karen Sweiss, PharmD3,4, Sruthi Adimadhyam, BPharm, MS5, Alemseged Ayele Asfaw, MSc, B Pharm5*, Jifang Zhou, MD5, Zhaoju Wu, MD, PhD5*, Todd Lee, PharmD, PhD5*, Brian C.-H. Chiu, PhD6 and Pritesh Patel, MD3,7

1Division of Public Health Sciences, Epidemiology Program, Fred Hutchinson Cancer Research Center, Seattle, WA
2Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, IL
3University of Illinois Cancer Center, Chicago, IL
4Department of Pharmacy Practice, University of Illinois at Chicago, Hinsdale, IL
5Department of Pharmacy Systems, Outcomes and Policy, University of Illinois at Chicago, Chicago, IL
6Department of Public Health Sciences, University of Chicago, Chicago, IL
7Division of Hematology/Oncology, University of Illinois at Chicago, Chicago, IL

INTRODUCTION: Biologic disease-modifying antirheumatic drugs (DMARDs) are used more frequently and earlier in the course of rheumatologic conditions in a treat-to-target approach. These medications act on proteins and cytokines with potential pro- and anti-malignancy roles, including tumor necrosis factor-alpha (TNF), human interleukin (IL) receptors and B- and T-cell functions. There is concern for hematologic malignancy with some but not all biologic DMARDs. Little is known about possible associations between these medications and development of multiple myeloma (MM). Our purpose was to determine risk of MM in relation to biologic DMARD treatment, duration of use and by biologic target in a large cohort of patients with rheumatologic conditions.

METHODS: We conducted a nested case-control study within a cohort of adults undergoing active treatment for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Patients were sampled from a population of commercially-insured U.S. health plan enrollees in the Truven Health MarketScan Research Database between 2009 and 2015. MM cases were ascertained using validated algorithms for administrative data. Up to ten controls from the overall cohort were matched to each MM case on age, sex and rheumatologic indication using incidence density sampling with replacement. Index date was defined as the date of MM diagnosis for a case and corresponding time at-risk for matched controls. Exposure was defined as both treatment and duration of biologic DMARD use including TNF inhibitor (etanercept, infliximab, adalimumab, golimumab, certolizumab pegol), IL-6 receptor antagonist (tocilizumab), T-cell targeted (abatacept) and B-cell depleting (rituximab) agents and were determined from health claims and pharmacy dispensing data. Data on rheumatologic indication, comorbid conditions and treatment with prescription nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids and conventional synthetic DMARDs (hydroxychloroquine, sulfasalazine, methotrexate, leflunomide) were documented in the 12 month baseline period and during follow up as potential confounders. An exposure lag time of 365 days was used to minimize protopathic bias. Multivariable conditional logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for risk of MM associated with biologic DMARDs.

RESULTS: From a retrospective cohort of 56866 adult patients with rheumatologic conditions, 287 MM cases and 2760 matched controls were identified. Compared to controls, a higher proportion of cases had Charlson comorbidity scores of 2 or greater (24% vs 18%) and used oral corticosteroids during follow up (67% vs 61%). Cases and controls were similar with respect to use of prescription NSAIDs (56% vs 59%) and use of conventional DMARDs (63% vs 67%). Use of biologic DMARDs overall was similar between cases and controls (14% vs 15%), although cases had a slightly lower proportion of etanercept users (5% vs 7%) and a slightly higher proportion of tocilizumab users (1.4% vs 0.4%). Biologic DMARD users were younger, more likely to have psoriatic arthritis or ankylosing spondylitis, lower comorbidity and greater use of concomitant NSAIDs and oral corticosteroids.

Risk of MM was neither associated with biologic DMARD use overall (OR 0.84; 95% CI 0.57, 1.26; P=0.40) nor with longer duration of biologic DMARD use (>2.5 years: OR 0.72; 95% CI 0.34, 1.52; P=0.39). However, compared to patients treated with only conventional DMARDs, those receiving concomitant conventional plus biologic DMARDs had a 48% lower risk of developing MM (OR 0.52; 95% CI 0.30, 0.88; P=0.02). Associations with MM appeared to differ by specific biologic DMARD agent with estimates suggesting a lowered risk of MM with use of etanercept (OR 0.55; 95% CI 0.30, 1.02; P=0.06) and greater risk with use of tocilizumab (OR 4.33; 95% CI 1.33, 14.19; P=0.02) that was statistically significant, although confidence intervals were wide.

CONCLUSIONS: The potential influence of biologic DMARDs on multiple myeloma is complex. We found that immune suppression with conventional plus biologic DMARDs is inversely associated with MM risk in patients with rheumatologic conditions, but this association differed by biologic drug target. Further research is needed to understand the roles of DMARDs targeting TNF and IL-6 in relation to subsequent myeloma pathogenesis.

Disclosures: Patel: Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Honoraria.

*signifies non-member of ASH