Switch to Biologic for RA More About Prescribers Than Patients

Janis C. Kelly

December 11, 2019

The length of time a patient with rheumatoid arthritis (RA) takes a conventional synthetic disease-modifying antirheumatic drug (csDMARD) such as methotrexate before switching to a biologic DMARD varies widely, and the variation is largely related to differences in prescriber preference, researchers say.

They found that 65% of the variation was attributed to differences between prescribers rather than patient variables. Another 4.6% was associated with regional differences in biologic DMARD use, and 30.4% of the variation was unexplained.

"Although disparities in access to biologic DMARDs increased in this study, the overall prescription percentage decreased relative to the population of active medication users with RA. This suggests that despite rheumatologists prescribing fewer biologic DMARDs on average per patient per unit of time, variations in the prescription of biologic DMARDs continue to grow," the researchers explain.

The clinical implications of these differences in prescriber preferences are unclear, but the findings "show that between-prescriber differences exist in health care delivery for patients with RA, despite identical health insurance coverage," they continue.

Mark Tatangelo, BA, Claire Bombardier, MD, and colleagues at the University of Toronto published their findings online December 6 in JAMA Network Open.  

They examined factors associated with the length of time from first csDMARD to receipt of first biologic in a retrospective cohort study using administrative data for 17,672 patients with RA and identical single-payer health insurance coverage in Ontario, Canada.

Patients were aged 67 years or older, had incident RA, and had received at least one csDMARD. The observation window was 2002 to 2015. During the study 719 patients (4.1%) received a first biologic DMARD. The primary outcome was time from first csDMARD to receipt of first biologic DMARD.

In an invited commentary, Natalie McCormick, PhD, from the Clinical Epidemiology Program at Massachusetts General Hospital in Boston, writes, "A distinctive feature of the report by Tatangelo et al was the emphasis on longer time to initiation of biologic therapy as an ideal outcome."

Factors associated with a quicker move from csDMARDs to biologic DMARDs included younger age, female sex, living in an urban area close to prescribers, and longer disease duration. The shift to biologic DMARDs was also earlier for prescribers who were more recent graduates, in urban areas, and in areas with a greater supply of rheumatologists.

McCormick suggests that the association between earlier biologic DMARD use and higher concentration of rheumatologists might indicate that "peer effects" influence prescribing decisions.

Factors associated with a more prolonged time on csDMARDs before beginning a biologic DMARD included older age, male sex, and distance to the nearest rheumatologist.

Immigrants born outside of Canada were 41% less likely to have begun biologic DMARDs. "While its mechanism and implications warrant further investigation, this finding is novel and compelling, and it could become increasingly important," McCormick writes.

The variation in highest biologic DMARD use compared with lowest use among the regions in Ontario rose from 1.8% in 2002 to 8.7% in 2015. In models adjusted for age, sex, calendar year, and all patient and physician covariates, regional differences accounted for 4.6% of the variation in biologic DMARD prescription.

"A 4.6% difference in time to receipt of biologic DMARDs between regions should be considered problematic in the absence of other explanatory factors," the authors write. "For example, every 1% increase in biologic prescriptions among a population of 72,000 funded patients with RA costs approximately CaD $10.8 million (US $8.25 million) per year (assuming 10% biologics penetration and CaD $15,000 annually per biologic DMARD prescription [US $11,460])."

They explain that reducing the highest spending region in Ontario to the average spend would save approximately CaD $6 million to $8 million (US $4.6 million to $6.1 million) per year, whereas increasing biologic use in the underserved regions to the population average would cost about CaD $6 million to $8 million (US $4.6 million to $6.1 million).

McCormick writes that both undertreatment and overtreatment need more study and adds that the age gradient identified in this study "may reflect an ongoing bias against prescribing biologic DMARDs to elderly patients, despite a lack of evidence that older patients have a higher risk of infections or other adverse events."

McCormick and the researchers emphasize that the decision to begin biologic DMARDs should not be taken lightly. "[S]mall changes in time to first biologic DMARD have major clinical and economic impacts. From a clinical perspective, the prescription of a biologic DMARD represents a transition to a more complex care plan, with less data to support the next prescription choice after the first biologic DMARD," the authors warn.

This study was funded by grants from the Canadian Institute of Health Research, the Arthritis Society, the Ontario Drug Policy Research and Effectiveness Network, and the Canadian Institute of Health Research Drug Safety and Effectiveness Network. This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care.

Several study authors report receiving consulting fees from Amgen, Covance, Roche, Novartis, Sanofi, Merck, and Eli Lilly and Co; grants and consulting fees from AbbVie, Janssen Pharmaceuticals, Hospira, Merck, Pfizer, Sanofi, and Novartis; and grants from Amgen, Eli Lilly and Co, Celgene, Medexus, Medreleaf, Roche, and Union Chimique Belge.

McCormick reports a fellowship award from the Canadian Institutes of Health Research.

JAMA Network Open. Published online December 6, 2019. Full text, Editorial

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