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In RA TNF-Inhibitors Prove To Be Durable Choice

Patients with rheumatoid arthritis (RA) were less likely to discontinue their first biologic when that treatment was a tumor necrosis factor (TNF) inhibitor than if it was a non-TNF biologic, and especially if treatment was initiated prior to 2005.

Of the 2,281 patients starting on their first biologic -- 97.5% of whom started on an anti-TNF agent -- 48% (95% CI 0.34-0.69) discontinued their first biologic at a median time to discontinuation of 4.1 years, reported Kaleb Michaud, PhD, of the University of Nebraska in Omaha, and colleagues.

Of some 1,097 patients who started on a second biologic, 49% discontinued treatment at a median time to discontinuation of 3.3 years, they wrote in RMD Open -- Rheumatic & Musculoskeletal Diseases.

For the first biologic, the annual discontinuation rate was 17%, and this was significantly higher in patients who started a biologic in 2005 or later compared with those who started a biologic before 2005 (25% versus 16%,P=0.005), respectively.

If a second biologic was initiated the annual discontinuation rate was 20%, and it was again higher in patients who started treatment in 2005 or later.

The annual discontinuation rate was significantly lower with etanercept (Enbrel) at 14% and adalimumab (Humira) at 18% compared with infliximab (Remicade), with a discontinuation rate of 26%.

"The present study shows that patients with RA tend to remain on their initial biologic for relatively long periods, a proxy for effectiveness, though having increased options for biologic treatment is associated with increased discontinuation rates," the authors wrote.

Patients were enrolled in the National Data Bank for Rheumatic Diseases (NDB), a longitudinal observational study of rheumatic disease outcomes.

Eight biologics were included in the study. Among TNF inhibitors were infliximab, etanercept, adalimumab, golimumab (Simponi), and certolizumab pegol (Cimzia). Non-TNF biologics were rituximab (Rituxan), tocilizumab (Actemra), and abatacept (Orencia).

Almost one-quarter of patients started their first biologic after 2005, and half of the participants started their second biologic after that date. Importantly, 97% of patients who started a non-TNF inhibitor did so after 2005, the authors noted.

Throughout follow-up, the likelihood of discontinuing a TNF inhibitor as first biologic was lower than a non-TNF agent, with an adjusted hazard ratio of 0.49 (95% CI 0.34-0.71), the researchers reported.

From 2005 onward, the adjusted HR for discontinuation of the first biologic was 0.60 (95% CI 0.41-0.90).

The risk of discontinuing the second biologic throughout the study period was 32% lower when the second biologic was again a TNF inhibitor (adjusted HR 0.68, 95% CI 0.51-0.90).

However, "when analyses were restricted to biologics started in 2005 or later, there was no longer a significant difference between the two treatment options," Michaud and colleagues noted.

Among patients who discontinued their first biologic, 40% cited side effects as the reason for discontinuing treatment, 27% reported a lack of efficacy, and 11% said the reason was cost.

"Patients discontinuing due to a side effect had the highest annual discontinuation rates at 63% in one year," the investigators observed, "followed by those who discontinued due to inefficacy at 47% in one year."

More patients (16%) discontinued their second biologic because of cost, but fewer (32%) discontinued treatment because of side effects.

However, overall discontinuation rates with the second biologic were higher at 81% a year for side effects and 57% for lack of efficacy.

"In order to inform treatment choice, it is also important to identify predictors of discontinuation," the researchers wrote.

In the current analysis, smoking, comorbidities, and worse overall health were predictors of patients discontinuing their first biologic, while a protective effect was seen for concomitant methotrexate.

Limitations of the study include the relatively low number of patients on a non-TNF inhibitor as both a first and second biologic, making comparisons between drug classes challenging. There may also be differences between European and American patients due to different prescribing patterns and reimbursement policies, the authors observed.

"Our findings help provide context for why patients might stop their biologics and factors for rheumatologists to consider when making treatment decisions," they concluded. "But there is still the unmet need to clearly identify the patients who will not respond to a specific therapy," and for whom "a different drug class would lead to a lower discontinuation rate, eventually reflecting a higher effectiveness."

This study was partially funded by Immunex, a subsidiary of Amgen, and by Wyeth/Pfizer. Michaud disclosed support from Rheumatology Research Foundation Investigator Award. Co-authors disclosed multiple relevant industry relationships, including Amgen, Pfizer, Abbott, Astra-Zeneca, Bristol-Myers Squibb, Centocor, Chugai, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Otsuka, Roche, sanofi aventis, Schering Plough, UCB and Wyeth.

This article is brought to our readers by our friends at MedPage Today. It was originally published on November 30, 2105. 

Disclosures: 
The author has no conflicts of interest to disclose related to this subject

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