Biologic-Naive Respond Better to TNF Combination in RA

Damian McNamara

June 16, 2017

MADRID — For people with rheumatoid arthritis (RA), combination treatment with a tumor necrosis factor (TNF) inhibitor and methotrexate appears to be more effective than TNF monotherapy, particularly among those with a history of one or no previous biologic therapies.

"With biologic-naive patients, we have replicated findings in clinical trials and observational analyses from European registries with data from typical clinical practice in the US showing better outcomes in patients on TNF inhibitor combination therapy versus monotherapy," said George Reed, PhD, from Brigham and Women's Hospital in Boston.

"One of the more unique aspects of the analysis was to find this difference diminishing in those with use of one prior biologic and no evidence of a difference in those with two or more prior biologics," he told Medscape Medical News.

For the analysis, Dr Reed and colleagues used data for 1590 patients starting TNF inhibitor therapy from the Corrona Registry, which includes information from 80 rheumatology sites across the United States, including 12 university sites and 68 private practice or affiliated settings. TNF inhibitors in the study included adalimumab, etanercept, infliximab, golimumab, and certolizumab pegol.

Corrona Registry

Treatment of biologic-naive patients favored the combination for achieving low disease activity compared with monotherapy, with an odds ratio of 1.50, "so there is about a 50% better odds of response with the combination," Dr Reed reported here at the European League Against Rheumatism (EULAR) Congress 2017.

For patients with one prior biologic treatment, the results still favored combination therapy (OR, 1.3); however, things were not as clear for those with a history of two or more biologic disease-modifying antirheumatic drugs.

"I got mixed results on the co-primary outcomes, one in favor of monotherapy and one in favor of the combination, and neither was statistically significant," said Dr Reed.

Table. Proportion Achieving Low Disease Activity Stratified by Previous Treatment

Therapy TNF Inhibitor and Methotrexate Combination TNF Inhibitor Monotherapy
Second-line 55.6% 47.1%
Third-line 43.2% 36.6%
Fourth-line 32.0% 34.0%

"The take home message for clinicians is to examine trade-offs of efficacy, safety, and patient preferences between TNF inhibitor combination therapy vs monotherapy in biologic-naive patients given the evidence of better efficacy outcomes," said Dr Reed. "There should be patient-specific reasons for considering monotherapy that overrides these efficacy results."

"In patients who are biologic experienced, there is less evidence of efficacy differences, and monotherapy may be a more likely option," he added.

The take home message for clinicians is to examine trade-offs of efficacy, safety, and patient preferences Dr George Reed

"It's a huge registry. Also, because it's a registry, it is real-world data," said session moderator Jackie Nam, MD, from the Leeds Institute of Rheumatic and Musculoskeletal Medicine in the United Kingdom. "In a real-world study, you realize everyone is so different."

These kinds of studies are useful because "we have patients on monotherapy, combination therapy, and all sorts of things, and it's important to say which groups do better and on what," she said.

An unanswered question, Dr Nam pointed out to Medscape Medical News, is why the biologic-naive group did better with the combination vs monotherapy compared with those who had a history of two or more biologics.

Possible limitations of the study include the retrospective nature of the registry data and inclusion of only 6-month outcomes. Also, the findings are based on prior biologic use and not prior response, Dr Reed said.

Combo Therapy With Janus Kinase Inhibitor

Dr Reed and colleagues performed a similar, secondary analysis comparing the Janus inhibitor tofacitinib (Xeljanz, Pfizer) combination therapy with tofacitinib monotherapy and with TNF inhibitor monotherapy using the Corrona registry data. However, unlike the primary analysis, no significant benefit emerged.

"We found no evidence that outcomes in tofacitinib monotherapy were different in patients who had a history of one or more prior biologics" in either comparison, he reported.

Because there is no evidence that tofacitinib monotherapy is less effective than tofacitinib combination therapy or TNF inhibitor combination therapy in the outcome measures evaluated, "monotherapy may be a more likely option," said Dr Reed.

However, more research is needed, he added. "Until there is sufficient evidence in biologic-naive patients, the outcomes in tofacitinib monotherapy vs either tofacitinib combination therapy or TNF inhibitor combination therapy are not known."

Going forward, Dr Reed said he would like to investigate whether the use of combination therapy vs monotherapy for either TNF inhibitors or tofacitinib alters the use of prednisone in this patient population over time. Another next step would be to compare long-term safety of monotherapy vs combination treatment for both treatments to further inform clinical decision-making, he told Medscape Medical News.

Dr Reed is an employee and shareholder of Corrona LLC, the study sponsor (Pfizer) provided funding for editorial support. Dr Nam has disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2017: Abstract OP0022. Presented June 14, 2017.

Follow Medscape Rheumatology on Twitter @MedscapeRheum and Damian McNamara @MedReporter

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