SAN FRANCISCO – Patients who initiate triple therapy for rheumatoid arthritis appear to have lower persistence in filling the prescriptions and lower adherence to the regimen even when prescriptions are dispensed for the drugs, compared with users of combination therapy with a tumor necrosis factor inhibitor plus methotrexate in two Veterans Affairs studies.
The studies also suggest that the similar efficacy and patient adherence for both triple therapy and combination therapy with a tumor necrosis factor inhibitor (TNFi) plus methotrexate that have been observed in randomized controlled trials (RCTs) do not accurately portray what occurs in real-world clinical practice.
Dr. Brian C. Sauer
In one study, Brian C. Sauer, Ph.D., of the University of Utah, Salt Lake City, and coinvestigators utilized the historical data available for utilized the historical data available for 4,364 U.S. veterans over 28 years of age treated for RA from 2006 through 2012. Patients needed to be enrolled with Veterans Affairs for about 6 months prior to and 12 months after the initiation of the triple therapy. The triple therapy involved 3,204 patients. The three drugs could be initiated concomitantly, in an approach that is typical of an RCT design, or could be introduced at different times, with the requirement of an overlapping period of use of all three. For the combination therapy used in 1,160 patients, the two drugs needed to overlap by at least 1 day. When various algorithms that accounted for clinician-mandated shifts in drug use according to patient response to treatment were used, the persistence outcomes could be calculated, with patients judged to be adherent or nonadherent to either treatment regimen.
At 12 months, the rate of persistence in staying on triple therapy ranged from 29% to 50% and for TNFi/methotrexate from 42% to 59%, according to three definitions of persistence the investigators used. Adherence of greater than 80% during the year to the regimens occurred in 17% on triple therapy and 24% on TNFi/methotrexate. The advantage for the combination therapy persisted when factors likely to affect treatment choice and persistence were accounted for in propensity scoring of 1,143 patients from each group.
“We did not evaluate early side effects. Our study focused on 1-year persistence. Similar early drop-off between the groups and RCTs suggest that the treatments have similar tolerability. The fact that patients on triple therapy appeared to be sicker also suggests that providers are possibly concerned about TNF [inhibitor] side effects in the population treated with triple therapy,” Dr. Sauer said at the annual meeting of the American College of Rheumatology.
The additional complexity of triple therapy might also have contributed to the lower adherence, he said.
A second, similar VA study that was presented at the meeting examined patients who had an inadequate response to methotrexate monotherapy found similar results in a comparison of 2,125 patients who added a TNFi to methotrexate with 171 patients who added sulfasalazine and hydroxychloroquine, a scenario that has been tested in RCTs. In this study, 18% persisted in staying on triple therapy over a year, compared with 43% on TNFi/methotrexate, while 12-month adherence rates were 11% and 25%, respectively.
Dr. Sauer reported financial disclosures involving research grant support from Amgen.