ROME – Patients with rheumatoid arthritis in sustained remission on a biologic drug successfully remained in remission most of the time while gradually stepping down to a longer dosage interval or eventually going off the biologic entirely in a controlled, multicenter French trial with 98 patients followed for 18 months.
Mitchel L. Zoler/Frontline Medical News
Dr. James R. O'Dell
The results also showed that while patients who were maintained throughout 18 months on full biologic-drug dosage fared slightly better clinically, the taper-down strategy saved an average 53,417 euro (about $60,000 US) for each quality-adjusted life-year (QALY) decrement caused by the step-down treatment, Dr. Antoine Vanier reported at the European Congress of Rheumatology. The actual decrement in QALYs among the 44 patients randomized to the step-down arm during the 18 month study averaged 0.158 QALYs, compared with the 54 patients maintained on full dose. The actual cost savings over 18 months averaged 8,440 euro (about $9,500 US) per patient, said Dr. Vanier, a rheumatologist and biostatistician at Pierre and Marie Curie University in Paris.
In addition, a numerically larger percentage of patients in the step-down arm, 61%, rated their health status “acceptable,” compared with 44% among those in the maintenance arm, although this difference was not statistically significant.
The Spacing of TNF-blocker Injections in Rheumatoid Arthritis Study (STRASS) enrolled adult rheumatoid arthritis patients on subcutaneous treatment with either 40 mg adalimumab (Humira) every 14 days or 50 mg etanercept (Enbrel) every 7 days for at least a year and who maintained a 28-joint disease activity score (DAS28) of 2.6 or below for at least 6 months and had no radiographic joint progression for at least a year. Patients could be on either monotherapy with one of these biologic drugs or on a stable regimen that also included either methotrexate or leflunomide, and patients could also receive up to 5 mg/day prednisone.
The researchers randomized patients to either maintain their entry regimen or start on a program that serially increased the time between biologic injections every 3 months. The adalimumab dosing interval increased to a 40-mg injection every 21 days, 28 days, 42 days, and then patients who remained in remission with an injection every 42 days for 3 months stopped adalimumab treatment entirely. Among the etanercept patients, the between-dose intervals increased to 10 days, 14 days, 21 days, and then a complete stop. Patients who experienced a flare, with their DAS28 rising above 2.6, returned to a more frequent dosing interval able to lower their DAS28 to 2.6 or less once again and regain remission.
After 18 months, 8 (18%) patients in the step-down arm remained on their entry-dosage interval, 19 (43%) patients maintained remission on a lengthened-dosing interval, 15 (34%) patients completely stopped their biologic, and 2 (5%) patients had left the study. In the maintenance arm, all 54 patients remained in the study and in remission on their entry-dosage schedule.
A majority of the patients in the step-down arm remained on their reduced- or no-dose regimen after the trial completed, noted Dr. Bruno Fautrel, senior investigator of STRASS and professor of rheumatology at Pierre and Marie Curie University, Paris. The researchers have so far not been able to identify any patient-specific features to prospectively identify the patients most likely to successfully undergo biologic step-down, Dr. Fautrel added.
Despite this uncertainty as to which patients are best suited to a step-down strategy, the possibility of successfully stepping-down biologic treatment for most RA patients to save on drug costs without compromising patient outcomes makes it “worth considering” on a case-by-case basis, Dr. Vanier said.
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