Rome, Italy—Reducing the dose of biologic in patients with rheumatoid arthritis (RA) is feasible, cost-effective, and does not appear to compromise clinical response, according to separate studies presented at the 2015 annual meeting of the European League Against Rheumatism (EULAR).1,2
The first study found that although reducing the dose of tumor necrosis factor-α (TNF-α) inhibitor by one-third led to more flares of RA, some patients were able to maintain a clinical response after stopping the drug altogether. Moreover, the flares were successfully aborted by restarting the biologic, with no adverse effect on progression of disability.
“The optimal management of RA involves achieving the lowest possible disease activity—ideally remission, and then maintaining this level of control,” stated lead author James Galloway, MD, King’s College Hospital NHS Foundation Trust, United Kingdom, in a EULAR press release. “Our study shows that adopting a TNF inhibitor dose reduction strategy can still meet this objective, with no compromise on symptom control for the patient and offering a more cost-effective option but substantially reducing the high drug costs associated with TNF inhibitor maintenance strategy.”
The OPTTIRA Trial
A biologic disease-modifying antirheumatic drug (DMARD) is typically added on to conventional DMARDs for patients who did not respond, and typically the same doses are used for maintaining response. The first choice of biologic is usually a TNF inhibitor, which has a longer track record in treating RA than newer biologic agents.
OPTTIRA was a 12-month, multicenter, randomized controlled trial designed to evaluate whether reduced doses of a TNF inhibitor (either adalimumab or etanercept) adversely affected response in patients with RA also treated with a conventional DMARD. All patients enrolled in the trial had stable low disease activity (28-joint Disease Activity Score [DAS28] <3.2) for more than 3 months.
Of 227 patients screened for the study, 103 were recruited to participate; 97 were treated during months 0 to 6 while 74 were treated in months 6 to 12.
Over the first 6 months of the study, disease flares were observed in 14% of patients who remained on the same dose of TNF inhibitor, compared with 13% of those tapered by one-third and 37% tapered by two-thirds. Postdose reduction flares were resolved by restarting the TNF inhibitor at the original dose, with no significant differences in self-reported measures of disability on the Health Assessment Questionnaire for either strategy at 6 months.
Among 47 patients who received a reduced dose of TNF inhibitor and then stopped treatment with the biologic after 6 months, 45% (21 of 47) succeeded with no evidence of a flare; their final mean DAS28 after treatment cessation was 2.2, reflecting low disease activity.
Cost Analysis of Tapering
A cost-utility analysis of the controlled, multicenter French STRASS study, also presented at EULAR, found that patients with RA in sustained remission on a biologic remained in remission most of the time on a tapering strategy or after stopping the drug.
Although patients maintained on full-dose biologic had a slightly better clinical course, tapering the drug saved about US $60,000 per quality-adjusted life-year said lead author Antoine Vanier, MD, Université Pierre et Marie Curi, Paris, France. The actual cost-savings over 18 months per patient averaged about US $9500, he said.
A numerically higher percentage of patients in the step-down arm rated their health status as “acceptable” compared with the maintenance arm: 60% versus 44%, respectively. This difference was not statistically significant.
STRASS enrolled 98 adult patients with RA treated with either adalimumab or etanercept for at least a year who maintained a DAS28 <2.6 for at least 6 months and had no radiographic joint progression for at least 12 months. Patients could be on monotherapy or on combination therapy with either methotrexate or leflunomide, and they could also receive up to 5 mg/day of prednisone. Follow-up was 18 months.
Patients were randomized to receive either maintenance therapy with their entry regimen or with a tapering regimen, with the dosing intervals gradually increased to every 3 months (from 14-day intervals with adalimumab or from 7-day intervals with etanercept). Patients who achieved remission on an every-3-month interval stopped treatment completely. Patients with a disease flare (ie, DAS28 ≥2.6) were returned to a more frequent dosing schedule to achieve remission again.
At 18 months, 8 (18%) patients in the step-down arm remained on entry-dosage interval, 19 (43%) maintained remission on a longer dose interval, and 15 (34%) completely stopped their biologic; 2 (5%) patients were off study. In the maintenance arm, all 534 patients remained in the study on remission.
- Galloway JB, Kingsley G, Ma M, et al. Optimising treatment with TNF inhibitors in rheumatoid arthritis with different dose tapering strategies: the OPTTIRA trial. Presented at: 16th Annual European Congress of Rheumatology; June 10-13, 2015; Rome, Italy. Abstract SAT0150.
- Vanier A, Tubach F, Alfaiate T, et al. Step-down strategy of spacing TNF-blockers injections for established rheumatoid arthritis in remission: a cost-utility analysis based on the STRASS trial. Presented at: 16th Annual European Congress of Rheumatology; June 10-13, 2015; Rome, Italy. Abstract OP0280.