Impact of physicians' adherence to treat-to-target strategy on outcomes in early rheumatoid arthritis in the NEO-RACo trial.

OBJECTIVES: It is well recognized that medication adherence of rheumatoid arthritis (RA) patients is often poor. As less attention has been paid to physicians' adherence to targeted treatment, we aimed to investigate how it affects outcomes in aggressively treated early RA patients. METHOD: In the new Finnish RA Combination Therapy (NEO-RACo) trial, 99 patients with early active RA were treated, targeting remission, with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and low-dose prednisolone for 2 years, and randomized to receive infliximab or placebo for the initial 6 months. After 2 years, therapy was unrestricted while remission was still targeted. Patients were divided into tertiles by physicians' adherence to treat-to-target, which was evaluated with a scoring system during the initial 2 years. After 5 years of follow-up, the between-tertile differences in remission rates, 28-joint Disease Activity Score (DAS28) levels, radiological changes, cumulative days off work, and the use of anti-rheumatic medication were assessed. RESULTS: Follow-up data were available for 93 patients. Physicians' good adherence was associated with improved remission rates at 2-4 years and lower DAS28 levels throughout the follow-up. In a multivariable model, physicians' adherence was the most important predictor of remission at 3 months and 2 years (p < 0.001 for both). Between 2 and 5 years, biologics were used more often in the tertile of low adherence compared with the other two groups (p = 0.024). No significant differences were observed in radiological progression and cumulative days off work. CONCLUSIONS: Physicians' good adherence is associated with improved remission rates and lesser use of biologics in early RA.

Cost-effectiveness modelling of sequential biologic strategies for the treatment of moderate to severe rheumatoid arthritis in Finland.

OBJECTIVE: The main objective was to compare the cost-effectiveness of therapeutic options in moderate or severe rheumatoid arthritis (RA) when a clinical response to a first TNF-blocker, either etanercept (ETA), adalimumab (ADA), or infliximab (INF), is insufficient. METHODS: Effectiveness criteria were defined as remission (RS), low disease activity (LDAS), and moderate to high disease activity (MHDAS). Cost-effectiveness was derived as cost per day in RS and in LDAS using simulation modelling to assess six sequential biologic strategies over 2 years. Each sequential treatment strategy was composed of three biologic agents and included a first anti-TNF agent, ETA, ADA or INF, followed by either abatacept (ABA) or rituximab (RTX) as a second therapeutic option in case of an insufficient response, followed by another anti-TNF agent in case of further insufficient response. RESULTS: Over two years and taking into account biologic costs, the following estimated mean costs per day in RS and LDAS were respectively of €829 and €428 for the biologic sequence composed of ADA-ABA-ETA, €1292 and €516 for the sequence ADA-RTX-ETA, €829 and €429 for the sequence ETA-ABA-ADA, €1292 and €517 for the sequence ETARTX- ADA, €840 and €434 for the sequence INF-ABA-ETA, and €1309 and €523 for the sequence INF-RTX-ETA. CONCLUSION: The treatment sequences including ABA as the second biologic option appear more cost-effective than those including RTX in a patients with moderate to severe RA and an insufficient response to a first anti-TNF agent.

Use of the Stanford Health Assessment Questionnaire in estimation of long-term productivity costs in patients with recent-onset rheumatoid arthritis.

OBJECTIVE: To evaluate the utility of the Stanford Health Assessment Questionnaire (HAQ) in the estimation of loss of productivity due to early rheumatoid arthritis (RA) and to develop a simple model for analysis of the cost-benefit of therapies. METHODS: In the Finnish Rheumatoid Arthritis Combination Therapy (FIN-RACo) trial, 162 patients with recent-onset RA who were available for the workforce were randomized to receive either a combination of three disease-modifying anti-rheumatic drugs (DMARDs) or a single DMARD for 2 years and were followed up for 5 years. No biological drugs were used. Data on sick leave and RA-related disability pensions came from official register records. Loss of productivity was computed by both the human capital approach (HCA) and the friction cost approach (FCA). Functional capacity was assessed by the HAQ at baseline and at 6 months. RESULTS: Over 5 years, mean loss of productivity per year was EUR 8344 by the HCA and EUR 1928 by the FCA. The level of the HAQ index at 6 months, but not the change in HAQ from baseline, determined productivity costs. With the HCA, a monotonous association between annual loss of productivity and the 6-month HAQ was found: EUR 2087 [95% confidence interval (CI) 1340-2903] per one step (0.13) on the HAQ scale from 0 to 1.88. With the FCA, the increase in loss of productivity was cut at the HAQ level of 0.5 to 0.75 (EUR 17 740 in 5 years). CONCLUSION: The HAQ index at 6 months may serve as a determinant of long-term RA-related indirect costs in economic analyses in early RA.

Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group.

BACKGROUND: The treatment of rheumatoid arthritis should aim at clinical remission. This multicentre, randomised trial with 2-year follow-up sought evidence on the efficacy and tolerability of combination therapy (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) compared with treatment with a single disease-modifying antirheumatic drug, with or without prednisolone, in the treatment of early rheumatoid arthritis. METHODS: 199 patients were randomly assigned to two treatment groups. 195 started the treatment (97 received combination and 98 single drug therapy). Single-drug therapy in all patients started with sulphasalazine; in 51 patients methotrexate was later substituted. Oral prednisolone was required by 63 patients. The primary outcome measure was induction of remission. Analyses were intention to treat. FINDINGS: 87 patients in the combination group and 91 in the single-therapy group completed the trial. After a year, remission was achieved in 24 of 97 patients with combination therapy, and 11 of 98 with single-drug therapy (p=0.011). The remission frequencies at 2 years were 36 of 97 and 18 of 98 (p=0.003). Clinical improvement (American College of Rheumatology criteria of 50% clinical response) was achieved after 1 year in 68 (75%) patients with combination therapy, and in 56 (60%) using single-drug therapy (p=0.028), while at the 2-year visit 69 and 57 respectively (71% vs 58%, p=0.058) had clinically improved. The frequencies of adverse events were similar in both treatment groups. INTERPRETATION: Combination therapy was better and not more hazardous than single treatment in induction of remission in early rheumatoid arthritis. The combination strategy as an initial therapy seems to increase the efficacy of the treatment in at least a proportion of patients with early rheumatoid arthritis.