Sustained clinical response and safety of etanercept in patients with early axial spondyloarthritis: 10-year results of the ESTHER trial.

AIMS: Long-term data on TNFi treatment in patients with axSpA is scarce. The objective of this analysis was to assess long-term clinical efficacy of etanercept in early axSpA [including both non-radiographic and radiographic axSpA forms], who participated in the long-term (until year 10) extension of the ESTHER-trial. METHODS: In the previously reported ESTHER-trial, patients with early active axSpA were randomized to treatment with etanercept (n = 40) or sulfasalazine (n = 36) during the first year. Patients in remission discontinued their therapy and were followed up until the end of year 2; in case of remission-loss, etanercept was (re)-introduced and continued until the end of year 10. If remission was not achieved at year 1, patients continued receiving (or were switched to) etanercept for up to 10 years. RESULTS: A total of 19 patients (12 with r-axSpA and 7 with nr-axSpA at baseline) out of the initial 76 patients (= 25%) completed year 10 of the study. In the entire group, a sustained clinical response was seen over 10 years of follow up in the as-observed analysis. Completers were significantly more often male and showed lower values of patient and physician global assessments of disease activity, Ankylosing Spondylitis Disease Activity Score (ASDAS), and Ankylosing Spondylitis Quality of Life questionnaire (ASQoL) scores at baseline as compared with non-completers. When analyzing clinical data of the completers, mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) values were constantly below 2 and mean ASDAS below 2.1 during follow up with no statistically significant differences between the r-axSpA and nr-axSpA subgroups. A total of 39 serious adverse events were documented over the 10 years, while six of them were seen as possibly associated with the etanercept treatment, which led in five patients to treatment discontinuation. CONCLUSION: A sustained clinical response was observed over the 10 years of the study with comparable response and drop-out rates between r-axSpA and nr-axSpA. Etanercept was well tolerated across the entire treatment period and showed a good safety profile with no new safety signals.

Progression of Structural Damage in the Sacroiliac Joints in Patients With Early Axial Spondyloarthritis During Long-Term Anti-Tumor Necrosis Factor Treatment: Six-Year Results of Continuous Treatment With Etanercept.

OBJECTIVE: To evaluate radiographic progression in the sacroiliac (SI) joints and to identify its predictors during long-term treatment (up to 6 years) with the tumor necrosis factor (TNF) inhibitor etanercept in patients with early axial spondyloarthritis (SpA). METHODS: Patients with early axial SpA who were treated with etanercept for up to 6 years in the Etanercept versus Sulfasalazine in Early Axial Spondyloarthritis (ESTHER) trial were selected based on the availability of radiographs of the SI joints. Two readers who were blinded with regard to clinical data scored the radiographs according to the modified New York criteria (range 0-4 per SI joint). A sacroiliitis sum score (total range 0-8) was calculated as the mean of the scores of the 2 readers. Active and chronic inflammatory changes in the SI joints on magnetic resonance imaging (MRI) performed at baseline, year 2, and year 4 were assessed according to the Berlin MRI scoring system. RESULTS: Of the 76 patients originally included in the study, 42 had radiographs of the SI joints available at baseline and at least 1 follow-up time point (year 2, 4, or 6). The mean ± SD change in the sacroiliitis sum score was 0.13 ± 0.73, -0.27 ± 0.76, and -0.09 ± 0.68, in the time intervals baseline to year 2, year 2 to year 4, and year 4 to year 6, respectively. In the longitudinal mixed model analysis, elevated C-reactive protein level (ß = 0.58 [95% confidence interval 0.24, 0.91]) and MRI SI joint osteitis score (ß = 0.06 [95% confidence interval 0.03, 0.10]) were independently associated with progression of the sacroiliitis sum score. CONCLUSION: Our findings indicate that long-term anti-TNF therapy decelerates the progression of structural damage in the SI joints. Elevated CRP level and presence of osteitis on MRI were independently associated with radiographic sacroiliitis progression.

Etanercept is effective as monotherapy or in combination with methotrexate in rheumatoid arthritis: subanalysis of an observational study.

Approximately 30% of patients with rheumatoid arthritis receiving biological disease-modifying antirheumatic drugs (bDMARDs) take them as monotherapy. Although etanercept (ETN) monotherapy has been evaluated in clinical trials, data in the real-world setting are sparse. We compared the efficacy and safety of ETN, given alone or in combination with methotrexate (MTX), in routine clinical practice. This was a subanalysis of patients who received either ETN alone or ETN + MTX during a 52-week prospective, observational study conducted at 329 German centers. The primary endpoint was "Funktionsfragebogen Hannover" (Hannover Functional Ability Questionnaire [FFbH]; low FFbH = worse function) functional remission at week 26 and week 52. Secondary endpoints included the 28-joint count Disease Activity Score (DAS28), DAS28 remission (DAS28 < 2.6), and adverse events (AEs). Participating centers applied ETN monotherapy in 43.1% of patients and ETN + MTX in 56.9%. A smaller proportion of patients achieved FFbH functional remission with ETN vs ETN + MTX (31.9%, 95% confidence interval [CI] 29.1-34.9% vs 39.8%, 37.2-42.5%, respectively; p < 0.001) at 26 weeks and at 52 weeks (38.4%, 35.1-41.7% vs 44.3%, 41.5-47.2%, respectively; p = 0.007). After 52 weeks, the mean DAS28 (±SD) decreased from 5.5 ± 1.3 to 3.4 ± 1.4 (ETN) vs 5.3 ± 1.3 to 3.2 ± 1.3 (ETN + MTX) and DAS28 remission was achieved by 32.5% (95% CI 29.0-36.1%) of patients with ETN vs 38.8% (35.8-41.9%; p = 0.007) with ETN + MTX. Overall, 20.6 (ETN) and 19.7% (ETN + MTX) of patients reported treatment-related AEs. Patients received ETN monotherapy almost as often as ETN + MTX. ETN + MTX appeared marginally more effective than ETN monotherapy in some, but not all, outcomes measured.

Examining patient preferences in the treatment of rheumatoid arthritis using a discrete-choice approach.

BACKGROUND: Biological disease-modifying antirheumatic drugs (bDMARDs) used in second-line treatment of rheumatoid arthritis (RA) are administered parenterally. However, so-called targeted synthetic DMARDs (tsDMARDs) - developed more recently - offer alternative (ie, oral) administration forms in second-line treatment. Since bDMARDs and tsDMARDs can be regarded as equal in terms of efficacy, the present study examines whether such characteristics as route of administration drive RA patients' treatment choice. This may ultimately suggest superiority of some second-line DMARDs over equally effective options, at least according to RA-patient preferences. OBJECTIVE: The current study assessed the importance of oral administration among other treatment characteristics differing between available second-line DMARDs for RA patients' preferences using a discrete-choice experiment (DCE). MATERIALS AND METHODS: The DCE involved scenarios of three hypothetical treatment options in a d-efficient design with varying levels of key attributes (route and frequency of administration, time till onset of drug effect, combination therapy, possible side effects), as defined by focus groups. Further patient characteristics were recorded by an accompanying questionnaire. In the DCE, patients were asked to choose best and worst options (best-worst scaling). Results were analyzed by count analysis and adjusted regression analysis. RESULTS: A total of 1,588 subjects completed the DCE and were eligible for final analyses. Across all characteristics included in the DCE, "oral administration" was most desired and "intravenous infusion" was most strongly rejected. This was followed by "no combination with methotrexate" being strongly preferred and "intake every 1-2 weeks" being strongly rejected. On average, levels of route of administration showed strongest influences on patients' decisions in post hoc bootstrapping analysis. CONCLUSION: According to the results, an oral DMARD that does not have to be combined with methotrexate and is not administered (only) every 1-2 weeks appears a highly favorable treatment option for patients with RA. DMARDs meeting these preferences may increase compliance and adherence in RA treatment.