Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis: Sixteen-Week Results From a Phase III Randomized, Double-Blind, Placebo-Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors.

OBJECTIVE: To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (SpA) and prior inadequate response to or intolerance of 1 or 2 tumor necrosis factor inhibitors (TNFi). METHODS: In this phase III randomized, double-blind, placebo-controlled trial, adult patients with an inadequate response to or intolerance of 1 or 2 TNFi and an established diagnosis of axial SpA (according to the Assessment of SpondyloArthritis international Society [ASAS] criteria for radiographic axial SpA, with radiographic sacroiliitis defined according to the modified New York criteria and ≥1 feature of SpA) were recruited and randomized 1:1:1 to receive placebo or 80-mg subcutaneous ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W), with an 80-mg or 160-mg starting dose. The primary end point was 40% improvement in disease activity according to the ASAS criteria (ASAS40) at week 16. Secondary outcomes and safety were also assessed. RESULTS: A total of 316 patients were randomized to receive placebo (n = 104), IXEQ2W (n = 98), or IXEQ4W (n = 114). At week 16, significantly higher proportions of IXEQ2W patients (n = 30 [30.6%]; P = 0.003) or IXEQ4W patients (n = 29 [25.4%]; P = 0.017) had achieved an ASAS40 response versus the placebo group (n = 13 [12.5%]), with statistically significant differences reported as early as week 1 with ixekizumab treatment. Statistically significant improvements in disease activity, function, quality of life, and spinal magnetic resonance imaging-evident inflammation were observed after 16 weeks of ixekizumab treatment versus placebo. Treatment-emergent adverse events (AEs) with ixekizumab treatment were more frequent than with placebo. Serious AEs were similar across treatment arms. One death was reported (IXEQ2W group). CONCLUSION: Ixekizumab treatment for 16 weeks in patients with active radiographic axial SpA and previous inadequate response to or intolerance of 1 or 2 TNFi yields rapid and significant improvements in the signs and symptoms of radiographic axial SpA versus placebo.

Reduction of direct and indirect costs in patients with AS receiving etanercept: results from an open-label 36-week extension of the ASCEND study in four European countries.

OBJECTIVE: To characterize the impact of etanercept (ETN) in AS on cost, work productivity and quality of life (QoL). METHODS: A Phase 4, open-label, multi-centre (UK, Scandinavia) extension study in AS. Eligible subjects (n = 84) were treated for 36-52 weeks with ETN 50 mg s.c. once weekly. Analysis included direct costs (transformed out-patient and in-patient care elements), indirect costs (sick leave and lost working days), efficacy and QoL. RESULTS: Annualized direct and indirect costs decreased (55.5%, P ≤ 0.008) during ETN treatment, as did out-patient and in-patient episodes (physiotherapist/physician visits, P = 0.012). Work productivity and QoL increased. CONCLUSION: ETN therapy significantly reduces direct and indirect health-care costs and increases work ability and QoL in AS. Trial Registration. EUDRACT, https://eudract.ema.europa.eu/, 2006-001061-42.

Adalimumab is effective and well tolerated in treating patients with ankylosing spondylitis who have advanced spinal fusion.

OBJECTIVES: To evaluate the effectiveness and safety of adalimumab in treating patients with AS and advanced structural damage. METHODS: Patients with active AS [Bath AS Disease Activity Index (BASDAI) > or =4] received 40 mg of adalimumab every other week plus their standard anti-rheumatic therapies in this 12-week, open-label study. Investigators documented the presence or absence of advanced ankylosis based on previous radiographs. Stages IV (from 50 to <80% involvement in more than two spinal segments) and V (> or =80% spinal involvement, including bamboo spine) disease were considered as advanced AS. Effectiveness parameters included Assessment of SpondyloArthritis international Society (ASAS) criteria, BASDAI response and achievement of optimal sleep. Adverse events were reported throughout therapy and at a 70-day follow-up. RESULTS: The analysis population included 897 patients whose AS was not advanced (i.e. Stages I-III), 31 with Stage IV disease and 41 with Stage V disease. At Week 12, ASAS40/BASDAI 50 responses were achieved by 54%/57% of patients with AS Stages I-III, 48%/58% with AS Stage IV and 54%/66% with AS Stage V, respectively. ASAS partial remission rates were 30, 26 and 7% for patients with Stages I-III, IV and V disease, respectively. Serious infections occurred in three (<1%) patients with AS Stages I-III and in one (1%) patient with AS Stage V. CONCLUSIONS: After 12 weeks of adalimumab therapy, patients with advanced but active AS, including those with structural damage of > or =80% of the vertebrae, achieved improvements in signs and symptoms similar to those attained by patients whose AS was not advanced.

Clustering of symptoms associated with fibromyalgia in a Finnish Twin Cohort.

The objective was to assess the prevalence and heritability of symptoms associated with fibromyalgia in a population-based working-age twin sample. The study was based on the 12,502 like-sexed twins of the Finnish Twin Cohort and 49 diagnosed fibromyalgia patients who answered the same questionnaire in 1990-1992. Questions that were considered to best match symptoms of fibromyalgia were validated between the twins and the fibromyalgia patients. Latent class analysis was used to classify the subjects into more homogeneous groups with respect to the symptom items. The pairwise distribution of symptom classes in relation to zygosity and gender was modelled using quantitative genetic models to estimate heritability. Responses to all fibromyalgia-related items were obtained from 10,608 twins. A similar proportion of men (12%) and women (13%) was placed in the third latent class, which best represented possible fibromyalgia patients. Subjects in this class had a similar symptom profile as the diagnosed fibromyalgia patient group, but they were less severely affected. The two other latent classes represented subjects that were virtually symptom free and subjects with some symptoms. The heritability of liability to symptom class membership was estimated to be 51% (95% CI 45-56%). The prevalence of symptoms associated with fibromyalgia in our population-based sample unselected for disease status was comparable to the prevalence of widespread pain reported in population based studies. The symptoms known to be associated with fibromyalgia seem to have a strong genetic background.