Secukinumab versus adalimumab for psoriatic arthritis: comparative effectiveness up to 48 weeks using a matching-adjusted indirect comparison

Secukinumab and adalimumab are approved for adults with active psoriatic arthritis (PsA). In the absence of direct randomized controlled trial (RCT) data, matching-adjusted indirect comparison can estimate the comparative effectiveness in anti-tumor necrosis factor (TNF)-naïve populations. Individual patient data from the FUTURE 2 RCT (secukinumab vs. placebo; N = 299) were adjusted to match baseline characteristics of the ADEPT RCT (adalimumab vs. placebo; N = 313). Logistic regression determined adjustment weights for age, body weight, sex, race, methotrexate use, psoriasis affecting ≥ 3% of body surface area, Psoriasis Area and Severity Index score, Health Assessment Questionnaire Disability Index score, presence of dactylitis and enthesitis, and previous anti-TNF therapy. Recalculated secukinumab outcomes were compared with adalimumab outcomes at weeks 12 (placebo-adjusted), 16, 24, and 48 (nonplacebo-adjusted). After matching, the effective sample size for FUTURE 2 was 101. Week 12 American College of Rheumatology (ACR) response rates were not significantly different between secukinumab and adalimumab. Week 16 ACR 20 and 50 response rates were higher for secukinumab 150 mg than for adalimumab (P = 0.017, P = 0.033), as was ACR 50 for secukinumab 300 mg (P = 0.030). Week 24 ACR 20 and 50 were higher for secukinumab 150 mg than for adalimumab (P = 0.001, P = 0.019), as was ACR 20 for secukinumab 300 mg (P = 0.048). Week 48 ACR 20 was higher for secukinumab 150 and 300 mg than for adalimumab (P = 0.002, P = 0.027), as was ACR 50 for secukinumab 300 mg (P = 0.032). In our analysis, patients with PsA receiving secukinumab were more likely to achieve higher ACR responses through 1 year (weeks 16-48) than those treated with adalimumab. Although informative, these observations rely on a subgroup of patients from FUTURE 2 and thus should be considered interim until the ongoing head-to-head RCT EXCEED can validate these findings. Novartis Pharma AG

Durability of Therapeutic Response to Milnacipran Treatment for Fibromyalgia. Results of a Randomized, Double-Blind, Monotherapy 6-Month Extension Study

To evaluate the durability of improvement and long-term efficacy of milnacipran treatment in fibromyalgia, to assess efficacy in patients re-randomized from placebo to milnacipran, and to collect additional information on the tolerability and efficacy of long-term treatment with milnacipran.A total of 449 patients who successfully completed a 6-month lead-in study enrolled in this 6-month extension study (87.7% of eligible subjects). Patients initially receiving milnacipran 200 mg/day during the lead-in study were maintained at 200 mg/day (n = 209); patients initially assigned to placebo or milnacipran 100 mg/day were re-randomized (1:4) to either 100 mg/day (n = 48) or 200 mg/day (n = 192) of milnacipran for an additional 6 months of treatment. Efficacy assessments included visual analog scale pain ratings, Fibromyalgia Impact Questionnaire (FIQ) total score, and Patient Global Impression of Change (PGIC).Patients continuing on milnacipran demonstrated a sustained reduction in pain over the full 12-month period. Additional beneficial effects were also maintained, as indicated by the PGIC and FIQ. Patients initially assigned to either placebo or milnacipran 100 mg/day in the lead-in study and subsequently re-randomized to milnacipran 200 mg/day in the extension study experienced further improvements in their mean pain scores, FIQ total scores, and PGIC ratings at 1 year. Milnacipran treatment was generally well tolerated. The most commonly reported newly emergent adverse event was nausea.In addition to confirming that milnacipran safely and effectively improves the multiple symptoms of fibromyalgia, these data indicate that milnacipran provides 1-year durable efficacy in this patient population.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78636/1/j.1526-4637.2009.00755.x.pd

Prediction and benefits of minimal disease activity in patients with psoriatic arthritis and active skin disease in the ADEPT trial

Objectives: To determine the proportion of patients with psoriatic arthritis in the Adalimumab Effectiveness in Psoriatic Arthritis trial achieving minimal disease activity (MDA) and its individual components at 1 or more visits over 144 weeks, identify baseline predictors of MDA achievement, and evaluate the association of MDA status with independent quality of life (QoL)-related patient-reported outcomes (PROs). Methods: Univariate and multivariate analyses were used to identify the baseline characteristics that predicted achievement of MDA at individual time points (weeks 12 through 144) or sustained MDA (achievement of MDA at 2 consecutive time points 12 weeks apart). The association of independent QoL-related PROs with MDA achievement was evaluated at weeks 24 and 144. Results: In univariate analyses, higher baseline patient assessment of pain, tender joint count (TJC), enthesitis and Health Assessment Questionnaire-Disability Index (HAQ-DI) score were significantly associated with lower likelihood of achieving MDA at later time points. Multivariate analyses confirmed higher baseline HAQ-DI as a significant predictor for failure to achieve MDA at later time points. Achievement of sustained MDA was associated with lower baseline TJC and HAQ-DI score. Achievement of different MDA components appeared to be treatment dependent. MDA achievers had significantly better QoL-related PROs and greater improvements in PROs from baseline to week 24 compared with non-achievers. Conclusions: Higher HAQ-DI score was the most consistent baseline factor that decreased the likelihood of achieving MDA and sustained MDA at later time points. Achieving MDA was associated with better independent QoL-related PROs

Secukinumab sustains improvement in signs and symptoms of psoriatic arthritis: 2 year results from the phase 3 FUTURE 2 study

Objectives. To assess long-term efficacy, safety and tolerability of secukinumab up to 104 weeks in patients with active PsA. Methods. Patients with PsA (n = 397) were randomized to s.c. secukinumab 300, 150 or 75 mg or placebo at baseline, weeks 1, 2, 3 and 4 and every 4 weeks thereafter. Placebo-treated patients were re-randomized to receive secukinumab 300 or 150 mg s.c. from week 16 (placebo non-responders) or week 24 (placebo responders). Exploratory endpoints at week 104 included 20, 50 and 70% improvement in ACR criteria (ACR20, 50, 70); 75 and 90% improvement in the Psoriasis Area Severity Index, 28-joint DAS with CRP, presence of dactylitis and enthesitis and other patient-reported outcomes. For binary variables, missing values were imputed; continuous variables were analysed by a mixed-effects model for repeated measures. Results. A total of 86/100 (86%), 76/100 (76%) and 65/99 (66%) patients in the secukinumab 300, 150 and 75 mg groups, respectively, completed 104 weeks. At week 104, ACR20 response rates after multiple imputation in the 300, 150 and 75 mg groups were 69.4, 64.4 and 50.3%, respectively. Sustained clinical improvements were observed through week 104 with secukinumab across other clinically important domains of PsA. Responses were sustained through week 104 regardless of prior anti-TNF-a use. Over the entire treatment period the incidence, type and severity of adverse events were consistent with those reported previously. Conclusion. Secukinumab provided sustained improvements in signs and symptoms and multiple clinical domains in patients of active PsA through 2 years of therapy. Secukinumab was well tolerated, with a safety profile consistent with that reported previously. Trial registration: ClinicalTrials.gov (https://clinicaltrials.gov), NCT0175263

Treatment recommendations for psoriatic arthritis

Objective: To develop comprehensive recommendations for the treatment of the various clinical manifestations of psoriatic arthritis (PsA) based on evidence obtained from a systematic review of the literature and from consensus opinion. Methods: Formal literature reviews of treatment for the most significant discrete clinical manifestations of PsA (skin and nails, peripheral arthritis, axial disease, dactylitis and enthesitis) were performed and published by members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Treatment recommendations were drafted for each of the clinical manifestations by rheumatologists, dermatologists and PsA patients based on the literature reviews and consensus opinion. The level of agreement for the individual treatment recommendations among GRAPPA members was assessed with an online questionnaire. Results: Treatment recommendations were developed for peripheral arthritis, axial disease, psoriasis, nail disease, dactylitis and enthesitis in the setting of PsA. In rotal, 19 recommendations were drafted, and over 80% agreement was obtained on 16 of them. In addition, a grid that factors disease severity into each of the different disease manifestations was developed to help the clinician with treatment decisions for the individual patient from an evidenced-based perspective. Conclusions: Treatment recommendations for the cardinal physical manifestations of PsA were developed based on a literature review and consensus between rheumatologists and dermatologists. In addition, a grid was established to assist in therapeutic reasoning and decision making for individual patients. It is anticipated that periodic updates will take place using this framework as new data become available

Inhibition of interleukin-17 in patients with oligoarticular psoriatic arthritis

Introduction: This study evaluated the efficacy of the interleukin-17A inhibitor secukinumab in patients with oligoarticular psoriatic arthritis (PsA). Methods: A total of 84 patients with oligoarticular PsA, defined as 1–4 tender joints and 1–4 swollen joints, were pooled from the FUTURE 2–5 and MAXIMISE trials (NCT01752634, NCT01989468, NCT02294227, NCT02404350, and NCT02721966). Patients were grouped by treatment received at week 12 (secukinumab 300 mg, secukinumab 150 mg, or placebo) and week 52 (any secukinumab 300 mg or any secukinumab 150 mg). Efficacy was assessed by the proportion of patients achieving selected clinical outcomes. The predictors of Disease Activity index for Psoriatic Arthritis (DAPSA) responses at weeks 12 and 52 were identified by logistic regression analysis. Results: Secukinumab treatment resulted in greater achievement of DAPSA-based low disease activity (LDA), DAPSA-based remission (REM), DAPSA50, and DAPSA75 than placebo at week 12, with improvements sustained or further increased through week 52. LDA or REM was achieved at week 52 by more than 90% of patients who received either secukinumab dose, although secukinumab 300 mg resulted in the highest achievement of the stringent DAPSA75 and DAPSA REM outcomes. At week 12, younger age was associated with DAPSA LDA or REM and DAPSA50, while lower baseline swollen joint count was associated with DAPSA REM. No predictors were identified at week 52. The safety profile was consistent with the full study populations. Conclusion: Secukinumab demonstrated efficacy vs placebo across several outcome measures in patients with oligoarticular PsA at week 12, with sustained or improved responses through week 52

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ABSTRACT. The 2012 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) was held in June 2012 in Stockholm, Sweden, and attended by rheumatologists, dermatologists, and representatives of biopharmaceutical companies and patient groups from around the world. In this Prologue we introduce discussions that were held among meeting attendees. Prior to the 2012 meeting, 2 GRAPPA members organized a Fellows Symposium adjacent to the European Academy of Dermatology and Venerology meeting in Verona, where they discussed comorbidities and treatments of patients with psoriasis. The 2012 GRAPPA meeting began with a trainee symposium, where 30 rheumatology fellows and dermatology residents presented their research work. Other presentations and discussions included a review of arthritis mutilans; dermatology issues including screening tools for psoriatic arthritis (PsA) and the instruments to measure psoriasis severity; cardiovascular and other comorbidities of psoriasis and PsA; development of criteria to define inflammatory arthritis, enthesitis, dactylitis, and spondylitis; distinctions between peripheral spondyloarthritis and PsA; the status of an ultrasound outcome measure for dactylitis; and updates on several GRAPPA projects, including a study of biomarkers to predict structural damage in PsA, the ongoing video project, and several education initiatives

Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Interleukin 17A is a proinflammatory cytokine that is implicated in the pathogenesis of psoriatic arthritis. We assessed the efficacy and safety of subcutaneous secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis. Methods: In this phase 3, double-blind, placebo-controlled study undertaken at 76 centres in Asia, Australia, Canada, Europe, and the USA, adults (aged ≥18 years old) with active psoriatic arthritis were randomly allocated in a 1:1:1:1 ratio with computer-generated blocks to receive subcutaneous placebo or secukinumab 300 mg, 150 mg, or 75 mg once a week from baseline and then every 4 weeks from week 4. Patients and investigators were masked to treatment assignment. The primary endpoint was the proportion of patients achieving at least 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01752634. Findings: Between April 14, and Nov 25, 2013, 397 patients were randomly assigned to receive secukinumab 300 mg (n=100), 150 mg (n=100), 75 mg (n=99), or placebo (n=98). A significantly higher proportion of patients achieved an ACR20 at week 24 with secukinumab 300 mg (54 [54%] patients; odds ratio versus placebo 6·81, 95% CI 3·42–13·56; p<0·0001), 150 mg (51 [51%] patients; 6·52, 3·25–13·08; p<0·0001), and 75 mg (29 [29%] patients; 2·32, 1·14–4·73; p=0·0399) versus placebo (15 [15%] patients). Up to week 16, the most common adverse events were upper respiratory tract infections (four [4%], eight [8%], ten [10%], and seven [7%] with secukinumab 300 mg, 150 mg, 75 mg, and placebo, respectively) and nasopharyngitis (six [6%], four [4%], six [6%], and eight [8%], respectively). Serious adverse events were reported by five (5%), one (1%), and four (4%) patients in the secukinumab 300 mg, 150 mg, and 75 mg groups, respectively, compared with two (2%) in the placebo group. No deaths were reported. Interpretation: Subcutaneous secukinumab 300 mg and 150 mg improved the signs and symptoms of psoriatic arthritis, suggesting that secukinumab is a potential future treatment option for patients with this disorder

Efficacy and safety of secukinumab administration by autoinjector in patients with psoriatic arthritis: results from a randomized, placebo-controlled trial (FUTURE 3)

Background: The study aimed to assess 52-week efficacy and safety of secukinumab self-administration by autoinjector in patients with active psoriatic arthritis (PsA) in the FUTURE 3 study (ClinicalTrials.gov NCT01989468). Methods: Patients (≥ 18 years of age; N = 414) with active PsA were randomized 1:1:1 to subcutaneous (s.c.) secukinumab 300 mg, 150 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and every 4 weeks thereafter. Per clinical response, placebo-treated patients were re-randomized to s.c. secukinumab 300 or 150 mg at week 16 (nonresponders) or week 24 (responders) and stratified at randomization by prior anti-tumor necrosis factor (TNF) therapy (anti-TNF-naïve, 68.1%; intolerant/inadequate response (anti-TNF-IR), 31.9%). The primary endpoint was the proportion of patients achieving at least 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24. Autoinjector usability was evaluated by Self-Injection Assessment Questionnaire (SIAQ). Results: Overall, 92.1% (300 mg), 91.3% (150 mg), and 93.4% (placebo) of patients completed 24 weeks, and 84.9% (300 mg) and 79.7% (150 mg) completed 52 weeks. In the overall population (combined anti-TNF-naïve and anti-TNF-IR), ACR20 response rate at week 24 was significantly higher in secukinumab groups (300 mg, 48.2% (p < 0.0001); 150 mg, 42% (p < 0.0001); placebo, 16.1%) and was sustained through 52 weeks. SIAQ results showed that more than 93% of patients were satisfied/very satisfied with autoinjector usage. Secukinumab was well tolerated with no new or unexpected safety signals reported. Conclusions: Secukinumab provided sustained improvements in signs and symptoms in active PsA patients through 52 weeks. High acceptability of autoinjector was observed. The safety profile was consistent with that reported previously