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Background Secukinumab has demonstrated sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) over 2 years in the FUTURE 2 study (NCT01752634). This post hoc analysis assessed the ability of secukinumab to achieve Psoriatic Arthritis Disease Activity Score (PASDAS)-based remission or low disease activity (LDA) through 2 years among patients with PsA in the FUTURE 2 study. Methods PASDAS (cut-off scores: remission ≤ 1.9; LDA > 1.9 and < 3.2; Moderate Disease Activity ≥ 3.2 and < 5.4; and high disease activity [HDA] ≥ 5.4) was assessed in the overall population (tumour necrosis factor inhibitor [TNFi]-naïve and TNFi-experienced), in patients stratified by prior TNFi use and by disease duration at weeks 16, 52 and 104. The impact of secukinumab on individual PASDAS core components and on the relationship between PASDAS states and patient-reported outcomes (PROs), including physical function, health-related quality of life (HRQoL) and work productivity, were also assessed. Data for the approved doses of secukinumab (300 and 150 mg) are reported. PASDAS scores and core components were reported as observed, and PROs were analysed using mixed models for repeated measures. Results In the overall population, PASDAS remission and LDA were achieved in 15.6% and 22.9%, respectively, of patients treated with secukinumab 300 mg and in 15.2% and 19.2%, respectively, in the secukinumab 150 mg group versus 2.3% and 13.8%, respectively, with placebo at week 16. In the TNFi-naïve group, a higher proportion of patients achieved remission + LDA at week 16 with secukinumab 300 and 150 mg (46.2% and 42.9%, respectively) versus placebo (17.5%), with corresponding responses in TNFi-experienced patients being 22.6% and 19.4% versus 13.3%. Remission/LDA responses with secukinumab were sustained through 2 years. Patients achieving remission/LDA reported greater improvements in PROs than patients in HDA through 2 years. Conclusions Secukinumab-treated patients achieved higher PASDAS-defined remissions or LDA compared with placebo at week 16, which were sustained through 2 years. Remission/LDA was achieved by both TNFi-naïve and TNFi-experienced patients treated with secukinumab, with higher rates in TNFi-naïve patients. Secukinumab-treated patients achieving remission/LDA reported significantly greater improvements in PROs, including physical function and different dimensions of health-related quality of life and work, than patients in HDA. Trial registration ClinicalTrials.gov, NCT01752634 . Registered on December 19, 2012. EUDRACT, 2012-004439-22 . Registered on December 12, 2012.

Background Symptoms and comorbidities of ankylosing spondylitis (AS) considerably reduce health-related quality of life (HRQoL) and ability to work. This real-world study assessed rates of tumour necrosis factor inhibitor (TNFi) use and switching, treatment failure, and associations between failing TNFi and HRQoL, work productivity and activity impairment (WPAI). Methods AS patients and their treating physicians completed questionnaires capturing patient demographics, clinical status, TNFi treatment history, reasons for switching TNFi, HRQoL and WPAI. Current TNFi was determined as “failing” if, after ≥3 months, physician-rated disease severity had worsened, remained severe, was “unstable/deteriorating”, physicians were dissatisfied with disease control and/or did not consider treatment a “success”. Results The analysis included 2866 AS patients from 18 countries. Of 2795 patients with complete treatment data, 916 (32.8%) patients had never received TNFi therapy, 1623 (58.1%) patients were receiving their 1st TNFi and 200 (7.2%) patients had ever received ≥2 TNFi (treatment switch). Primary or secondary lack of efficacy were the commonest reasons for switching, and the mean delay in switching after primary lack of efficacy was 11.1 months. 232 (15.4%) patients on TNFi were currently “failing” who, compared to those with treatment success, reported poorer HRQoL: 5-dimension EuroQoL (EQ-5D-3 L): 0.63 vs. 0.78; Medical Outcomes Study Short-Form Health Survey version 2 (SF-36v2) mental component summary (MCS): 41.8 vs. 46.3; physical component summary (PCS): 40.2 vs. 45.1; impaired work productivity: 46.4% vs. 25.0%; and activity: 44.5% vs. 29.6%; all P  < 0.001. Conclusions Among AS patients, switching TNFi is uncommon and delayed by nearly 1 year despite primary lack of efficacy. Patients currently failing TNFi experience worse physical function, HRQoL and work productivity.

ObjectiveThere are limited data on therapy selection and switching in psoriatic arthritis (PsA). This 18 country, real-world study assessed use and switching of immunomodulatory therapy (biologic/apremilast), the extent of treatment failure and its association with reduced physical functioning, health-related quality of life (HRQoL), and work productivity and activity impairment (WPAI).MethodsPsA patients under routine care and their treating physicians provided demographics, current therapy, reasons for switching, duration of first therapy, HRQoL, HAQ-DI, and WPAI. Current immunomodulatory therapy was determined as “failing” if, after ≥ 3 months, physician-rated disease severity had worsened, remained severe, was “unstable/deteriorating,” or they were dissatisfied with disease control and/or did not consider treatment a “success.”ResultsIncluded were 3714 PsA patients; 1455 (40.6%) had never received immunomodulatory therapy; 1796 (50.1%) had ever received 1 immunomodulatory therapy and 331 (9.2%) ≥ 1. Lack of efficacy with first immunomodulatory therapy was the most common reason for switching; patients whose physicians indicated “primary lack of efficacy” as the reason, switched after a mean of 9.4 months. Patients currently failing immunomodulator therapies (n = 246) had poorer HRQoL compared with treatment success (n = 1472) measured by EQ-5D-3L (0.60 vs 0.77%; P < 0.0001); SF-36 PCS (40.8% vs 46.1%; P < 0.0001) MCS (41.1% vs 45.3%; P < 0.0001). Physical functioning, activity, and work productivity were also more impaired (HAQ-DI: 0.88 vs 0.56; activity impairment: 46.7% vs 29.7%; overall work impairment: 35.4% vs 26.1%; all P < 0.0001).ConclusionsPoor treatment response in PsA is associated with substantial negative patient impact. In cases of primary treatment failure, timely switching is needed.

Secukinumab, a fully human monoclonal IgG1 antibody that selectively neutralizes the proinflammatory cytokine IL-17A, has been approved in Europe in 2015 for the treatment of adult patients with moderate-to-severe plaque psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis (AS). This analysis assessed the budget impact of introduction of secukinumab to the Italian market for all three indications from the perspective of the Italian National Health Service. A cross-indication budget impact model was developed and included biologic-treated adult patients diagnosed with psoriasis, PsA, and AS. The analyses were conducted over a 3-year time horizon and included direct costs (drug therapy costs, administration costs, diseases-related costs, and adverse events costs). Model input parameters (epidemiology, market share projections, resource use, and costs) were obtained from the published literature and other Italian sources. The robustness of the results was tested via one-way sensitivity analyses: secukinumab cost, secukinumab market share, intravenous administration costs, and adverse events costs were varied by ±10%. The total patient population for secukinumab over the 3-year timeframe was projected to be 6,648 in the first year, increasing to 12,001 in the third year, for all three indications combined (psoriasis, PsA, and AS). Compared to a scenario without secukinumab in the market, the introduction of secukinumab in the market for the treatment of psoriasis, PsA, and AS showed a cumulative 3-year incremental budget impact of -5%, corresponding to savings of €66.1 million and per patient savings of about €1,855. The majority of the cost savings came from the adoption of secukinumab in AS (58%), followed by PsA (29%) and psoriasis (13%). Sensitivity analyses confirmed the robustness of the results. Results from this cross-indication budget impact model show that secukinumab is a cost-saving option for the treatment of PsA, AS, and psoriasis patients in Italy.

Background Pain is one of the most important domains affecting health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). Secukinumab has demonstrated rapid and sustained improvements in signs and symptoms, including HRQoL, among patients with active PsA. This analysis evaluates the effect of secukinumab on patient-reported pain in PsA through 104 weeks of treatment. Methods Pain was assessed through week 104 using clinically relevant measures, including change from baseline in a pain visual analog scale (VAS) and Short Form-36 (SF-36) bodily domain scores; proportion of patients reporting improvements equal to or better than minimum clinically meaningful differences in the pain VAS and SF-36 bodily pain domain scores; and proportion of patients with no, moderate, or extreme pain/discomfort measured by the EuroQoL 5-Dimension 3-Level Questionnaire (EQ-5D-3 L) pain item scores. Correlations of pain measures were analyzed using Pearson’s correlation coefficient. Pre-specified analyses of TNF-naïve patients and patients who stopped TNF-inhibitors (TNFis) due to inadequate responses or safety/tolerability (TNF-IR patients) were performed using “as-observed data.” Results Mean improvements from baseline in pain VAS scores were greater with secukinumab versus placebo by week 3 (− 16.9; P  < 0.0001 with secukinumab 300 mg and − 12.6; P  < 0.05 with secukinumab 150 mg) and sustained through week 104. SF-36 bodily pain domain scores were significantly greater with 300 mg secukinumab and secukinumab 150 mg versus placebo by week 4 (16.2 and 16.3, respectively; P  < 0.0001 for both), and these changes were maintained through week 104. With both secukinumab 300 mg and secukinumab 150 mg, improvements equal to or better than the minimum clinically meaningful differences in pain VAS and SF-36 bodily pain were significant versus placebo at week 3 and week 4, respectively. At week 4, 15%, 9%, and 5% of patients receiving secukinumab 300 mg, secukinumab 150 mg, and placebo, respectively, reported “no pain/discomfort” measured by EQ-5D-3 L; these proportions increased to week 104 with both secukinumab doses. Similarly, improvements in pain measures were significant in both TNF-naïve and TNF-IR patients. Conclusion Secukinumab provided rapid and sustained pain relief in PsA over 2 years of treatment. Improvements in pain were reported regardless of prior exposure to TNFis. Trial registration ClinicalTrials.gov, NCT01752634 . Registered on 19 December 2012.

Background/ObjectiveThe incidence of pain and/or fatigue in people with psoriatic arthritis (PsA) is associated with reduced health-related quality of life (HRQoL) and the ability to work, despite modern advanced therapeutic approaches. This real-world, international study examined these relationships in patients with PsA treated with tumour necrosis factor inhibitors (TNFi).MethodsData from 13 countries were analysed. Patients with PsA and their physicians completed questionnaires capturing demographics, current therapy, current disease status, HRQoL and work status via Medical Outcomes Study 36-Item Short-Form version 2 (SF-36v2), 3-level 5-dimension EuroQoL questionnaire, Health Assessment Questionnaire Disability Index, and Work Productivity and Activity Impairment (WPAI) questionnaire.Results640 patients with PsA were included who had been receiving TNFi for ≥3 months and had completed SF-36v2 bodily pain and vitality domains. Of these, 33.1%, 29.2% and 37.7% of patients reported no, moderate and severe pain, respectively, and 31.9%, 22.5% and 45.6% of patients reported low, moderate and severe fatigue, respectively. Scores across HRQoL variables and WPAI were significantly different across pain and fatigue cohorts (all p<0.0001), with HRQoL and WPAI measures considerably worse in patients with moderate to severe pain or fatigue than those with low pain or fatigue.ConclusionsDespite treatment with biologic agents such as TNFi, data from this global study demonstrated that substantial pain and/or fatigue persist in patients with PsA and that these are significantly associated with reduced HRQoL, physical function and work productivity. These findings suggest that there is an unmet need for additional PsA therapies.

To compare healthcare resource utilization and costs between ankylosing spondylitis (AS) patients and a matched sample from the general population without AS covered by the German Statutory Health Insurance (SHI) system, a non-interventional retrospectively matched cohort analysis was conducted using anonymized SHI claims data. Data from January 1st, 2011 through December 31st, 2014 were analyzed. Individuals with a coded diagnosis of AS during the enrollment period comprising the full year of 2013 were directly matched (1:5) to individuals without AS diagnosis in the whole study period by age, gender, hospitalizations, and comorbidities. All-cause healthcare resource utilization and direct costs were analyzed for the year 2013. Statistical tests were applied to compare the differences between the two sampled populations. In 2013, 10,208 AS patients were identified and matched to a sample of 51,040 patients without AS from the general population. Healthcare resource utilization was significantly higher in all healthcare sectors (inpatient, outpatient, pharmaceuticals, remedies, devices and aids, and sick leave) in the AS cohort. Mean all-cause healthcare costs per patient were about €2475 higher in the AS cohort compared to the general population. Most important cost drivers were hospitalizations and pharmaceuticals in terms of bDMARDs prescribed in 10% of the patients. Real-world data from this German claims database analysis showed that AS is associated with a substantial incremental economic burden to the healthcare system.

IntroductionSecukinumab 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.MethodsIndividual 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).ResultsAfter 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).ConclusionsIn 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.FundingNovartis Pharma AG.

BackgroundFatigue is an important symptom associated with active psoriatic arthritis (PsA) and can impact on health-related quality of life (HRQoL) and social functioning. Secukinumab (SEC) has resulted in rapid improvements in signs and symptoms, physical functioning and HRQoL in patients with active PsA vs placebo (PBO) in the FUTURE 1 (F1) and FUTURE 2 (F2) studies. Rapid improvements in fatigue were reported in F2.ObjectivesTo assess 1- and 2-year data on the effects of SEC on fatigue in patients with PsA, including both biologic-naïve patients and those with an inadequate response to TNF therapy (TNF-IR) and to investigate correlations between fatigue and baseline characteristics or clinical endpoints.MethodsPatients with active PsA (F1, N=606; F2, N=397) received SEC or PBO every 4 weeks. Patients receiving PBO who did not meet predefined response criteria at week 16 were re-randomized at week 24 to active treatment. Fatigue was assessed at baseline and weeks 4, 8, 12, 16, 24, 52 and 104 using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. A change in FACIT-F score of ≥4 from baseline was used to define fatigue response. Logistic regression was used to explore the relationship between fatigue response (weeks 16 and 52) and baseline characteristics and clinical response criteria. The FACIT-F response analyses were based on observed data with no imputation; the FACIT-F score analyses used mixed-effect model repeated measure imputation.ResultsImprovements in fatigue compared with PBO were observed for all SEC doses in from week 4 onwards. A fatigue response at week 16 was achieved by 58.4% (F1) and 70.0% (F2) of patients receiving SEC 150 mg, compared with 51.6% (F1) and 43.2% (F2) of those receiving PBO (see figure for F1 data). For SEC 300 mg, a 16 week response was achieved by 50.5% (F2). Responses were sustained at week 52 for 150 mg (F1, 67.2%; F2, 68.5%) and 300 mg (F2, 60.2%) and at week 104 for 150 mg (F1, 63.8%). Sustained responses were also seen in both biologic-naïve (F1, n=425; F2, n=258) and TNF-IR patients (F1, n=181; F2, n=104). Logistic regression analyses of pooled data from F1 and F2 found age and baseline HAQ-DI scores were associated with fatigue response (weeks 16 and 52). Achieving a fatigue response was moderately to strongly correlated with clinical response criteria (including ACR, HAQ-DI and PASI scores at weeks 16 and 52).ConclusionsSEC provided rapid and sustained improvements in fatigue for up to 104 weeks in patients with active PsA, regardless of prior biologic exposure. Achieving a fatigue response was moderately to strongly correlated with improvement in clinical response criteria, indicating a relationship between fatigue and PsA disease activity. SEC-induced sustained improvements in fatigue may be important for improving HRQoL in patients with PsA. Analysis of factors predictive of fatigue response may help to clarify the drivers of fatigue; this study highlights the importance of age and physical functioning.Disclosure of InterestL. Gossec Consultant for: Abbvie, Celgene, Janssen, Novartis, Pfizer, Roche and UCB, T. K. Kvien Grant/research support from: AbbVie, BMS, MSD, Pfizer, Roche and UCB, Consultant for: AbbVie, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Novartis, Orion Pharma, Pfizer, Roche, Sandoz and UCB, P. Conaghan Speakers bureau: Abbvie, Janssen, Lilly, Novartis, Pfizer, Roche, M. Østergaard Grant/research support from: Abbvie, BMS, Janssen, Merck, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB, and Wyeth, J. Cañete Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Biogen, Janssen, Merck, Novartis, Pfizer and UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Biogen, Janssen, Merck, Novartis, Pfizer and UCB, C. Gaillez Shareholder of: Novartis, Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis, E. Davenport Consultant for: Novartis, S. Jugl Shareholder of: Novartis, Employee of: Novartis

BackgroundPatients with active ankylosing spondylitis (AS) experience fatigue which frequently leads to reduced health-related quality of life (HRQoL). Secukinumab (SEC) treatment results in rapid improvements in signs and symptoms, physical functioning and HRQoL in patients with active AS versus placebo (PBO) in the phase 3 studies MEASURE 1 (M1) and MEASURE 2 (M2).ObjectivesTo assess the impact of SEC on fatigue in patients with AS, including biologic-naïve patients and those with an inadequate response to TNF therapy (TNF-IR) and to investigate correlations between fatigue and baseline characteristics or clinical endpoints.MethodsThe two phase 3 studies involved patients with active AS (M1, N=371; M2, N=219). Patients were randomized to receive subcutaneous SEC 150 mg or 75 mg or PBO administered every 4 weeks after initiating therapy. Patients randomized to PBO who did not meet predefined response criteria at week 16 were re-randomized at week 24 to SEC 150 mg or 75 mg. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. The FACIT-F response analyses were based on observed data with no imputation. A change in FACIT-F score of ≥4 from baseline was used to define fatigue response. Possible correlations between baseline characteristics or clinical response criteria and improvements in fatigue at weeks 16 and 52 were investigated using a logistical regression model.ResultsFrom week 4 onwards, greater improvements in fatigue response were observed for both SEC groups compared with PBO. At week 16, 66.4% (M1) and 77.6% (M2) of patients receiving SEC 150 mg achieved a fatigue response, compared with 47.7% (M1) and 50.0% (M2) for PBO (p <0.05 for both comparisons; see figure). Response rates for SEC 150 mg at week 16 were numerically higher in biologic-naïve patients (M1, n=271; M2, n=134) than in TNF-IR patients (M1: 68.9% vs 59.4%; M2: 86.0% vs 62.5%, respectively). Responses were sustained at week 52 in both studies (M1, 73.6%; M2, 80.6%) and at week 104 in M1 (71.3%; see figure for M1 data) in the overall population, and in the two subgroups according to prior biologic therapy status. Correlation analyses based on pooled data from both studies did not identify any baseline factors that consistently predicted an improvement or worsening of FACIT-F score at week 16 or 52. Achieving a fatigue response was strongly positively correlated at weeks 16 and 52 with clinical response (ASAS20, 40, 5/6 responses, ASAS partial remission, ASDAS-CRP major improvement and BASDAI 50 response).ConclusionsSEC 150 mg provided rapid improvement in fatigue, regardless of prior biologic therapy, and response was sustained up to 104 weeks. Fatigue response showed a strong correlation with improvement in clinical response criteria, indicating a relationship between fatigue and disease activity in AS and is an important treatment goal for patients with AS.Disclosure of InterestT. K. Kvien Grant/research support from: AbbVie, BMS, MSD, Pfizer, Roche and UCB, Consultant for: AbbVie, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Novartis, Orion Pharma, Pfizer, Roche, Sandoz and UCB, P. Conaghan Speakers bureau: Abbvie, Janssen, Lilly, Novartis, Pfizer and Roche, A. Deodhar Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Janssen, Novartis, Pfizer and UCB, Consultant for: AbbVie, Amgen, Boehringer Ingelheim, Janssen, Novartis, Pfizer and UCB, L. Gossec Consultant for: Abbvie, Celgene, Janssen, Novartis, Pfizer, Roche and UCB, M. Østergaard Grant/research support from: Abbvie, BMS, Janssen, Merck, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB, and Wyeth., J. Cañete Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Biogen, Janssen, Merck, Novartis, Pfizer and UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Biogen, Janssen, Merck, Novartis, Pfizer and UCB, K. Gandhi Shareholder of: Novartis, Employee of: Novartis, H. Richards Shareholder of: Novartis, Employee of: Novartis, N. Williams Consultant for: Novartis, S. Jugl Shareholder of: Novartis, Employee of: Novartis