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Background/Aims Psoriatic nail disease is intimately linked to adjacent distal interphalangeal joint (DIP) disease, and it is important to ascertain whether DIP-nail complex behaves differently under different biological therapies. The aim of this analysis is to assess the effect of ixekizumab (IXE) and adalimumab (ADA) at the individual digit level using the Nail Psoriasis Severity Index (NAPSI) and NAPSI resolution in patients with psoriatic arthritis (PsA) with concomitant nail involvement. Methods This post hoc analysis included patients from SPIRIT-H2H (NCT03151551) treated with either IXE or ADA who had baseline nail disease (NAPSI total score >0) and DIP involvement, with either tenderness or swelling, at the individual digit level for each hand. Nail disease was assessed using the NAPSI scoring system, a measure of nail bed and nail matrix involvement combined for a total maximum score of 80. Proportions of patients having a NAPSI total score >0 were evaluated at baseline, week 24 and week 52; post-baseline assessments were compared between treatment using Fisher’s exact test. Results Of 566 patients in the intent-to-treat SPIRIT-H2H population of, 354 patients (IXE, N = 186; ADA, N = 168) had NAPSI total score >0 and DIP involvement in at least 1 of 10 digits simultaneously at baseline. At week 24, the proportion of patients with nail disease (NAPSI >0) was lower among patients who received IXE versus ADA across all 10 digits and was significantly lower versus ADA for 9 out of the 10 individual digits (p 0 at week 24 between IXE and ADA at the individual digit level was observed, favouring IXE. Similarly, numerically greater improvements were observed with IXE compared to ADA regardless of whether nail bed, nail matrix, or NAPSI total score was assessed. Conclusion These data demonstrate that in patients with PsA with nail involvement, there was a significant advantage of IXE over ADA in resolving nail involvement at the individual digit level as measured by NAPSI. Disclosure D. McGonagle: Consultancies; Eli Lilly and Company, AbbVie. Member of speakers’ bureau; Eli Lilly and Company. Grants/research support; Eli Lilly and Company. Other; BSR attendance support from Eli Lilly and Company. A. Kavanaugh: Consultancies; AbbVie, UCB, Janssen, Novartis, Pfizer. I. McInnes: Consultancies; AbbVie, Amgen, BMS, Causeway Therapeutics, Cabaletta, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, UCB. Grants/research support; AbbVie, Amgen, BMS, Causeway Therapeutics, Cabaletta, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, UCB Pharma. Other; University of Glasgow, Vice Principal & Head of College, NHS Greater Glasgow & Clyde, Non exec board member, Evelo, Board of Directors, Non Exec director, Versus arthritis, Trustee. L. Kristensen: Consultancies; Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly and Company, Janssen. Member of speakers’ bureau; Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly and Company, Janssen. Grants/research support; Pfizer, AbbVie, UCB, Gilead, Biogen, Novartis, Eli Lilly and Company, Janssen. Other; study grant from Novo Nordisk A/S, institutional grant from The Oak Foundation, Cambridge Weight Plan, delivery of dietary supplements. J.F. Merola: Consultancies; Amgen, Bristol-Myers Squibb, AbbVie, Dermavant, Eli Lilly and Company, Novartis, Janssen, UCB, Sanofi, Regeneron, Sun Pharma, Biogen, Pfizer, Leo Pharma. B.E. Strober: Consultancies; AbbVie, Alumis, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Immunic Therapeutics, Bristol-Myers-Squibb, Connect Biopharma, Dermavant, EPI Health, Evelo Biosciences, Janssen, Leo, Eli Lilly and Company, Maruho, Meiji Seika Pharma, Mindera Health, Novartis, Pfizer, UCB Pharma, Sun Pharma, Regeneron, Sanofi-Genzyme, Union Therapeutics, Ventyxbio, vTv Therapeutics. Shareholder/stock ownership; Connect Biopharma, Mindera Health. Honoraria; Editor-in-Chief (honorarium): Journal of Psoriasis and Psoriatic Arthritis. Member of speakers’ bureau; AbbVie, Eli Lilly and Company, Incyte, Janssen, Regeneron, Sanofi-Genzyme. Other; Investigator: Dermavant, Investigator: AbbVie, Investigator: CorEvitas Psoriasis Registry, Investigator: Dermira, Investigator: Cara, Investigator: Novertis. J.R. Lisse: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. J. Pustizzi: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. C. Sapin: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. R. Bolce: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. C. Ritchlin: Consultancies; AbbVie, Janssen, Novartis, BMS, UCB. Member of speakers’ bureau; Pfizer, UCB, AbbVie. Grants/research support; Pfizer, AbbVie.

INTRODUCTION Mirikizumab, an anti-IL23p19 antibody, has demonstrated safety and efficacy versus placebo across clinical remission, symptomatic remission, and endoscopic and histologic endpoints in patients with moderately-to-severely active ulcerative colitis (UC) in a Phase 3, double-blind, 12-week induction study (LUCENT-1/NCT03518086) and 40-week maintenance study (LUCENT-2/NCT03524092). Here, we examine the relationship between bowel urgency (BU) clinically meaningful improvement (CMI) and BU remission with rectal bleeding (RB) remission and stool frequency (SF) remission (Table 1 for definitions). METHODS Patients in LUCENT-1 (N=1281) were randomly assigned 3:1 to receive intravenous mirikizumab 300mg or placebo every four weeks (Q4W) for a total of 12 weeks. Patients who achieved clinical response to mirikizumab by Week 12 of LUCENT-1 (N=544) were re-randomized 2:1 to subcutaneous mirikizumab 200mg or placebo Q4W for 40 weeks in LUCENT-2 (maintenance study). Patients recorded their BU severity in the previous 24 hours using an 11-point Urgency Numeric Rating Scale (UNRS; 0=no urgency to 10=worst possible urgency) in an electronic daily diary. Weekly scores were averaged for patients with at least 4 of 7 days of complete diary data. BU remission was defined as UNRS score of 0 or 1, and BU CMI was defined as ≥3-point decrease in UNRS score compared to baseline. For patients who achieved clinical response at the end of induction, analyses were repeated for the end of maintenance at Week 40 (for 52 weeks of continuous treatment). Patients with UNRS RESULTS A total of 1087 patients reported a baseline UNRS score ≥3. Patients achieving BU CMI had significantly higher rates of RB remission and SF remission at both Week 12 and Week 40 compared with patients not achieving these outcomes (all p CONCLUSION A higher proportion of patients enrolled in LUCENT-1 and -2 who achieved BU CMI and BU remission achieved RB remission and SF remission. These results support that the symptom of bowel urgency is an important marker of UC disease activity that is related to and distinct from other commonly accepted symptoms of active UC.

Introduction In the SPIRIT-H2H (ClinicalTrials.gov: NCT03151551) trial in biologic-naïve patients with active psoriatic arthritis (PsA), ixekizumab (IXE) was superior to adalimumab (ADA) at week 24 in terms of achieving a combined endpoint of ≥ 50% improved response in the American College of Rheumatology scale score (ACR50) and 100% improvement in the Psoriasis Areas and Severity Index (PASI100), and was non-inferior in terms of achieving ACR50. IXE resulted in similar improvements of PsA manifestations irrespective of the use of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), while ADA response was higher with concomitant csDMARD use. The aim of this study was to determine the efficacy and safety of treatment with IXE and ADA with or without methotrexate (MTX), the most commonly use csDMARD, through week 52 in patients with PsA. Methods In the open-label, rater-blinded, head-to-head SPIRIT-H2H trial, randomization of patients was stratified by concomitant use of csDMARD and moderate-to-severe plaque psoriasis involvement. In the post-hoc subgroup analysis presented here, subgroups were defined as with/without concomitant MTX use at baseline. Treatment group effects within subgroups were tested using Fisher’s exact test. Missing data were imputed using non-responder imputation. Results By week 52, IXE provided similar improvements in the combined ACR50 and PASI100 endpoint, ACR50, and other PsA-related domains regardless of whether IXE was used with or without MTX, while ADA efficacy appeared to be improved with concomitant MTX use. When used without concomitant MTX, IXE resulted in significantly higher response versus ADA in terms of the combined ACR50 and PASI100 (p = 0.002) endpoint, minimal disease activity (p = 0.016), and very low disease activity (p = 0.037). The safety of both agents was consistent with their known safety profiles regardless of concomitant MTX use. Conclusion In PsA patients with inadequate control of the disease, IXE delivers consistent efficacy in several clinical domains of the disease regardless of concomitant MTX use. The efficacy of ADA is increased by the concomitant use of MTX. These findings can inform treatment decisions when considering the need for concomitant MTX use with IXE or ADA at initiation or for long-term maintenance. Electronic supplementary material The online version of this article (10.1007/s40744-020-00250-3) contains supplementary material, which is available to authorized users.

ObjectivesSPIRIT head-to-head (H2H) is a 52-week (Wk) trial comparing ixekizumab (IXE) with adalimumab (ADA) for simultaneous American College of Rheumatology (ACR)50 and Psoriasis Area and Severity Index (PASI)100 responses in 566 patients (distributed evenly across both groups) with psoriatic arthritis (PsA). IXE was superior to ADA for this primary end point at Wk24. We aimed to determine the final efficacy and safety results through Wk52 including a prespecified subgroup analysis of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) use.MethodsSPIRIT-H2H is a Wk52 multicentre, open-label, blinded-assessor study comparing IXE and ADA in bionaïve patients with PsA. Patients were randomised 1:1 to IXE or ADA with stratification by concomitant csDMARD use and presence of moderate-to-severe plaque psoriasis. Prespecified end points at Wk24 and Wk52 included musculoskeletal, psoriasis, quality-of life outcomes, subgroup analyses and safety.ResultsA significantly higher proportion of patients treated with IXE versus ADA simultaneously achieved ACR50 and PASI100 (39% vs 26%, pConclusionsIXE provided significantly greater simultaneous joint and skin improvement than ADA through Wk52 in bionaïve patients with PsA. IXE showed better efficacy on psoriasis and performed at least as well as ADA on musculoskeletal manifestations. IXE efficacy was consistent irrespective of concomitant csDMARD use.Trial registration numberNCT03151551.

Background Interleukin-17A (IL-17A) antagonists are a recent innovation for treating psoriatic arthritis (PsA). There are currently no cost-effectiveness analyses (CEAs) comparing the IL-17A antagonists ixekizumab and secukinumab in PsA from a UK perspective. Objective We conducted a CEA from the UK National Health Service perspective to compare ixekizumab versus secukinumab in patients with PsA and concomitant moderate-to-severe plaque psoriasis. Methods A Markov model was developed based on the widely accepted York model. In biologic disease-modifying antirheumatic drug (bDMARD)-naïve patients, ixekizumab → ustekinumab → best supportive care (BSC) was compared with secukinumab → ustekinumab → BSC. For bDMARD-experienced patients, ixekizumab → BSC was compared with secukinumab → BSC. At the end of the bDMARD trial period, Psoriatic Arthritis Response Criteria (PsARC) responders continued to receive the bDMARD in the continuous treatment period. PsARC nonresponders and patients who ceased continuous treatment transitioned to the trial period of the next treatment. Results Ixekizumab was less costly and provided more quality-adjusted life-years (QALYs) than secukinumab in bDMARD-naïve and -experienced patients based on list prices, although cost savings and QALY gains were small to modest. In bDMARD-naïve patients, total costs were £155,455 compared with £155,530 for secukinumab (year 2017 values). Total QALYs were 8.127 versus 7.989. In bDMARD-experienced patients, the corresponding values were £140,051 versus £140,264 for total costs and 3.996 versus 3.875 for total QALYs. Conclusion Ixekizumab provided more QALYs at a marginally lower cost than secukinumab, and the results were most sensitive to changes in drug costs. Other factors, such as patient preferences for the number of injections and confidential price discounts, may be important considerations in clinical decision-making. Electronic supplementary material The online version of this article (10.1007/s41669-020-00202-1) contains supplementary material, which is available to authorized users.

INTRODUCTION: Ixekizumab, a selective interleukin-17A antagonist, was compared with adalimumab in the SPIRIT-H2H study (NCT03151551) in patients with psoriatic arthritis (PsA) and concomitant psoriasis. This post hoc analysis reports outcomes to week 52 in patients from SPIRIT-H2H, stratified by baseline psoriasis severity. METHODS: SPIRIT-H2H was a 52-week, multicenter, randomized, open-label, rater-blinded, parallel-group study of biologic disease-modifying antirheumatic drug (DMARD)-naïve patients (N = 566) with PsA and active psoriasis (≥ 3% body surface area involvement). Patients were randomized to ixekizumab or adalimumab (1:1) with stratification by baseline concomitant use of conventional synthetic DMARDs and psoriasis severity (with/without moderate-to-severe psoriasis). Patients received on-label dosing according to psoriasis severity. The primary endpoint was the proportion of patients simultaneously achieving ≥ 50% improvement in American College of Rheumatology criteria (ACR50) and 100% improvement in Psoriasis Area Severity Index (PASI100) at week 24. Secondary endpoints included musculoskeletal, disease activity (defined by composite indices), skin and nail, quality of life and safety outcomes. In this post hoc analysis, primary and secondary endpoints of SPIRIT-H2H were analyzed by baseline psoriasis severity. RESULTS: A greater proportion of patients achieved the combined endpoint of ACR50 + PASI100 and PASI100 with ixekizumab compared with adalimumab at weeks 24 and 52, regardless of baseline psoriasis severity. ACR response rates were similar for ixekizumab and adalimumab across both patient subgroups. For musculoskeletal outcomes, similar efficacy was seen for ixekizumab and adalimumab, but ixekizumab showed greater responses for skin outcomes regardless of psoriasis severity. The safety profiles of ixekizumab and adalimumab were consistent between subgroups. CONCLUSIONS: Regardless of baseline psoriasis severity, ixekizumab demonstrated greater efficacy than adalimumab with respect to simultaneous achievement of ACR50 + PASI100, and showed consistent and sustained efficacy across PsA-related domains. It also demonstrated higher response rates for skin outcomes. These subgroup analyses highlight the efficacy of ixekizumab in patients with PsA irrespective of the severity of concomitant psoriasis. ispartof: RHEUMATOLOGY AND THERAPY vol:9 issue:1 pages:109-125 ispartof: location:England status: published

Background Nail psoriasis (NP) is common and of high importance in patients with psoriasis. Complete resolution of NP at week 24-26 is an unambiguous nail outcome accessible for indirect treatment comparison of biologics. Objective To evaluate the comparative efficacy of approved biologics in achieving complete resolution of NP at week 24-26. Methods A network meta-analysis (NMA) was conducted to indirectly compare the efficacy of six biologics in achieving complete resolution of NP at week 24-26 in patients with moderate-to-severe psoriasis and concomitant NP. Complete resolution of NP was defined as a score of zero on the Nail Psoriasis Severity Index (NAPSI), modified NAPSI (mNAPSI) or Physician's Global Assessment of Fingernails (PGA-F). Results The probability of achieving complete resolution of NP was highest for ixekizumab (46.5%; 95% credibility interval [CrI] 35.1-58.0; Surface Under the Cumulative RAnking curve [SUCRA] 97%), followed by brodalumab (37.0%; 17.0-61.0; 79%), adalimumab (28.3%; 24.4-32.4; 62%), guselkumab (27.7%; 21.1-35.1; 58%), ustekinumab (20.8%; 10.2-35.2; 37%), and infliximab (0.8%; 0.0-8.9; 17%). Conclusion In patients with moderate-to-severe psoriasis and concomitant NP, ixekizumab has the greatest likelihood among approved biologics of achieving complete resolution of NP at week 24-26. Findings should be interpreted carefully because of inherent study limitations.

Introduction Improvements in both musculoskeletal and non-musculoskeletal manifestations are important treatment goals in psoriatic arthritis (PsA). Objective These post hoc analyses determined whether additional benefits related to various PsA domains are observed in patients simultaneously achieving 50% improvement in American College of Rheumatology criteria (ACR50) and 100% improvement in Psoriasis Area Severity Index (PASI100), the primary endpoint of the SPIRIT-H2H study. Methods Patients with active PsA and psoriasis in SPIRIT-H2H (N = 566) were categorised into two sets of four response groups irrespective of treatment allocation (approved dosages of ixekizumab or adalimumab): patients who simultaneously achieved ACR50 and PASI100 response, achieved ACR50 response only, achieved PASI100 response only, or did not achieve ACR50 or PASI100 response after 24 and 52 weeks of treatment. Patients achieving simultaneous ACR50 and PASI100 response were compared with the other patient response groups at the corresponding time point for efficacy and health-related quality of life (HRQoL) outcomes. Results Patients simultaneously achieving ACR50 and PASI100 responses at week 24 or 52 showed higher rates of ACR70 response, minimal disease activity, Disease Activity in Psoriatic Arthritis ≤ 4, resolution of enthesitis and dactylitis, and HRQoL improvement at weeks 24 and 52, respectively, than the other corresponding response groups at both time points. Conclusion High levels of disease control, such as those obtained with simultaneous achievement of ACR50 and PASI100 response, were linked to better outcomes across a wide range of endpoints that are important for patients with PsA. Patients meeting this combined endpoint showed more comprehensive and thus greater control of disease activity. Trial registration NCT03151551 Key Points• Treatment goals for patients with psoriatic arthritis emphasise the importance of improving both musculoskeletal and non-musculoskeletal manifestations of the disease.• A combined endpoint considering both these manifestations, achievement of at least 50% improvement in American College of Rheumatology criteria and 100% improvement in Psoriasis Area Severity Index, was linked with achievement of a number of other endpoints relevant to psoriatic arthritis, including health-related quality of life that are important to patients with psoriatic arthritis.• Patients meeting the combined endpoint were more likely to achieve a disease state of remission, which is the stated aim of treatment for psoriasis.

Improvements in both musculoskeletal and non-musculoskeletal manifestations are important treatment goals in psoriatic arthritis (PsA).These post hoc analyses determined whether additional benefits related to various PsA domains are observed in patients simultaneously achieving 50% improvement in American College of Rheumatology criteria (ACR50) and 100% improvement in Psoriasis Area Severity Index (PASI100), the primary endpoint of the SPIRIT-H2H study.Patients with active PsA and psoriasis in SPIRIT-H2H (N = 566) were categorised into two sets of four response groups irrespective of treatment allocation (approved dosages of ixekizumab or adalimumab): patients who simultaneously achieved ACR50 and PASI100 response, achieved ACR50 response only, achieved PASI100 response only, or did not achieve ACR50 or PASI100 response after 24 and 52 weeks of treatment. Patients achieving simultaneous ACR50 and PASI100 response were compared with the other patient response groups at the corresponding time point for efficacy and health-related quality of life (HRQoL) outcomes.Patients simultaneously achieving ACR50 and PASI100 responses at week 24 or 52 showed higher rates of ACR70 response, minimal disease activity, Disease Activity in Psoriatic Arthritis ≤ 4, resolution of enthesitis and dactylitis, and HRQoL improvement at weeks 24 and 52, respectively, than the other corresponding response groups at both time points.High levels of disease control, such as those obtained with simultaneous achievement of ACR50 and PASI100 response, were linked to better outcomes across a wide range of endpoints that are important for patients with PsA. Patients meeting this combined endpoint showed more comprehensive and thus greater control of disease activity. Trial registration NCT03151551 Key Points • Treatment goals for patients with psoriatic arthritis emphasise the importance of improving both musculoskeletal and non-musculoskeletal manifestations of the disease. • A combined endpoint considering both these manifestations, achievement of at least 50% improvement in American College of Rheumatology criteria and 100% improvement in Psoriasis Area Severity Index, was linked with achievement of a number of other endpoints relevant to psoriatic arthritis, including health-related quality of life that are important to patients with psoriatic arthritis. • Patients meeting the combined endpoint were more likely to achieve a disease state of remission, which is the stated aim of treatment for psoriasis.

Background Comparisons of PsA treatment options to guide physicians are limited. When conventional treatment is insufficient, the recommendations is a biological agent, most frequently tumour necrosis factor (TNF)-inhibitors. IXE, an IL-17A antagonist biologic, showed superiority over TNF-inhibitor ADA for the simultaneous achievement of ACR50 and PASI100, and PASI100 alone in the SPIRIT-H2H trial at week 24. We analysed differences in efficacy outcomes between IXE and ADA by subgroups based on baseline clinical characteristics. Methods We conducted post-hoc analysis of data from SPIRIT-H2H (NCT03151551), a 52-week, multicentre, open-label, blinded assessor study patients with active PsA (defined as swollen joint count ≥3 and tender joint count ≥3), with a body surface area (BSA) ≥3% and insufficient response to ≥ 1 conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and naïve to biologic (b)-DMARDs. Patients were randomised 1:1 to IXE or ADA, while presence/absence of moderate-to-severe psoriasis (defined as PASI ≥12, static Physician Global Assessment ≥3 and BSA ≥10%) determined on-label dosing. Subgroups were defined by baseline enthesitis, dactylitis, fingernail psoriasis (presence/absence), BSA (6 mg/L). A Fisher’s exact test was used for between group comparisons of efficacy outcome measures at 24 weeks (PASI90, ACR50/70, and minimal disease activity [MDA]). Missing data were overcome by non-responder imputation. Results At week 24, IXE and ADA demonstrated comparable efficacy in ACR50 response rates across all subgroups. ACR70 response in patients with fingernail psoriasis was significantly greater with IXE-treated vs ADA (p = 0.02) (table). PASI90 response with baseline enthesitis (p < 0.001), without dactylitis (p < 0.001), with fingernail psoriasis (p < 0.001), CRP (≤6 mg/L, p = 0.003; >6 mg/L, p = 0.036) and BSA ( Conclusion IXE and ADA are associated with comparable efficacy and associated with a greater effect in certain subgroups. Results will aid clinicians when making treatment choices. Disclosures H. Tahir: Consultancies; Novartis, Eli-Lilly, Abbvie. A.J. Bradley: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. M.H. Nassab: Other; Full time employee of Eli Lilly. B. Möller: None. J.S. Smolen: Consultancies; AbbVie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Medimmune, MSD, Novartis- Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB. Grants/research support; AbbVie, Eli Lilly, Novartis, Pfizer, Roche. C. Sapin: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. C.F. Dionello: Consultancies; Novartis, Lilly, Janssen, Abbvie. Honoraria; Novartis, Lilly, Janssen, Abbvie, Roche, Pfizer. G. Meszaros: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly.

Background With multiple biologic disease-modifying anti-rheumatic drugs (bDMARDs) available, comparisons are important for treatment decisions. At week 24 of the SPIRIT H2H study in patients with active PSA, IXE showed superiority to ADA for the simultaneous achievement of ACR50 and PASI100. Here we report the 52-week efficacy outcomes including individual ACR components and in subgroups +/- concomitant methotrexate (MTX). Methods SPIRIT H2H (NCT03151551) was a 52-week, multicentre, open-label, blinded-assessor study of bDMARD naïve patients with active PSA (defined as swollen joint count ≥3/68, and tender joint count ≥3/66), with a body surface area (BSA) ≥3% and inadequate response to conventional synthetic (cs)-DMARDs. Patients were randomised 1:1 to IXE or ADA stratified by concomitant csDMARD use and the presence of moderate-to-severe psoriasis (defined as Psoriasis Area and Severity Index [PASI] ≥12 combined with a static Physician Global Assessment ≥3 and BSA ≥10%). Patients received approved label dosing of assigned treatment dependent on presence/absence of moderate-to-severe psoriasis. Primary outcome was achievement of simultaneous ACR50 + PASI100; secondary outcomes were achievement of PASI100, ACR20/50/70 and changes in individual ACR component scores. Data were analysed using logistic regression with non-responder imputation for missing data. Results Baseline characteristics were balanced across treatment groups. At week 52, a significantly larger percentage of IXE- vs. ADA-treated patients achieved simultaneous ACR50 + PASI100 and PASI100, consistent with 24-week results (table). IXE performed at least as well as ADA at week 52 for all other outcomes (table). With/without MTX, IXE efficacy was consistent at week 52 across ACR20/50/70 with a significantly greater achievement of simultaneous ACR50 + PASI100 and ACR70 (table). IXE- versus ADA-treatment resulted in comparable changes from baseline for each individual ACR component at week 52. Safety was consistent with previous reports. Conclusion In patients with PSA, treatment with IXE versus ADA resulted in a significantly greater achievement of simultaneous skin and joint improvement at week 52, consistent with week 24 results. At week 52 consistent efficacy was shown for IXE when used with/without MTX. Disclosures C.J. Edwards: Consultancies; Celltrion, Abbvie, Samsung. Honoraria; Abbvie, BMS, Biogen, Chugai, Fresenius, Gilead, Janssen, Lilly, Pfizer, Roche, Samsung, UCB. Member of speakers’ bureau; Abbvie, BMS, Biogen, Chugai, Fresenius, Gilead, Janssen, Lilly, Pfizer, Roche, Samsung, UCB. Grants/research support; Pfizer, Biogen, Abbvie. A.J. Bradley: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. M.H. Nassab: Other; Full time employee of Eli Lilly. B. Möller: None. K.P. Machold: Honoraria; Arsanis, Astro, Baxter, BMS, Celgene, Eli-Lilly, MSD, Pfizer, Roche, Novartis, Sandoz. Member of speakers’ bureau; MSD, Pfizer, BMS, Janssen-Cilag, Sandoz, Novartis, Eli-Lilly. Grants/research support; AbbVie, BMS, Eli-Lilly, Novartis, MSD, Pfizer, Sanofi-Aventis, UCB. C. Sapin: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. R. Ranza: Consultancies; Abbvie, Novartis, Lilly, Pfizer, Janssen. Member of speakers’ bureau; Abbvie, Novartis, Lilly, Pfizer, Janssen. Grants/research support; Abbvie, Novartis, Pfizer, Janssen. S.L. Leage: Other; Full time employee of Eli Lilly.

Background In Europe, IL-17A blocker secukinumab is approved for ankylosing spondylitis (AS). The label dose is 150mg: loading dose regimen at weeks 0, 1, 2, 3 and 4, followed by monthly maintenance dosing. 300mg dose is not indicated for AS. Secukinumab is not yet approved for non-radiographic axial spondyloarthritis (nr-axSpA). Objectives: Describe real-world dose utilization of an IL-17A blocker among axial spondyloarthritis (axSpA) patients with radiographic (AS) and nr-axSpA. Methods Descriptive, cross-sectional survey of physicians managing axSpA (France, Germany, Italy, Spain, UK, Austria & Australia). At the time of survey (April-August 2019), only secukinumab was approved. Physicians completed patient record forms for their next 7 consulting patients currently treated with or discontinued secukinumab, recording demographics, disease activity (Bath Ankylosing Spondylitis Disease Activity Index, BASDAI), Ankylosing Spondylitis Disease Activity Score, ASDAS) and treatment history. Results 275 rheumatologists and 4 orthopedists provided data for 2,101 patients: 1,509 (1151 AS; 358 nr-axSpA) currently receiving secukinumab and 592 (385 AS; 207 nr-axSpA) secukinumab discontinuers. Mean age was 45.1years (45.8 AS; 43.2 nr-axSpA), 64.4% were male (68.8% AS, 52.4% nr-axSpA), and mean time diagnosed was 5.3years (5.9 AS; 3.8 nr-axSpA). 50.5% (48.4% AS; 55.9% nr-axSpA) of patients were receiving secukinumab as their first biologic, 48.4% biologic-experienced. 94.1% (93.9% AS; 94.3% nr-axSpA) of all users were treated beyond loading dose phase of secukinumab; 8.8% dose up-titrated from 150mg to 300mg. Of patients currently receiving secukinumab maintenance, median treatment duration was 44.4weeks (n = 1249). 71.5% (71.4% AS; 72.3% nr-axSpA) received 150mg monthly, 28.5% received a dose outside label (23.7% on 300mg). For discontinuers who reached maintenance phase, median treatment duration was 20.0weeks (n = 547). 38.7% (37.4% AS; 41.3% nr-axSpA) of secukinumab discontinuers received a dose outside label (33.9% on 300mg). 30.5% (28.8% AS; 36.1% nr-axSpA) of biologic-experienced patients received secukinumab 300mg. The utilization of secukinumab 300mg in biologic-experienced discontinuers was 36.9% and higher than in current biologic-experienced users (28.0%). At initiation of secukinumab 150mg, 95.1% and 90.7% of patients had BASDAI≥4 (n = 593) and ASDAS≥2.1 (n = 129), respectively. For those continuing, after a median duration of 42.3weeks, 31.7% (30.4% AS; 35.7% nr-axSpA) had BASDAI≥4 and 30.2% (27.8% AS; 37.5% nr-axSpA) ASDAS≥2.1. At initiation of secukinumab 300mg, 93.1% and 96.4% had BASDAI≥4 (n = 173) and ASDAS≥2.1 (n = 28), respectively. For those continuing, after median duration of 51.9weeks, 42.2% (38.2% AS; 54.8% nr-axSpA) had BASDAI≥4 and 57.1% (52.4% AS; 71.4% nr-axSpA) ASDAS≥2.1. Conclusion In the real-world, secukinumab discontinuation occurred after 20.0weeks, despite approximately one third being treated with secukinumab 300mg. For those remaining on secukinumab, up to 30% used outside-label doses (higher in biologic-experienced patients). Secukinumab is not universally prescribed for the approved indication or at the recommended dose. There is a suggestion that not all patients receiving a higher dose achieve low disease activity. Disclosures N. Booth: Grants/research support; Research was funded by eli-lilly and company. Other; Employed by Adelphi Real World. J. Hill: Other; Employed by Eli Lilly and company. S. Leage: Other; Employed by Eli Lilly and company. C. Sapin: Other; Employed by Eli Lilly and company. E. Holdsworth: Other; Employed by Adelphi Real World. S. Antonelli: Other; Employed by Eli Lilly and company.

Supplemental Digital Content is available in the text., Sexual dysfunction, a common side effect of antipsychotic medications, may be partly caused by dopamine antagonism and elevation of prolactin. In QUALIFY, a randomized study, aripiprazole once-monthly 400 mg (AOM 400), a dopamine D2 receptor partial agonist, showed noninferiority and subsequent superiority versus paliperidone palmitate (PP), a dopamine D2 receptor antagonist, on the Heinrichs–Carpenter Quality-of-Life Scale (QLS) in patients with schizophrenia aged 18–60 years. Sexual dysfunction (Arizona Sexual Experience Scale) and serum prolactin levels were also assessed. Odds for sexual dysfunction were lower with AOM 400 versus PP [week 28 adjusted odds ratio (95% confidence interval), 0.29 (0.14–0.61); P=0.0012] in men [0.33 (0.13–0.86); P=0.023], women [0.14 (0.03–0.62); P=0.0099], and patients aged 18–35 years [0.04 (

Background:Ixekizumab (IXE), a high-affinity monoclonal antibody selectively targeting IL-17A, was superior to adalimumab (ADA) at Week (Wk) 24 for simultaneous achievement of ACR50 and 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI 100) (primary endpoint) in patients (pts) with active PsA from SPIRIT-H2H1. SPIRIT-H2H had two major secondary endpoints and achieved both: noninferiority of IXE to ADA for ACR50 at Wk 24, and superiority of IXE to ADA for PASI 100 at Wk 24.Objectives:To determine how concomitant conventional synthetic DMARD (csDMARD) use affects safety and efficacy of IXE and ADA in prespecified subgroups defined by biologic monotherapy, concomitant MTX use, and concomitant csDMARD use through Wk 52 in SPIRIT-H2H.Methods:SPIRIT-H2H (NCT03151551) was a 52-week, multicentre, randomised, open-label, assessor-blinded, parallel-group study evaluating the efficacy and safety of IXE versus ADA in adults with PsA and naïve to biologic DMARDs. Patients were required to have active PsA fulfilling Classification for Psoriatic Arthritis (CASPAR) criteria and ≥3/68 tender and ≥3/66 swollen joints, ≥3% plaque psoriasis BSA involvement, no prior treatment with bDMARDs, and with prior inadequate response to ≥1 csDMARD (but not necessarily current treatment with csDMARDs). Randomization (1:1) was stratified by concomitant use of csDMARD and the presence/absence of moderate to severe PsO (baseline: BSA≥10% + PASI≥12, + static Physician’s Global Assessment≥3). Patients (N=566) received IXE/ADA through 52 wks according to the labelled dose dependent on presence/absence of moderate-to-severe PsO. In this prespecified subgroup analysis by presence or absence of csDMARDs, efficacy outcomes through wk 52 were compared between IXE and ADA using logistic regression models and Fisher’s exact tests. Missing data were imputed using non-responder imputation.Results:At baseline, 167 of 283 IXE-treated patients and 169 of 283 ADA-treated patients had concomitant MTX use. Of these, 9.0% (15/167) and 7.1% (12/169) treated with IXE and ADA, respectively, were taking an additional csDMARD (sulfasalazine, cyclosporine, or leflunomide). A significantly greater proportion of patients on IXE versus ADA achieved the primary endpoint or PASI 100 when used as monotherapy or in combination with csDMARD (Figure 1A and 1C). At Wk 52, the proportion of patients achieving ACR50 was not statistically different between IXE and ADA, regardless of monotherapy or concomitant csDMARD use (Figure 1B). A significantly higher proportion of patients achieved MDA on IXE compared to ADA in the monotherapy subgroup (49% vs 33%), while the response rates were similar in both combination subgroups (Figure 1D). These data support consistent ACR50, PASI 100, and MDA response for IXE across all three subgroups. Frequencies of adverse events were similar across the three subgroups for IXE and ADA (Figure 2).Conclusion:As with prior studies,2,3consistent efficacy across multiple PsA disease-specific endpoints was observed with IXE in SPIRIT-H2H, regardless of whether IXE was taken as monotherapy or in combination with MTX or another csDMARD. No unexpected safety signals were found for either agent.References:[1]Mease et al, Ann Rheum Dis 2020;79:123-31.[2]Coates et al, RMD Open 2017;3:e000567.[3]Nash et al, RMD Open 2018;4:e000692.Disclosure of Interests:Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Anthony Sebba Consultant of: Genentech, Gilead, Lilly, Regeneron Pharmaceuticals Inc., Sanofi, Speakers bureau: Lilly, Roche, Sanofi, Eric Ruderman Consultant of: Pfizer, Amanda Gellett Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Christophe Sapin Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Aubrey Trevelin Sprabery Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Soyi Liu Leage Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Sreekumar Pillai Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Paulo Reis Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB

Author(s): Potkin, Steven G; Loze, Jean-Yves; Forray, Carlos; Baker, Ross A; Sapin, Christophe; Peters-Strickland, Timothy; Beillat, Maud; Nylander, Anna-Greta; Hertel, Peter; Nitschky Schmidt, Simon; Eramo, Anna; Hansen, Karina; Naber, Dieter | Abstract: BackgroundQUALIFY was a 28-week, randomized, open-label, head-to-head trial that assessed improvements across multiple measures in stable patients with schizophrenia with aripiprazole once-monthly 400 mg vs paliperidone palmitate.MethodsSecondary effectiveness assessments included physician-rated readiness for work using the Work Readiness Questionnaire, the Clinical Global Impression-Severity and Clinical Global Impression-Improvement scales, and quality of life with the rater-blinded Heinrichs-Carpenter Quality of Life Scale. Patients assessed their treatment satisfaction and quality of life with Subjective Well-Being under Neuroleptic Treatment-short version and Tolerability and Quality of Life questionnaires.ResultsOdds of being ready for work at week 28 were significantly higher with aripiprazole once-monthly 400 mg vs paliperidone palmitate (adjusted odds ratio, 2.67; 95% CI, 1.39-5.14; P=.003). Aripiprazole once-monthly 400 mg produced numerically or significantly greater improvements from baseline vs paliperidone palmitate in all Quality of Life Scale items. With aripiprazole once-monthly 400 mg vs paliperidone palmitate at week 28, there were significantly more Clinical Global Impression-Severity and Clinical Global Impression-Improvement responders (adjusted odds ratio, 2.26; P=.010, and 2.51; P=.0032) and significantly better Clinical Global Impression-Improvement scores (least squares mean treatment difference, -0.326; 95% CI, -0.60 to -0.05; P=.020). Numerically larger improvements with aripiprazole once-monthly 400 mg vs paliperidone palmitate were observed for patient-rated scales Subjective Well-Being under Neuroleptic Treatment-short version and Tolerability and Quality of Life. Partial correlations were strongest among clinician-rated and among patient-rated scales but poorest between clinician and patient-rated scales.ConclusionsConsistently greater improvements were observed with aripiprazole once-monthly 400 mg vs paliperidone palmitate across all measures. Partial correlations between scales demonstrate the multidimensionality of various measures of improvement. More patients on aripiprazole once-monthly 400 mg were deemed ready to work by the study end.Trial registryNational Institutes of Health registry, NCT01795547, https://clinicaltrials.gov/ct2/results?id=NCT01795547).

Background Prescription rates for long-acting injectable (LAI) antipsychotic formulations remain relatively low in Europe despite improved adherence over alternative oral antipsychotic treatments. This apparent under-prescription of LAI antipsychotics may have multiple contributing factors, including negative mental health practitioner attitudes towards the use of LAIs. Methods The Antipsychotic Long acTing injection in schizOphrenia (ALTO) non-interventional study (NIS), conducted across several European countries, utilised a questionnaire that was specifically designed to address physicians’ attitudes and beliefs towards the treatment of schizophrenia with LAI antipsychotics. Exploratory principal component analysis (PCA) of feedback from the questionnaire aimed to identify and characterize the factors that best explained the physicians’ attitudes towards prescription of LAIs. Results Overall, 136/234 solicited physicians returned fully completed questionnaires. Physicians’ mean age was 48.5 years, with mean psychiatric experience of 20.0 years; 69.9% were male, 84.6% held a consultant position, and 91.9% had a clinical specialty in general adult care. Most physicians considered themselves to have a high level of clinical experience with LAI antipsychotics (77.2%), with an increased rate of LAI antipsychotics prescription over the last 5 years (59.6%). Although the majority of physicians (69.9%) declared feeling no difference in stress levels when offering LAI compared to oral antipsychotics, feelings of ‘no/more stress’ versus ‘less stress’ was found to influence prescription patterns. PCA identified six factors which collectively explained 66.1% of the variance in physician feedback. Multivariate analysis identified a positive correlation between physicians willing to accept usage of LAI antipsychotics and the positive attitude of colleagues (co-efficient 3.67; p = 0.016). Conclusions The physician questionnaire in the ALTO study is the first to evaluate the attitudes around LAI antipsychotics across several European countries, on a larger scale. Findings from this study offer an important insight into how physician attitudes can influence the acceptance and usage of LAI antipsychotics to treat patients with schizophrenia.

Schizophrenia presents a substantial clinical and economic burden to the health-care system. In QUAlity of LIfe with AbiliFY Maintena (QUALIFY), a randomized head-to-head study of aripiprazole once-monthly 400 mg (AOM 400) compared with paliperidone palmitate (PP; 78–234 mg/mo), AOM 400 demonstrated greater improvement in health-related quality of life and functioning in patients with stable schizophrenia. The present analysis used health economics assessment data collected during the QUALIFY study to determine the direct medical and pharmacy costs and the cost-effectiveness associated with each treatment over 6 months. Compared with those receiving PP, patients receiving AOM 400 incurred significantly lower direct total costs ($8908±186 vs $9675±190, p=0.005) and treatment costs ($7967±113 vs $8706±116, p

ObjectiveTo conduct a cost-effectiveness analysis from the perspective of the Spanish National Health System (NHS) comparing ixekizumab versus secukinumab.DesignA Markov model with a lifetime horizon and monthly cycles was developed based on the York model. Four health states were included: a biological disease-modifying antirheumatic drug (bDMARD) induction period of 12 or 16 weeks, maintenance therapy, best supportive care (BSC) and death. Treatment response was assessed based on both Psoriatic Arthritis Response Criteria (PsARC) and ≥90% improvement in the Psoriasis Area Severity Index score (PASI90). At the end of the induction period, responders transitioned to maintenance therapy. Non-responders and patients who discontinued maintenance therapy transitioned to BSC. Clinical efficacy data were derived from a network meta-analysis. Health utilities were generated by applying a regression analysis to Psoriasis Area Severity Index and Health Assessment Questionnaire‒Disability Index scores collected in the ixekizumab SPIRIT studies. Results were subject to extensive sensitivity and scenario analysis.SettingSpanish NHS.ParticipantsA hypothetical cohort of bDMARD-naïve patients with psoriatic arthritis and concomitant moderate-to-severe psoriasis was modelled.InterventionsIxekizumab and secukinumab.ResultsIxekizumab performed favourably over secukinumab in the base-case analysis, although cost savings and quality-adjusted life-year (QALY) gains were modest. Total costs were €153 901 compared with €156 559 for secukinumab (difference −€2658). Total QALYs were 9.175 vs 9.082 (difference 0.093). Base-case results were most sensitive to the annual bDMARD discontinuation rate and the modification of PsARC and PASI90 response to ixekizumab or secukinumab.ConclusionIxekizumab provided more QALYs at a lower cost than secukinumab, with differences being on a relatively small scale. Sensitivity analysis showed that base-case results were generally robust to changes in most input parameters.Trial registration numberSPIRIT-P1: NCT01695239; Post-results, SPIRIT-P2: NCT02349295; Post-results.

Background:Ixekizumab (IXE) was shown to be superior to adalimumab (ADA) in achievement of simultaneous improvement of joint and skin disease (ACR50 and PASI100) in patients with active psoriatic arthritis (PsA) and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).1Objectives:To compare the safety and tolerability profile of IXE vs ADA in patients with PsA up to 52 weeks of treatment.Methods:SPIRIT-H2H (NCT03151551) was an open-label, head-to-head, blinded assessor clinical trial which included patients with active PsA (≥3 tender joint count + ≥3 swollen joint count) and plaque psoriasis (BSA ≥3%) who were inadequate responders to csDMARD therapy but naïve to biologic DMARDs. Patients were randomized (1:1) to approved dosing of IXE or ADA. Safety events were assessed at each patient visit up to Week 52. Frequencies of adverse events (AEs) were based on the number of patients in the safety population (patients who received ≥1 dose of study drug). Cases of inflammatory bowel disease (IBD) and cerebro-cardiovascular events were adjudicated by external committees. Kaplan-Meier analysis of time to onset of serious adverse events (SAEs) was performed.Results:Of the 283 patients randomized to each treatment, 87% (246/283) of patients who received IXE and 84% (237/283) of patients who received ADA completed 52 weeks of treatment. The frequency of treatment-emergent AEs (TEAEs) was similar between the groups (74% IXE vs 69% ADA), however fewer severe TEAEs were reported in the IXE group (3.2% IXE vs 7.1% ADA) (Table). SAEs were significantly more frequent in the ADA group compared to the IXE group (12% vs 4.2%; pConclusion:Safety results were consistent with previous trials with IXE and ADA. Compared with IXE, patients with PsA treated with ADA had significantly more serious AEs.References:[1]Mease PJ, et al.Ann Rheum Dis.2020;79(1):123-31.Table.Safety results at 52 weeksIXE N=283n (%)ADA N=283n (%)TEAEs209 (74)194 (69) Severea9 (3.2)20 (7.1) Related to study treatmentb98 (35)87 (31)Serious adverse events12 (4.2)35 (12)***Deaths00Discontinuation due to AE12 (4.2)21 (7.4)Serious infections3 (1.1)4 (1.4)Injection-site reactionsc30 (11)10 (3.5)** Severe01 (0.4) Resulted in discontinuation2 (0.7)3 (1.1)Anaphylaxis00Inflammatory bowel disease2 (0.7)0 Ulcerative colitis1 (0.4)d0 Crohn’s disease1 (0.4)0Cerebro-cardiovascular events5 (1.8)7 (2.5) MACE02 (0.7)Malignancies04 (1.4)Depression5 (1.8)9 (3.2)Interstitial lung disease01 (0.4)Cytopenias9 (3.2)12 (4.2)Hepatic events18 (6.4)20 (7.1)aPatients with multiple occurrences of the same event are counted under the highest severity.bThe TEAE’s relationship to study treatment was judged by the investigator.cMedDRA high-level term.dThis event was adjudicated but it was not a confirmed IBD. ***pDisclosure of Interests:Philip J Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Eli Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer, Sun Pharma, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer, UCB Pharma, Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Arthur Kavanaugh Grant/research support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB – grant/research support, Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Gaia Gallo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Soyi Liu Leage Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Christophe Sapin Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme

Background:Psoriatic Arthritis (PsA) treatment should aim to achieve robust improvement of arthritis as well as control of extra-articular manifestations like the skin. SPIRIT-H2H evaluated the efficacy of ixekizumab (IXE) and adalimumab (ADA) in patients with active PsA and psoriasis, and naïve to biologic Disease-Modifying Anti-Rheumatic Drugs (bDMARDs). At week 24 (W24), IXE showed superiority to ADA in simultaneous achievement of ACR50 and PASI100 as well as significant improvement of treat-to-target and other extra-articular outcomes.Objectives:To examine and to compare PsA efficacy outcomes in patients beyond achievement of the primary endpoint of the SPIRIT-H2H trial at W24, irrespective of treatment allocation.Methods:All patients recruited had active PsA (defined as tender joint count ≥3/68, swollen joint count ≥3/66 and body surface area [BSA] ≥3%), and inadequate response to conventional synthetic (cs)-DMARDs. Patients were randomised 1:1 to open-label, assessor-blinded IXE or ADA. We conducted post-hoc analysis of SPIRIT-H2H (NCT03151551), categorizing patients into four independent groups based on the achievement of the primary outcome (ACR50 & PASI100), ACR50 only, PASI100 only or none of them after 24 weeks of treatment. Statistical analyses consisted of mixed model for repeated measurement and logistic regression models using non-response imputation.Results:At week 24, patients reaching simultaneously ACR50 and PASI100 had a statistically significant higher response in most treat-to-target endpoints than those meeting ACR50 only (pTable.Efficacy Endpoints at W24ACR50 & PASI100ACR50 onlyPASI100 onlyNeither ACR50 nor PASI100n=181n=94n=121n=170ACR20100.0b,c100.053.734.7ACR7064.6a,b,c48.90.00.0MDA75.7a,b,c60.623.112.4VLDA32.6a,b,c13.83.31.8DAPSA LDA or Remission (≤14)92.3a,b,c81.943.028.8DAPSA Remission (≤4)44.8b,c35.16.62.4HAQ-DI score ≤0.575.7b,c64.930.627.4PASI75100.0a,c60.6100.037.1PASI90100.0a,c36.2100.014.7SF-36 PCS change from baseline§12.3±0.53b,c12.3±0.745.4±0.664.0±0.55Data are presented as %;§mean±standard error.apbpcpACR, American College of Rheumatology; DAPSA, Disease Activity in Psoriatic Arthritis; HAQ-DI, Health Assessment Questionnaire Disability Index; LDA, Low Disease Activity; MDA, Minimal Disease Activity; PASI, Psoriasis Area Severity Index; VLDA, Very Low Disease Activity.Nine patients with active PsO and BSA≥3% were assessed as PASI=0 at baseline, a medical inconsistency that was resolved using medical judgement. These patients were considered PASI100 responders if PASI=0 and BSA=0 at post baseline visits.Conclusion:Reflecting the complexity of PsA, different degrees of improvement were observed across all treat-to-target outcomes with greater improvements in patients that met ACR50 response regardless of skin resolution. These findings at week 24 need to be confirmed with a longer duration of treatment.Disclosure of Interests:Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Frank Behrens Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Lilly and Roche, Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai, Soyi Liu Leage Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Christophe Sapin Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Inmaculada De La Torre Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Gabriella Meszaros Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Andrew Ostor Consultant of: MSD, Pfizer, Lilly, Abbvie, Novartis, Roche, Gilead and BMS, Speakers bureau: MSD, Pfizer, Lilly, Abbvie, Novartis, Roche, Gilead and BMS, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB

Background:Psoriatic arthritis (PsA) is a chronic systemic disease with manifestations affecting musculoskeletal and extra-articular domains. Treatment and assessment of response are therefore major challenges in routine clinical practice. Minimal disease activity (MDA) is a multidimensional endpoint that can define a treatment target1. In SPIRIT-H2H2, a head-to-head clinical trial comparing the efficacy and safety of ixekizumab (IXE) versus) to adalimumab (ADA), the percentage of patients simultaneously achieving American College of Rheumatology 50 (ACR50) and Psoriasis Area and Severity Index 100 (PASI100), was the primary endpoint in order to reflect improvement in two domains of PsA.Objectives:To evaluate how individual components of the simultaneous achievement of ACR50 and PASI100 compare with those of MDA at week 24.Methods:Patients with active PsA (defined as those with a tender joint count [TJC] ≥ 3/68, a swollen joint count [SJC] ≥ 3/66 and a body surface area [BSA] of active plaque psoriasis ≥ 3%) were randomised 1:1 to approved dosing (according to baseline psoriasis involvement) of IXE or ADA in SPIRIT-H2H, an open label, assessor-blinded study.The proportion of patients meeting each criterion of the composite endpoints was calculated for the intent-to-treat ([ITT], N=566) population and the population of MDA responders at Week 24 (N=235). Missing individual responses were imputed with non-responder status. Spidergrams were generated using SAS 9.4.Results:For both the overall ITT population and the MDA responders population, the use of PASI≤1 or BSA≤3% in the skin-related component of the MDA contributed to the higher response rate relative to the PASI100 response. Thus, the PASI100 response is a more stringent endpoint. Proportions of responders are similar across MDA and ACR50+PASI100 individual components for HAQ and SJC. The high baseline TJC levels (mean TJC: IXE=19.1, ADA=21.3) as opposed to lower levels observed for baseline SJC (mean SJC: IXE=10.1, ADA=10.7) made MDA-TJC criterion (≤1) more difficult to achieve than the equivalent criterion of the ACR50+PASI100 endpoint.Conclusion:Despite the differences in criteria definitions, there are consistent response patterns in the individual components of the simultaneous ACR50+PASI100 and MDA endpoints in particular for the peripheral arthritis domain.References:[1]Smolen, Josef S et al. “Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force.”Annals of the rheumatic diseasesvol. 77,1 (2018): 3-17.[2]Mease PJ The SPIRIT H2H study group, et al. “A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial.”Annals of the Rheumatic Diseases2020;79:123-131.Disclosure of Interests:Laura C Coates: None declared, Michael Nissen Grant/research support from: Abbvie, Consultant of: Novartis, Lilly, Abbvie, Celgene and Pfizer, Speakers bureau: Novartis, Lilly, Abbvie, Celgene and Pfizer, Celine El Baou Consultant of: Eli Lilly and Company, Jane Zochling Employee of: Jannssen Cilag, Speakers bureau: Janssen Cilag, AbbVie, Novartis, UCB, BMS, Eli Lilly, Antonio Marchesoni Speakers bureau: Abbvie, Pfizer, UCB, Novartis, Celgene, Eli Lilly, Soyi Liu Leage Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Enrique Soriano Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer Inc, Sandoz, Consultant of: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer Inc, Sandoz, Speakers bureau: AbbVie, Amber, Bristol-Myers Squibb, Eli Lilly, Novartis, Pfizer Inc, Roche, Valderilio F Azevedo Grant/research support from: Abbvie, Janssen, Bristol-Myers Squibb, Boehringer-Ingelheim, Lilly and Novartis, Consultant of: Lilly, Novartis, Janssen, Boehringer-Ingelheim, Amgen, Pfizer and Abbvie, Speakers bureau: Sandoz, Celltrion, Lilly, Novartis, Janssen, Boehringer-Ingelheim, Amgen, Pfizer and Abbvie, Klaus Machold Grant/research support from: AbbVie, MSD, UCB, Consultant of: Arsanis, Astro, Baxter, BMS, Celgene, Eli-Lilly, MSD, Pfizer, Roche, Novartis, Sandoz, Speakers bureau: MSD, Pfizer, BMS, Janssen-Cilag, Sandoz, Novartis, Eli-Lilly, Christophe Sapin Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company

BackgroundBiologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs are used in patients with psoriatic arthritis (PsA), but few studies directly compare their clinical efficacy. In such situations, network meta-analysis (NMA) can inform evidence-based decision-making.ObjectiveTo evaluate the comparative efficacy and safety of approved bDMARDs in patients with PsA.MethodsBayesian NMA was conducted to compare the clinical efficacy of bDMARDs at weeks 12‒16 in bDMARD-naïve patients with PsA in terms of American College of Rheumatology (ACR) criteria, Psoriatic Arthritis Response Criteria (PsARC) and Psoriasis Area and Severity Index (PASI). Safety end points were evaluated in the overall mixed population of bDMARD-naive and bDMARD-experienced patients.ResultsFor ACR, all treatments except abatacept were statistically superior to placebo. Infliximab was most effective, followed by golimumab and etanercept, which were statistically superior to most other treatments. Ixekizumab 80 mg every 2 weeks (Q2W) was statistically superior to abatacept subcutaneous, apremilast and both regimens of ustekinumab; similar findings were observed for ixekizumab 80 mg Q4W. For PsARC response, ixekizumab did not significantly differ from other therapies, except for golimumab, infliximab and etanercept, which were superior to most other agents including ixekizumab. For PASI response, infliximab was numerically most effective, but was not statistically superior to ixekizumab, which was the next best performing agent. Analysis of safety end points identified few differences between treatments.ConclusionOur NMA confirms the efficacy and acceptable safety profile of bDMARDs in patients with active PsA. There were generally few statistically significant differences between most treatments.

Myrlene S Aigbogun,1 Sizhu Liu,2 Siddhesh A Kamat,1 Christophe Sapin,3 Amy M Duhig,2 Leslie Citrome4 1Health Economics and Outcomes Research, Otsuka Pharmaceutical Development and Commercialization, Inc, Princeton, NJ, USA; 2Global Health Economics and Outcomes Research, Xcenda, Palm Harbor, FL, USA; 3Global Analytics, Lundbeck, Paris, France; 4Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, NY, USA Objective: This study used a decision-analytic framework to assess the cost-effectiveness of brexpiprazole vs comparator branded therapies for reducing relapses and hospitalizations among adults with schizophrenia from a US payer perspective.Methods: An economic model was developed to assess patients with stable schizophrenia initiating treatment with brexpiprazole (1–4 mg), cariprazine (1–6 mg), or lurasidone (40–80 mg) over a 1-year period. After 6 months, patients remained on treatment or discontinued due to relapse, adverse events, or other reasons. Patients who discontinued due to relapse or adverse events were assumed to have switched to other therapy, and those who discontinued due to other reasons were assumed to have received no therapy. Primary outcomes were incremental cost per relapse avoided and hospitalization avoided, and the secondary outcome was cost per quality-adjusted life-year (QALY) gained. Sensitivity and scenario analyses were also conducted.Results: Brexpiprazole was associated with the highest per-patient clinical effectiveness (avoided relapses 0.637, avoided hospitalizations 0.719, QALYs 0.707) among comparators, followed by cariprazine (avoided relapses 0.590, avoided hospitalizations 0.683, QALYs 0.683) and lurasidone (avoided relapses 0.400, avoided hospitalizations 0.536, QALYs 0.623). Annual per-patient health-care costs were lowest for brexpiprazole ($20,510), followed by cariprazine ($22,282) and lurasidone ($25,510). Brexpiprazole was the least costly and most effective treatment strategy for all outcomes. Results were sensitive to relapse rates and daily cost of brexpiprazole. Limitations include data principally obtained from drug-specific randomized withdrawal studies and lack of direct-comparison trials.Conclusion: This analysis evaluated brexpiprazole treatment for the reduction of schizophrenia relapses and hospitalizations over a 1-year period compared to other recently available branded antipsychotics, and excluded generic antipsychotic treatments. Brexpiprazole treatment may lead to clinical benefits and medical cost savings, and provides a cost-effective treatment option for patients relatively to other branded second-generation antipsychotics. Keywords: schizophrenia, cost-effectiveness, relapse prevention, cost-benefit, indirect analysis, event avoided, hospitalization avoided, brexpiprazole

Background:The Antipsychotic Long-acTing injection in schizOphrenia (ALTO) study was a non-interventional study across several European countries examining prescription of long-acting injectable (LAI) antipsychotics to identify sociodemographic and clinical characteristics of patients receiving and physicians prescribing LAIs. ALTO was also the first large-scale study in Europe to report on the use of both first- or second-generation antipsychotic (FGA- or SGA-) LAIs.Methods:Patients with schizophrenia receiving a FGA- or SGA-LAI were enrolled between June 2013 and July 2014 and categorized as incident or prevalent users. Assessments included measures of disease severity, functioning, insight, well-being, attitudes towards antipsychotics, and quality of life.Results:For the 572 patients, disease severity was generally mild-to-moderate and the majority were unemployed and/or socially withdrawn. 331/572 were prevalent LAI antipsychotic users; of whom 209 were prescribed FGA-LAI. Paliperidone was the most commonly prescribed SGA-LAI (56% of incident users, 21% of prevalent users). 337/572 (58.9%) were considered at risk of non-adherence. Prevalent LAI users had a tendency towards better insight levels (PANSS G12 item). Incident FGA-LAI users had more severe disease, poorer global functioning, lower quality of life, higher rates of non-adherence, and were more likely to have physician-reported lack of insight.Conclusions:These results indicate a lower pattern of FGA-LAI usage, reserved by prescribers for seemingly more difficult-to-treat patients and those least likely to adhere to oral medication.

Background Psoriatic arthritis (PsA) is a chronic inflammatory rheumatic disease associated with psoriasis and characterised by pain, stiffness, swelling of joints, joints ankylosing and low patient quality of life.1 The economic burden of PsA is substantial2, and biologic treatments for PsA are increasingly scrutinised in health technology assessments. The most commonly used economic model framework for assessing biologics in PsA is the York Assessment Group model developed as part of a NICE appraisal (the “York model”).3 In this model improvement in Health Assessment Questionnaire- Disability Index (HAQ-DI) reflects physical function, and is linked to initial treatment response measured by joint improvement assessed by PsARC. Objectives To assess the effectiveness of biologic DMARDs on HAQ-DI among active biologic-naive PsA patients through Bayesian network meta-analyses (NMAs) and to understand the relationship to PsARC response. Methods Data for the NMA was identified through a systematic literature review of published and grey literature (1990-May 2017) in EMBASE/MEDLINE. Bayesian NMAs were conducted in line with NICE guidelines4 to assess the mean HAQ-DI scores change from baseline for ixekizumab, adalimumab, ustekinumab, etanercept, golimumab, infliximab, apremilast, secukinumab, certolizumab pegol, and placebo in the biologic-naive overall population as well as in PsARC responders and non-responders. Results were expressed as absolute mean change from baseline and associated standard deviations, and 95% credibility intervals. Results Overall, 42 publications reporting 19 randomised clinical trials were included for the NMAs, most of these evaluated outcomes at 12 and 24 weeks. Mean changes in HAQ-DI score (overall and by PsARC response) from baseline are shown in figure 1. Among PsARC responders, the greatest mean changes were observed for infliximab, etanercept, ixekizumab, and secukinumab. Among PsARC non-responders, those values were greatest for infliximab, etanercept, ixekizumab Q2W, secukinumab, and adalimumab. The relatively wide 95% credibility intervals reflect the scarcity of available evidence. Conclusions The results of the NMAs suggest that among the biologic DMARDs infliximab, etanercept, ixekizumab Q2W, secukinumab 150 mg, and certolizumab had the highest HAQ-DI improvements in biologic-naive patients with active PsA. Changes in HAQ-DI were strongly associated with PsARC response for each treatment. References [1] Lee S, et al. P T. Dec 2010;35(12):680–689. [2] Kawalec P, et al. Expert Rev Pharmacoecon Outcomes Res2015Feb;15(1):125–132. [3] 3. Woolacott N, et al. Health Technol Assess 2006 Sep;10(31):iii-iv, xiii-xvi, 1–239. [4] Dias SWN, et al. Nice DSU technical support document 2: A generalised linear modelling framework for pairwise and network meta-analysis of randomised controlled trials2011. Disclosure of Interest A. Ruyssen-Witrand: None declared, C. Sapin Employee of: Eli Lilly and Company, S. Hartz Employee of: Eli Lilly and Company, S. Liu Leage Employee of: Eli Lilly and Company

Objective To directly compare aripiprazole once-monthly 400 mg (AOM 400) and paliperidone palmitate once-monthly (PP) on the Heinrichs–Carpenter Quality-of-Life Scale (QLS), a validated health-related quality of life and functioning measure in schizophrenia. Method This 28-week, randomized, non-inferiority, open-label, rater-blinded, head-to-head study (QUALIFY) of AOM 400 and PP in adult patients (18–60 years) comprised oral conversion, initiation of AOM 400 or PP treatment, and continuation with intramuscular injections every 4 weeks. The primary endpoint assessed non-inferiority and superiority on QLS total score analyzed using a mixed model for repeated measurements. Results Of 295 randomized patients, 100/148 (67.6%) of AOM 400 and 83/147 (56.5%) of PP patients completed 28 weeks of treatment. A statistically significant least squares mean difference in change from baseline to week 28 on QLS total score (4.67 [95%CI: 0.32;9.02], p = 0.036) confirmed non-inferiority and established superiority of AOM 400 vs PP. There were also significant improvements in Clinical Global Impression — Severity scale and the Investigator's Assessment Questionnaire for AOM 400 vs PP, and pre-defined sub-group analyses revealed a consistent pattern of significance favoring AOM 400 in patients ≤ 35 years. Common treatment-emergent adverse events in the treatment continuation phase were more frequent with PP vs AOM 400, and adverse events were the most frequent reason for discontinuation (27/137 [19.7%] for PP and 16/144 [11.1%] for AOM 400). All-cause discontinuation was numerically lower with AOM 400. Conclusion Superior improvements on clinician-rated health-related quality of life and a favorable tolerability profile suggest greater overall effectiveness for aripiprazole once-monthly vs paliperidone palmitate. ClinicalTrials.gov identifier: NCT01795547 .

To determine the Minimal Clinically Important Difference (MCID) of the Heinrichs-Carpenter Quality of Life Scale (QLS). Data from the "Schizophrenia Trial of Aripiprazole" (STAR) study were used in this analysis. The MCID value of the QLS total score was estimated using the anchor-based method. These findings were substantiated/validated by comparing the MCID estimate to other measurements collected in the study. Half of the patients (49%) showed improvement in Clinical Global Impressions of Severity (CGI-S) during the trial. The estimated MCID of the QLS total score was 5.30 (standard error: 2.60; 95% confidence interval: [0.16; 10.43]; p < 0.05). Patients were divided into two groups: "QLS improvers" (QLS total score increased ≥ six points) and "non-improvers". The QLS improvers had significantly better effectiveness and reported significantly higher levels of preference for their current medications. There was a statistically significant difference between the two groups in the change in two of the four domains of QLS; "Interpersonal relations" and "Intrapsychic foundations" domains during the study. These findings support the value of the estimated MCID for the QLS and may be a useful tool in evaluating antipsychotic treatment effects and improving long-term patient outcomes in schizophrenia. Copyright © 2015 John Wiley & Sons, Ltd.

Objective To evaluate long-term safety and effectiveness of continued treatment with aripiprazole once-monthly 400 mg (AOM 400) in patients with schizophrenia. Methods Patients who completed the QUALIFY study ( NCT01795547 ) in the AOM 400 arm were eligible for 6 additional once-monthly injections of AOM 400 during an open-label, 24-week extension ( NCT01959035 ). Safety data were collected at each visit. Effectiveness measures included change from baseline in health-related qualify of life and functioning on the Heinrichs-Carpenter Quality of Life scale (QLS) and Clinical Global Impression – Severity (CGI-S) scale. Results Of the 88 patients enrolled, 77 (88%) completed the extension study. Most common treatment-emergent adverse events (incidence ≥ 2%) were weight increased (6/88, 7%), toothache (3/88, 3%) and headache (3/88, 3%). Effectiveness was maintained during the extension study, with small but continued improvements from baseline: the least squares mean (LSM) change (95% CI) from baseline to week 24 was 2.32 (− 1.21 to 5.85) for the QLS total score and − 0.10 (− 0.26 to 0.06) for the CGI-S score. The aggregated LSM change (95% CI) from baseline of the lead-in study to week 24 of the extension study was 11.54 (7.45 to 15.64) for the QLS total score and − 0.98 (− 1.18 to − 0.79) for the CGI-S score. Conclusions AOM 400 was well tolerated in patients continuing AOM treatment during the extension phase of the QUALIFY study. Robust and clinically meaningful improvements in health-related quality of life and functioning were maintained, further supporting the long-term clinical benefits of AOM 400 for the treatment of patients with schizophrenia.

Quality of life (QoL) assessments illustrate the patients’ subjective views and needs and can play a key role in drug development of treatments for schizophrenia. So far, QoL data from trials with antipsychotics are mainly used for commercial and promotional purposes or for negotiations on pricing and reimbursement. In the future, a greater focus on QoL could change the development process and guide research for the next generation of treatments, since these will have to significantly improve outcomes and not simply reduce symptoms or re-hospitalization rates. The chapter identifies important aspects of methodology with regard to the selection and use of QoL assessments in drug development. So far, there are no universally accepted operational definition of QoL and no “gold standard” instrument. Based on a variety of theoretical constructs that cover general and disease-specific aspects of health-related quality of life (HRQL), there is a suitable choice of assessment tools with adequate psychometric properties. Cautious selection according to the specific aims of a trial and a sensible integration into clinical programs can help uncover crucial properties of treatments that are vital for reaching ambitious goals like recovery from the illness. However, besides treatment, QoL assessments are also influenced by illness-related and other factors, which need to be considered judiciously to draw valid conclusions from trials. It is now evident that a vast majority of patients with schizophrenia can provide relevant information on HRQL. Regulatory authorities have declared their willingness to review claims based on QoL data and are providing guidance documents to sponsors for this purpose, which can also apply to schizophrenia.

Atypical antipsychotics have similar clinical efficacy in the treatment of schizophrenia; variability in their tolerability represents the discerning factor in treatment choices. Sertindole has a relatively good tolerability profile that favours long-term patient adherence and, therefore, is associated with lower rates of relapse and rehospitalization.A model was developed to compare the cost-effectiveness of a 5-year treatment strategy starting with sertindole versus olanzapine, risperidone, aripiprazole or the typical antipsychotic agent, haloperidol.The model was based on published trials and local clinical practice, and considered costs from the perspective of the Swedish National Health Insurance Board.All atypical agents were clinically superior and more cost-effective than haloperidol with a cost per quality-adjusted life year gained of approximately 490,000 Swedish kroner. Sertindole was associated with the lowest direct and indirect medical costs, driven by its tolerability profile.Sertindole represents a useful alternative to the current treatment options available in Sweden.The relatively good tolerability profile of sertindole translates into lower costs of schizophrenia management, primarily driven by substantially lower direct and indirect costs. Sertindole appears to be a clinically and cost-effective alternative in the management of patients with schizophrenia in Sweden.

Schizophrenia is a severe and debilitating psychiatric disorder. Pharmacological interventions aim to ameliorate symptoms and reduce the risk of relapse and costly hospitalisation. Despite the established efficacy of antipsychotic medication, compliance to treatment is poor, particularly with oral formulation. The emergence of long acting injectable (LAI) antipsychotic formulations in recent years has aimed to counteract the poor compliance rates observed and optimise long term patient outcomes.To estimate the cost-effectiveness of aripiprazole once-monthly 400mg (AOM 400) vs. risperidone long acting injectable (RLAI), paliperidone long acting injectable (PLAI) and olanzapine long acting injectable (OLAI) in the maintenance treatment of chronic, stable schizophrenia patients in the United Kingdom.A Markov model was developed to emulate the treatment pathway of a hypothetical cohort of patients initiating maintenance treatment with LAI antipsychotics. The economic analysis was conducted from a National Health Service (NHS) and Personal Social Services (PSS) perspective over a 10 year time horizon. Efficacy and safety probabilities were derived from mixed treatment comparisons (MTCs) where possible. Analyses were conducted assuming pooled dosing from randomised clinical trials included in the MTCs.The model estimates that AOM 400 improves clinical outcomes by reducing relapses per patient comparative to other LAIs over the model time horizon (2.38, 2.53, 2.70, and 2.67 for AOM 400, RLAI, PLAI and OLAI respectively). In the deterministic analysis, AOM 400 dominated PLAI and OLAI; an incremental cost-effectiveness ratio (ICER) of GBP 3,686 per QALY gained was observed against RLAI. Results from the univariate sensitivity analyses highlighted the probability and cost of relapse as main drivers for cost-effectiveness. In the probabilistic sensitivity analysis, AOM 400 demonstrated a marginally higher probability of being cost-effective (51%) than RLAI, PLAI and OLAI (48%, 1% and 0%, respectively) at a willingness to pay threshold of GBP 20,000.The model was built to accommodate results of an adjusted MTC analysis. Furthermore the model effectively captures repercussions of deteriorating compliance to treatment by incorporating three levels of compliance with elevated risks of relapse for partial compliance and non-compliance. Limitations of the analysis include the limited number of studies incorporated in the MTC, the extrapolation of short term clinical data and the exclusion of the wider societal burden.Comparative to other atypical antipsychotics, AOM 400 represents value for money in the maintenance treatment of chronic, stable schizophrenia; however, in light of the PSA findings and comparable cost-effectiveness (i.e. against RLAI), the product profile and wider benefits of the respective treatments must be taken into account when prescribing antipsychotics.Future research should assess the use of LAI antipsychotics earlier in the disease course of schizophrenia to see whether improved compliance and outcomes shortly following the onset of psychosis has the potential to alter the disease trajectory. Moreover it should be assessed whether changes in the disease trajectory can alleviate cost and resource pressures placed on national health services.

Objective. Escitalopram is a new selective serotonin reuptake inhibitor indicated for the treatment of major depressive disorder (MDD). The objective of this study is to examine its efficacy in the treatment of severe MDD compared with that of citalopram in daily practice. Method. A prospective, naturalistic, 8-week study was conducted involving 127 patients fulfilling DSM-IV criteria for severe MDD and having a baseline Montgomery-Asberg Depression Rating Scale (MADRS) score of at least 30. A full non-parsimonious logistic model, called the propensity score, was first defined to reduce bias associated with non-randomization. The primary efficacy analysis was the mean change from baseline to week 8 in MADRS score between the escitalopram and citalopram groups, after stratification on the propensity score. Other efficacy measurements consisted of the Clinical Global Impression of Severity and Improvement scales (CGI-S and CGI-I, respectively), response (defined as a reduction of at least 50% on MADRS from baseline to week 8) and remission rates (defined as MADRS ≤ 12 at week 8), after adjustment on propensity score for escitalopram use. Results. A total of 67 escitalopram-treated patients and 60 citalopram-treated patients were enrolled in this study. Escitalopram reduced mean MADRS total score at week 8 compared with citalopram (-23.5 vs. -17.5; P

Background Satisfaction is considered a valuable measure of outcome of healthcare processes. Only a few anesthesia-related validated questionnaires are reported. Because their scope is restricted to specific clinical contexts, their use remains limited. The objective of the current study was to develop and validate a self-reported questionnaire, Evaluation du Vecu de l'Anesthesie Generale (EVAN-G), assessing the satisfaction of the perioperative period surrounding general anesthesia. Methods Development of the EVAN-G questionnaire comprised a phase of item generation and a phase of psychometric validation. The patient sample was generated to be proportionally matched to the population of patients undergoing general anesthesia in France. The structure of the questionnaire was identified studying interitem, item-dimension, and interdimension correlations and factor analyses. Data were concurrently gathered to assess external validity. The discriminant validity was determined by comparison of scores across well known patient groups. Reliability was assessed by computation of Cronbach alpha coefficients and by test-retest. Results Eight hundred seventy-four patients were recruited in eight anesthesia departments. The EVAN-G includes 26 items; six specific scores and one global index score are available. Correlations between EVAN-G scores and other concurrent measures supported convergent validity. The EVAN-G correlated poorly with age, American Society of Anesthesiologists physical status, total anesthesia time, and number of previous anesthesias. Significantly higher satisfaction was reported by patients older than 65 yr, belonging to the laryngeal mask group. Reliability and reproducibility were shown. Conclusion The EVAN-G adds important information oriented toward patients' perceptions. The authors' approach provides a novel, valid, and reliable tool that may be used in anesthesia practice.