INTERVENTION: Trade Name: Taltz Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed INN: IXEKIZUMAB Other descriptive name: LY2439821 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 80‐ Trade Name: Humira Product Name: Humira Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed INN: ADALIMUMAB CAS Number: 331731‐18‐1 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 40‐ CONDITION: Psoriatic Arthritis ; MedDRA version: 20.0 Level: LLT Classification code 10037160 Term: Psoriatic arthritis System Organ Class: 100000004859 Therapeutic area: Diseases [C] ‐ Musculoskeletal Diseases [C05] PRIMARY OUTCOME: Main Objective: To assess whether ixekizumab; is superior to adalimumab at; Week 24 in the treatment of; patients with active PsA as; measured by American College of Rheumatology 50 (ACR50); and Psoriasis Area and Severity; Index 100 (PASI 100) Primary end point(s): Proportion of Participants Simultaneously Achieving American College of Rheumatology (ACR)50 and Psoriasis Area and Severity Index (PASI)100 ; Secondary Objective: To assess whether ixekizumab is noninferior to adalimumab at; Week 24 in the treatment of patients with active PsA as; measured by ACR50; ; To assess whether ixekizumab; is superior to adalimumab at; Week 24 in the treatment of; patients with active PsA as; measured by PASI 100; ; To assess the effect of treatment with ixekizumab compared with adalimumab over 52 weeks as measured by various efficacy and quality of life outcomes Timepoint(s) of evaluation of this end point: Week 24 INCLUSION CRITERIA: Presents with established diagnosis of active psoriatic arthritis for at least 6 months, and currently meets Classification for Psoriatic Arthritis (CASPAR) criteria Active psoriatic arthritis (PsA) defined as the presence of at least 3 tender and at least 3 swollen joints Presence of active plaque psoriasis Men must agree to use a reliable method of birth control or remain abstinent during the study Women must agree to use reliable birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 495 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55 SECONDARY OUTCOME: Secondary end point(s): Proportion of Participants Achieving ACR50 ; ; Proportion of Participants Achieving PASI100 ; ; Change from Baseline in Tender Joint Count (TJC) ; ; Change from Baseline in Swollen Joint Count (SJC) ; ; Change from Baseline in Participant's Assessment of Pain VAS ; ; Change from Baseline in Participant's Global Assessment of Disease Activity ; ; Change from Baseline in Physician's Global Assessment of Disease Activity ; ; Change from Baseline in C‐Reactive Protein (CRP) ; ; Change from Baseline in Health Assessment Questionnaire‐Disability Index (HAQ‐DI) ; ; Proportion of Participants Simultaneously Achieving ACR50 and PASI100 ; ; Change from Baseline in Disease Activity Score‐CRP (DAS28‐CRP) ; ; Proportion of Participants Achieving Minimal Disease Activity (MDA) ; ; Proportion of Participants Achieving Psoriatic Arthritis Response Criteria (PsARC) ; ; Change from Baseline in Modified Composite Psoriatic Disease Activity Index (CPDAI) Score (Modified) ; ; Change from Baseline in the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index in Participants with Enthesitis at Baseline ; ; Change from Baseline in the Leeds Enthesitis Index (LEI) in Participants with Enthesitis at Baseline ; ; Change from Baseline in the Leeds Dactylitis Index‐Basic (LDI‐B) in Participants with Dactylitis at Baseline ; ; Change from Baseline in Psoriasis Body Surface Area (BSA) ; ; Change from Baseline in the Nail Psoriasis Severity Index (NAPSI) Fingernails Score in the Subgroup of Participants with Fingernail Involvement at Baseline ; ; Change from Baseline in the Itch NRS; ; Change from Baseline in Fatigue Severity NRS (Fatigue NRS) Score ; ; Change From Baseline in Medical Outcomes Study 36‐item Short Form Health Survey (SF‐36): Physical Component Summary (PCS) and Mental Component Summary (MCS) ; ; Change from Baseline in Measures of Health Utility (EuroQol‐5 Dimensions 5 Level [EQ‐5D 5L]) ; ; Change from Baseline in Dermatology Life Quality Index (DLQI) Total Score; ; Change from Baseline on the Treatment Satisfaction Questionnaire ; ; Change from Baseline in Columbia Suicide Severity Rating Scale (C‐SSRS) Timepoint(s) of evaluation of this end point: Week 24 and 52
Registro de estudios»Clinical Trials Registry - India
Año»2017
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INTERVENTION: Intervention1: Ixekizumab: Ixekizumab ‐ 80 mg subcutaneous (SC)injection: A starting dose of ixekizumab 160 mg (two 80‐mg SC injections) will be administered at randomization (Visit 2 [Week 0]) for all patients ï?· Patients with moderate‐to‐severe plaque psoriasis (Ps), defined as PASI â?¥12, static Physicianâ??s Global Assessment (sPGA) â?¥3, and BSA â?¥10%, will receive ixekizumab 80 mg given as 1SC injection every 2 weeks (Q2W) from Week 2 to Week 12 and every 4 weeks (Q4W) thereafter ï?· Patients not meeting criteria for moderate‐to‐severe plaque Ps at randomization will receive ixekizumab 80 mg given as 1 SC injection Q4W starting at Week 4 Control Intervention1: Adalimumab: Adalimumab 40 mg SC injection: Patients with moderate‐to‐severe plaque Ps, defined as PASI â?¥12, sPGA â?¥3, and BSA â?¥10%, will receive a starting dose of adalimumab 80 mg (two 40‐mg SC injections) administered at randomization (Visit 2 [Week 0]) followed by 40 mg given as 1 SC injection Q2W starting at Week 1 ï?· Patients not meeting criteria for moderate‐to‐severe plaque Ps will receive a starting dose of adalimumab 40 mg given as 1 SC injection at randomization (Visit 2 [Week 0]) followed by 40 mg given as 1 SC injection Q2W starting at Week 2 CONDITION: Patients with Psoriatic Arthritis PRIMARY OUTCOME: To assess whether ixekizumab ; is superior to adalimumab at ; Week 24 in the treatment of ; patients with active PsA as ; measured by American College ; of Rheumatology 50 (ACR50) ; and Psoriasis Area and Severity Index 100 (PASI 100)‐‐‐‐‐‐Timepoint: Proportion of patients simultaneously achieving ACR50 and PASI 100 ; at Week 24 ; SECONDARY OUTCOME: To assess whether ixekizumab ; is noninferior to adalimumab at Week 24 in the treatment of ; patients with active PsA as ; measured by ACR50‐‐‐‐‐‐Timepoint: Proportion of patients achieving ACR50 in each treatment group at Week 24 To assess whether ixekizumab ; is superior to adalimumab at ; Week 24 in the treatment of ; patients with active PsA as ; measured by PASI 100‐‐‐‐‐‐Timepoint: Proportion of patients achieving PASI 100 in each treatment group at Week 24 INCLUSION CRITERIA: 1] Are male or female patients 18 years or older [1a] Male patients agree to use a reliable method of birth control during the study. [1b] Female patients: Are women of childbearing potential who test negative for pregnancy and agree to use a reliable method of birth control or remain abstinent during the study and for at least 12 weeks after the last dose of investigational product, whichever is longer. Methods of contraception considered acceptable when used properly include oral contraceptives, contraceptive patch, injectable or implantable contraceptives, intrauterine device, vaginal ring, diaphragm with contraceptive gel, or condom with contraceptive foam. OR Are women of non childbearing potential, defined as: Women who have had surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation); OR Women who are â?¥60 years of
The main purpose of this study is to evaluate the effectiveness and safety of ixekizumab versus adalimumab in participants with psoriatic arthritis (PsA) who are biologic disease-modifying anti-rheumatic drugs (DMARD) naive.
Background: There have been few head-to-head clinical trials comparing different biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients (pts) with psoriatic arthritis (PsA). Objectives: To report 24-week (wk) results of a study directly comparing efficacy and safety of ixekizumab (IXE), an IL-17A inhibitor, and adalimumab (ADA), a TNF inhibitor, in bDMARD-naive pts with PsA. Methods: The study (NCT03151551; SPIRIT-H2H) included pts with active PsA (≥3 TJC + ≥3SJC) and plaque psoriasis (BSA≥3%) who were bDMARD naive and inadequate responders to csDMARD therapy. Patients were randomised (1:1) to IXE or ADA for 52 wks (on-label dosing based on presence/absence of moderate to severe psoriasis). The primary objective was superiority of IXE vs ADA measured by the proportion of pts achieving both ACR50 and PASI100 responses at wk24. Key secondary objectives versus ADA at wk 24 were (1) non-inferiority of IXE for ACR50 (noninferiority margin -12%) and (2) superiority of IXE for PASI100. Additional PsA, skin, composite treat-to-target (T2T: MDA, DAPSA 4), PASDAS remission and patient-reported outcomes, and safety were assessed. Nine pts had PASI=0 and BSA≥3% (a medical inconsistency) at baseline; these pts were considered PASI100 responders if PASI=0 and BSA=0 at wk 24. Categorical variables were evaluated using logistic regression analyses with NRI in the ITT population. Continuous variables were analysed using mixed models for repeated measure analysis. Results: 566 pts were randomised (283 to IXE and 283 to ADA). Baseline demographics and disease characteristics were generally well balanced between groups (Table 1). All primary and key secondary efficacy endpoints at wk 24 were met (Figure). The proportion of pts achieving both ACR50 and PASI100 was significantly greater for IXE than ADA (36% vs 28%; p<0.05). IXE was non-inferior to ADA for ACR50 response and superior for PASI100 response (Figure). While improvements from baseline were achieved with both treatments, significantly better results were seen with IXE vs ADA for skin and composite T2T outcomes, enthesitis resolution (Figure 1), and skin-related quality of life (Table 2). No unexpected safety signals were observed. (Table Presented) Conclusion: In bDMARD naive pts with active PsA and skin disease, IXE showed superior efficacy to ADA based on simultaneous achievement of ACR50 and PASI100 responses at wk 24. Greater improvements with IXE vs ADA were also attained in individual PsA domains and composite T2T outcomes.
Background: Multiple biologic DMARDs (bDMARDs) are available for the treatment of psoriatic arthritis (PsA), but there are few direct comparisons of their efficacy and safety. In SPIRIT-H2H study, ixekizumab (IXE), a high-affinity monoclonal antibody selectively targeting IL-17A, was superior to adalimumab (ADA) at Week 24 for simultaneous achievement of ACR50 and 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI 100) in patients (pts) with active PsA. Efficacy on other PsA domains was shown.1 Objectives: To provide individual patient data demonstrating the simultaneous improvement in musculoskeletal and skin symptoms as assessed by American College of Rheumatology (ACR) response criteria and Psoriasis Area and Severity Index (PASI) percent improvement, respectively. Methods: Pts with active PsA fulfilling Classification for Psoriatic Arthritis (CASPAR) criteria, ≥3/66 tender and ≥3/68 swollen joints, ≥3% psoriasis body surface area (BSA) involvement, no prior treatment with bDMARDs, and prior inadequate response to ≥1 conventional synthetic DMARD (csDMARD), were randomized 1:1 to open-label IXE or ADA (label dosing according to presence/absence of moderate-to-severe psoriasis [baseline BSA≥10%, PASI≥12, and static Physician's Global Assessment≥3]) in Study I1F-MC-RHCF (NCT03151551). In this analysis, max ACRx was defined as the maximum ACRx response a patient can achieve where ACRx derivation follows the typical ACR response criteria: ≥x% improvement in both tender joint count (TJC) and swollen joint count (SJC) and ≥x% improvement in ≥3 of the 5 remaining components, Health Assessment Questionnaire-Disability Index total score (HAQ-DI), C-reactive protein (CRP), Patient Global Assessment (PatGA), Physician Global Assessment (PhyGA), and patient assessment of joint pain (patJP). Missing data were imputed using the last observation carried forward (LOCF) method. Results: At baseline, demographic and disease characteristics were similar across treatment groups. Mean baseline values for the ACR core data set were 20.2 (TJC), 10.4 (SJC), 63.8 (PatGA), 10.2 (CRP), 59.2 (PhyGA), 1.2 (HAQ-DI), and 61.0 (patJP). Mean PASI total score was 7.8. Figures 1 and 2 show the maximum ACR response by PASI percent improvement at Weeks 24 and 52, respectively. Independent of joint improvement, more ixekizumab-treated patients compared to adalimumab-treated patients achieved ≥PASI 90 (76.6% vs. 57.5% at week 24 and 83.0% vs. 59.6% at Week 52). Evaluation of patient-level data shows that while very few patients had joint improvement but little skin improvement (max ACRx≥50 and PASI<50; Figures 1 and 2) in both treatment arms (IXE: 1.8%; ADA: 1.4%), fewer patients treated with IXE had no to little improvement in both joint and skin symptoms (PASI<50 and max ACRx<50) than those treated with ADA at Week 24 (IXE: 3.6%; ADA: 13.3%). A similar pattern was observed at Week 52 (Figure 2). Conclusion: Ixekizumab treatment was superior to adalimumab when evaluating the combination of musculoskeletal and skin symptoms of PsA as measured by ACR response and PASI response.
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).1 Objectives: 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 naive 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%; p<0.001), and the time to develop a patient's first SAE was significantly shorter for ADA versus IXE (p<0.001; Figure). Discontinuations due to AEs were numerically more frequent in the ADA group versus the IXE group (7.4% vs 4.2%; p=0.15). IXE-treated patients reported more injection-site reactions (ISR) than ADA-treated patients (11% vs. 3.5%; p=0.002). Study withdrawals due to ISR were comparable, and only one injection-site reaction was severe on ADA (Table). There were two IBD cases reported for IXE; one case was confirmed as IBD. Conclusion: 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.
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 naive 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 ADAtreated 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,2,3 consistent 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.
<b>OBJECTIVES: </b>SPIRIT 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.<b>METHODS: </b>SPIRIT-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.<b>RESULTS: </b>A significantly higher proportion of patients treated with IXE versus ADA simultaneously achieved ACR50 and PASI100 (39% vs 26%, p<0.001), PASI100 (64% vs 41%, p<0.001) at Wk52. Efficacy of IXE and ADA was similar at Wk52 for ACR50 (49.8% vs 49.8%, p=0.924), treat-to-target outcomes, enthesitis and dactylitis resolution. Responses to IXE were consistent irrespective of concomitant csDMARD use. Significantly more patients on IXE monotherapy versus ADA monotherapy had simultaneous ACR50 and PASI100 (38% vs 19%, p=0.007), and PASI100 responses (66% vs 35%, p<0.001) at Wk52. There were no new safety findings for IXE or ADA.<b>CONCLUSIONS: </b>IXE 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.<b>Trial Registration Number: </b>NCT03151551.
Objective: Nail psoriasis is common in patients with psoriatic arthritis (PsA) and plaque psoriasis (PsO), causing pain and impaired hand mobility. This analysis evaluated the efficacy of two biologic disease-modifying antirheumatic drugs (bDMARDs), ixekizumab and adalimumab, for treating nail psoriasis in patients with active PsA and moderate to severe PsO (Psoriasis Area and Severity Index score ≥12, static Physicians Global Assessment score ≥3 and body surface area involvement ≥10%). Methods: SPIRIT-H2H was a randomised, open-label, rater-blinded study evaluating the efficacy and safety of ixekizumab versus adalimumab in adults with active PsA and PsO naïve to bDMARDs. This post hoc subgroup analysis examined the efficacy of both treatments in PsA patients with moderate to severe PsO and nail psoriasis (baseline Nail Psoriasis Severity Index (NAPSI) score ≥1). Differences in NAPSI scores between treatments (mixed models for repeated measurement), and the proportions of complete responders (NAPSI score 0; logistic regression model) were determined to 24 weeks. Results: Baseline NAPSI scores were ≥ 1 in 75.5% of the analysis population receiving ixekizumab (37/49) and 80.4% receiving adalimumab (41/51), ≥16 in 56.8% and 58.5%, and ≥40 in 27.0% and 17.1%, respectively. NAPSI scores improved for both treatments throughout the study, with a numerically greater reduction from baseline (−20.7 vs −16.3, P =.076) and significantly greater proportion of complete responders (80.0% vs 52.5%; P =.009) with ixekizumab than adalimumab at week 24. Conclusions: In this post hoc analysis, ixekizumab showed higher rates of complete resolution of nail involvement than adalimumab at week 24, confirming the established efficacy of ixekizumab in nail 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 (<10%, ≥10%) and CRP (≥ 6 mg/ L,>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 IXEtreated 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 (<10%, p=0.010; ≥10%, p=0.003) was significantly greater in IXE vs ADA (table). Significantly more IXE-treated patients vs ADA achieved MDA with baseline enthesitis (p=0.002), without dactylitis (p=0.015), with fingernail psoriasis (p<0.001), CRP ≥6 mg/L (p=0.046) and BSA ≥10% (p=0.01) (table). A limitation is that this analysis was completed post-hoc, not controlled for multiplicity, and patients were not stratified by baseline disease characteristics. 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.
Ixekizumab (IXE), a selective interleukin 17A antagonist, is approved for the treatment of adults with moderate‐to‐severe psoriasis (PsO), and active psoriatic arthritis (PsA). The efficacy of IXE was compared with adalimumab (ADA) in patients with PsA and concomitant PsO in the SPIRIT‐H2H (NCT03151551) study. SPIRIT‐H2H was a multicentre, randomized, open‐label, rater‐blinded, parallel‐group study. Biological disease‐modifying anti‐rheumatic drug (DMARD)‐naïve patients (n = 566) with PsA and active PsO [≥ 3% body surface area (BSA) involvement] were randomized to IXE or ADA, stratified by concomitant use of conventional synthetic DMARDs and severity of PsO. Patients with moderate‐to‐severe PsO [Psoriasis Area Severity Index (PASI) ≥ 12, static Physician's Global Assessment score ≥ 3 and BSA involvement ≥ 10%] received either IXE [160 mg at week 0, 80 mg every 2 weeks (Q2W) up to week 12 then every 4 weeks] or ADA (80 mg at week 0, 40 mg Q2W starting at week 1). The primary endpoint was the proportion of patients simultaneously achieving ≥ 50% improvement in American College of Rheumatology criteria (ACR50) and 100% improvement from baseline in PASI (PASI100) at week 24. Here we report efficacy outcomes between IXE and ADA, compared using Fisher's exact test, through week 52 in a subgroup of patients with moderate‐to‐severe PsO. Missing data were imputed using nonresponder imputation. At baseline, 49 of 283 IXEand 51 of 283 ADA‐treated patients had concomitant moderate‐to‐severe PsO. Of these, 40.8% of patients treated with IXE and 17.6% treated with ADA achieved the primary endpoint at week 24 (P = 0.015). At week 52, 38.8% of IXE‐ and 17.6% of ADA‐treated patients concomitantly achieved ACR50 and PASI100 (P = 0.026). Regarding efficacy endpoints for PsA, the proportion of patients achieving ACR20/ACR50/ACR70 was 73.5%, 55.1% and 42.9% for IXE vs. 80.4%, 62.7% and 39.2% for ADA, respectively (P = 0.480; P = 0.542; P = 0.839). Complete skin clearance, as measured by PASI100, was reached in 59.2% of IXE‐ and 25.5% of ADA‐treated patients (P = 0.001). PASI90 response rates were significantly higher with IXE compared with ADA (81.6% vs. 60.8%; P = 0.028), while no significant differences were seen in PASI75 response rates (85.7% vs. 80.4%; P = 0.597). Other secondary endpoints, including the proportions of patients achieving a Dermatology Life Quality Index of 0 or 1, and complete clearance of nail psoriasis, were numerically higher in the IXE than ADA group, but were not significantly different. In patients with PsA and moderate‐to‐severe PsO, the significantly greater combined response (ACR50 + PASI100) shown for IXE at week 24 was sustained through week 52 and was consistent with results observed in the overall SPIRIT study population.
<b>OBJECTIVES: </b>To compare efficacy and safety of ixekizumab (IXE) to adalimumab (ADA) in biological disease-modifying antirheumatic drug-naïve patients with both active psoriatic arthritis (PsA) and skin disease and inadequate response to conventional synthetic disease-modifying antirheumatic drug (csDMARDs).<b>METHODS: </b>Patients with active PsA were randomised (1:1) to approved dosing of IXE or ADA in an open-label, head-to-head, blinded assessor clinical trial. The primary objective was to evaluate whether IXE was superior to ADA at week 24 for simultaneous achievement of a ≥50% improvement from baseline in the American College of Rheumatology criteria (ACR50) and a 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI100). Major secondary objectives, also at week 24, were to evaluate whether IXE was: (1) non-inferior to ADA for achievement of ACR50 and (2) superior to ADA for PASI100 response. Additional PsA, skin, treat-to-target and quality-of-life outcome measures were assessed at week 24.<b>RESULTS: </b>The primary efficacy endpoint was met (IXE: 36%, ADA: 28%; p=0.036). IXE was non-inferior for ACR50 response (IXE: 51%, ADA: 47%; treatment difference: 3.9%) and superior for PASI100 response (IXE: 60%, ADA: 47%; p=0.001). IXE had greater response versus ADA in additional PsA, skin, nail, treat-to-target and quality-of-life outcomes. Serious adverse events were reported in 8.5% (ADA) and 3.5% (IXE) of patients.<b>CONCLUSIONS: </b>IXE was superior to ADA in achievement of simultaneous improvement of joint and skin disease (ACR50 and PASI100) in patients with PsA and inadequate response to csDMARDs. Safety and tolerability for both biologicals were aligned with established safety profiles.
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.
Background: Ixekizumab (IXE), a high-affinity monoclonal antibody targeting IL-17A, has demonstrated superiority in achieving the combined endpoint of ACR50 and PASI100 at week (Wk) 24 compared to adalimumab (ADA) in the SPIRIT-H2H trial [1]. In this analysis, we looked at the efficacy responses at the individual patient (pt) level to assess consistency over time and at each visit. Objectives: To determine the American College of Rheumatology 50% (ACR50) response and Disease Activity in psoriatic arthritis (PsA) (DAPSA) response in pts treated with IXE and describe response consistency over time and at each visit from Wk 24 through Wk 52. Methods: This post-hoc analysis used data from SPIRIT-H2H (NCT03151551), a phase3b/4 randomised, open-label parallel-group study between IXE and ADA. Pts were randomised to receive either IXE 80 mg, every 4 Wks (IXE Q4W)) or ADA 40 mg, every 2 Wks (ADA Q2W)). The proportion (%) of pts in the intent-to-treat population who achieved each endpoint, either ACR50 or DAPSA≤14, at Wk 24 and at each post-baseline visit out to Wk 52 was assessed. Nine pts with active psoriasis and body surface area (BSA) ≥3% were assessed as PASI=0 at baseline, a medical inconsistency that was resolved using medical judgement. These pts were considered PASI100 responders if PASI=0 and BSA=0 at post baseline visits. Results: A total of 566 patients enrolled in the trial received either IXE (N=283) or ADA (N=283). Of the 143 pts treated with IXE who achieved ACR50 at Wk 24, 65% (N=93) maintained ACR50 at every visit. In total, 83% (N=118) of the ACR50 achievers at Wk 24 maintained ACR50 with some (18% (N=25)) fluctuations, between ACR50 and ACR20 (Figure 1). Of the 132 pts treated with ADA who achieved ACR50 at Wk 24, 55% (N=72) maintained ACR50 at every visit. In total, 80% (N=105) of ACR50 achievers maintained ACR50 with some (25% (N=33)) fluctuations between ACR50 and ACR20 (Table 1). Furthermore, of the174 pts treated with IXE who achieved low DA (DAPSA≤14) at Wk 24, 68% (N=119) maintained low DA at every visit. Of the low DA achievers at Wk 24, 82% (N=142) of pts maintained low DA with some (13% (N=23)) fluctuations between moderate and low DA (Figure 1B). Of the 171 pts treated with ADA who achieved low DA at Wk 24; 57% (N=97) maintained low DA at every visit. In total, 77% (N=131) of low DA achievers at Wk 24 maintained low DA with some (20% (N=34)) fluctuations between moderate and low DA (Table 1). Conclusion: This analysis demonstrates that a numerically higher proportion of pts treated with IXE versus ADA show consistency of response, as measured by ACR50 and DAPSA responses, over time and for each visit at the pt level.
Background/AimsIxekizumab (IXE), is approved for of active PsA, moderate-to-severepsoriasis (PsO), and radiographic/non-radiographic axial SpA treatment in adults. Efficacy of IXE was compared to adalimumab (ADA) inpatients (pts) with PsA and concomitant PsO in SPIRIT-H2H(NCT03151551). We report results at week (wk) 24 and 52 fromsubgroup analysis based on baseline PsO severity.MethodsSPIRIT-H2H was a 52-wk, multicenter, randomized, open-label, raterblinded, parallel-group study of biologic DMARD-naïve pts (N = 566)with PsA and active PsO (3% body surface area). Pts wererandomized (stratified by concomitant use of conventional syntheticDMARDs and PsO severity) to IXE or ADA. Pts received on labeldosing according to PsO severity. We report efficacy outcomes at wk24 and 52 for subgroup analysis of patients with/without moderate-tosevere PsO at baseline. The primary endpoint was the proportion ofpts simultaneously achieving ACR50 and PASI PASI100 at wk 24.Additional post-hoc analysis was performed for other endpoints.Logistic regression models were performed with treatment, baselinePsO severity and treatment-by-baseline PsO severity interaction asindependent variables. Differences in the proportion of responderswere assessed using Fisher's exact test.ResultsAt baseline, 49/283 IXE-treated pts and 51/282 ADA-treated pts hadmoderate-to-severe PsO. A greater proportion of IXE-treated ptsachieved the combined endpoint of ACR50+PASI100, and PASI100compared to ADA at wk 24 and 52, regardless of baseline PsO severity(Table). Similar efficacy was observed on joints for IXE and ADA acrosssubgroups. Faster improvement was observed for IXE vs. ADA inminimal disease activity (MDA) and Disease Activity in PsoriaticArthritis (DAPSA) remission regardless of PsO severity, and very lowdisease activity (VLDA) in pts with moderate-to-severe PsO. Other efficacy outcomes by subgroup based on PsO severity atbaselineConclusionIn pts with active PsA, a significantly higher proportion of IXE-treatedpts achieved the combined ACR50+PASI100 endpoint, and PASI100at wk 52 vs. ADA, regardless of baseline PsO severity. ACR50response at wk 24 and 52 was not influenced by IXE dosing. Fasterimprovements in MDA and DAPSA remission were observed with IXEthan with ADA. These results were consistent with the overall SPIRITH2H population.
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.
Main Objective: To assess whether ixekizumab; is superior to adalimumab at; Week 24 in the treatment of; patients with active PsA as; measured by American College of Rheumatology 50 (ACR50); and Psoriasis Area and Severity; Index 100 (PASI 100) Primary end point(s): Proportion of Participants Simultaneously Achieving American College of Rheumatology (ACR)50 and Psoriasis Area and Severity Index (PASI)100 ; Secondary Objective: To assess whether ixekizumab is noninferior to adalimumab at; Week 24 in the treatment of patients with active PsA as; measured by ACR50; ; To assess whether ixekizumab; is superior to adalimumab at; Week 24 in the treatment of; patients with active PsA as; measured by PASI 100; ; To assess the effect of treatment with ixekizumab compared with adalimumab over 52 weeks as measured by various efficacy and quality of life outcomes Timepoint(s) of evaluation of this end point: Week 24
INCLUSION CRITERIA:
Presents with established diagnosis of active psoriatic arthritis for at least 6 months, and currently meets Classification for Psoriatic Arthritis (CASPAR) criteria Active psoriatic arthritis (PsA) defined as the presence of at least 3 tender and at least 3 swollen joints Presence of active plaque psoriasis Men must agree to use a reliable method of birth control or remain abstinent during the study Women must agree to use reliable birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 495 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55
SECONDARY OUTCOME:
Secondary end point(s): Proportion of Participants Achieving ACR50 ; ; Proportion of Participants Achieving PASI100 ; ; Change from Baseline in Tender Joint Count (TJC) ; ; Change from Baseline in Swollen Joint Count (SJC) ; ; Change from Baseline in Participant's Assessment of Pain VAS ; ; Change from Baseline in Participant's Global Assessment of Disease Activity ; ; Change from Baseline in Physician's Global Assessment of Disease Activity ; ; Change from Baseline in C‐Reactive Protein (CRP) ; ; Change from Baseline in Health Assessment Questionnaire‐Disability Index (HAQ‐DI) ; ; Proportion of Participants Simultaneously Achieving ACR50 and PASI100 ; ; Change from Baseline in Disease Activity Score‐CRP (DAS28‐CRP) ; ; Proportion of Participants Achieving Minimal Disease Activity (MDA) ; ; Proportion of Participants Achieving Psoriatic Arthritis Response Criteria (PsARC) ; ; Change from Baseline in Modified Composite Psoriatic Disease Activity Index (CPDAI) Score (Modified) ; ; Change from Baseline in the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index in Participants with Enthesitis at Baseline ; ; Change from Baseline in the Leeds Enthesitis Index (LEI) in Participants with Enthesitis at Baseline ; ; Change from Baseline in the Leeds Dactylitis Index‐Basic (LDI‐B) in Participants with Dactylitis at Baseline ; ; Change from Baseline in Psoriasis Body Surface Area (BSA) ; ; Change from Baseline in the Nail Psoriasis Severity Index (NAPSI) Fingernails Score in the Subgroup of Participants with Fingernail Involvement at Baseline ; ; Change from Baseline in the Itch NRS; ; Change from Baseline in Fatigue Severity NRS (Fatigue NRS) Score ; ; Change From Baseline in Medical Outcomes Study 36‐item Short Form Health Survey (SF‐36): Physical Component Summary (PCS) and Mental Component Summary (MCS) ; ; Change from Baseline in Measures of Health Utility (EuroQol‐5 Dimensions 5 Level [EQ‐5D 5L]) ; ; Change from Baseline in Dermatology Life Quality Index (DLQI) Total Score; ; Change from Baseline on the Treatment Satisfaction Questionnaire ; ; Change from Baseline in Columbia Suicide Severity Rating Scale (C‐SSRS) Timepoint(s) of evaluation of this end point: Week 24 and 52
