Six-Month Real-World Study to Assess the Effectiveness of Ixekizumab After Switching from IL-23 Inhibitors and Other Biologic Therapies: The CorEvitas Psoriasis Registry.

BACKGROUND: Prior work showed that patients from the CorEvitas Psoriasis Registry who had previously failed a prior biologic and then initiated ixekizumab demonstrated improvements in disease severity and patient-reported outcomes after 6 months. However, newer therapies such as interleukin-23 inhibitors (IL-23i) were not considered. Here, with more recent data including IL-23i, 6-month effectiveness of ixekizumab following a switch from any biologic was assessed as well as whether 6-month effectiveness of ixekizumab was impacted by prior biologic class. METHODS: We included CorEvitas Psoriasis Registry patients who initiated ixekizumab after discontinuing another biologic therapy and had a corresponding 6-month follow-up visit following ixekizumab initiation (N = 743, 2016-2023). Immediate prior biologic class was categorized as tumor necrosis factor inhibitor (TNFi) or interleukin-12/23 inhibitors (IL-12/23i, n = 405), non-ixekizumab interleukin-17i (IL-17i, n = 237), or IL-23i (n = 101). Adjusted mean changes in body surface area (BSA), Dermatology Life Quality Index (DLQI), itch, and skin pain were calculated for prior biologic class groups using analysis of covariance (ANCOVA). Proportions achieving ≥ 75%, ≥ 90%, and ≥ 100% improvement in Psoriasis Area and Severity Index (PASI75, PASI90, and PASI100, respectively), Investigator's Global Assessment (IGA) 0/1, and DLQI 0/1 were calculated for all patients and compared among prior biologic classes via relative risks (RRs) and 95% confidence intervals (CIs) using multivariable modified Poisson regression. RESULTS: Mean improvements in BSA, DLQI, itch, and skin pain, were 7.6, 3.6, 23.3, and 16.7, respectively, for ixekizumab patients who switched from TNFi or IL-12/23i (all p < 0.05); 6.8, 3.3, 19.6, and 14.1, respectively, for those who switched from non-ixekizumab IL-17i (all p < 0.05); and 7.8, 3.4, 22.2, and 12.8, respectively, for those who switched from IL-23i (all p < 0.05). Overall, 54%, 41%, and 31% of ixekizumab initiators achieved PASI75, PASI90, and PASI100, respectively, 50% maintained or achieved IGA 0/1, and 48% maintained or achieved DLQI 0/1. The prior TNFi or IL-12/23i group was 31% more likely to achieve PASI100 (RR = 1.31, 95% CI 1.01, 1.69) and 32% more likely to maintain or achieve IGA 0/1 (RR = 1.32, 95% CI 1.11, 1.57), but not significantly more likely to achieve PASI90. The prior IL-23i group was 45% more likely to achieve PASI90 (RR = 1.45, 95% CI 1.10, 1.91), 55% more likely to achieve PASI100 (RR = 1.55, 95% CI 1.12, 2.13), and 39% more likely to maintain or achieve IGA 0/1 (RR = 1.39, 95% CI 1.12, 1.73) compared to the prior non-ixekizumab IL-17i group. Achievement of PASI75 and DLQI 0/1 was consistent across the prior TNFi or IL-12/23i, IL-23i, and non-ixekizumab IL-17i groups. CONCLUSIONS: These updated findings with IL-23i data reaffirm that patients with psoriasis who switch to ixekizumab after discontinuing another biologic demonstrate improvement in disease severity and patient-reported outcomes at 6 months in real-world settings. Compared to patients who switched from another IL-17i, patients who switched class from a TNFi or IL-12/23i were more likely to achieve PASI100 and IGA 0/1, and patients who switched class from an IL-23i were more likely to achieve PASI90 in addition to PASI100 and IGA 0/1.

Ixekizumab Demonstrates Rapid and Consistent Efficacy for Patients with Psoriatic Arthritis, Regardless of Psoriasis Severity.

INTRODUCTION: Skin involvement in patients with psoriatic arthritis (PsA) worsens the severity and burden of disease. Ixekizumab (IXE), a selective interleukin (IL)-17A antagonist, was compared to placebo (PBO) in the SPIRIT-P1 (NCT01695239) and SPIRIT-P2 (NCT02349295) studies in patients with PsA and evidence of plaque psoriasis. This post hoc analysis reports musculoskeletal, skin, and nail outcomes through week 24 in patients from SPIRIT-P1 and SPIRIT-P2, stratified by mild, moderate, or psoriasis at baseline. METHODS: This post hoc analysis pooled patients from SPIRIT-P1 and SPIRIT-P2 who were randomly assigned to PBO or IXE 80 mg every 4 weeks (Q4W) or every 2 weeks (Q2W). Efficacy outcomes were analyzed through week 24 by baseline psoriasis severity, defined by percent body surface area (BSA) affected; mild = BSA < 3%, moderate = 3% ≤ BSA ≤ 10%, severe = BSA > 10%. The primary outcomes assessed were the proportion of patients achieving American College of Rheumatology (ACR)20, ACR50, and ACR70 responses. Secondary outcomes included musculoskeletal, disease activity, skin and nail, and health-related quality-of-life measures. RESULTS: Similar proportions of patients achieved ACR20/ACR50/ACR70 over time across all severity subgroups and treatment arms. More than one-third of IXE-treated patients achieved ACR20 at week 4, or ACR50 at week 24, with no significant differences according to psoriasis severity at baseline. Disease activity outcomes were similar through week 24 with both IXEQ4W and IXEQ2W, regardless of psoriasis severity at baseline. There were no significant differences over 24 weeks in the proportions of IXE-treated patients with mild, moderate, or severe baseline psoriasis who achieved Minimal Disease Activity (MDA). Across all severity subgroups, IXE demonstrated Psoriasis Area Severity Index 100 response as early as week 4, and approximately one-third of IXE-treated patients achieved total skin clearance at week 24. CONCLUSION: IXE demonstrated rapid and consistent efficacy in joint, skin, and nail for patients with PsA, regardless of baseline psoriasis severity. TRIAL REGISTRATION: SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295).

Effectiveness of bDMARDs in ankylosing spondylitis patients by biologic use: experience from the CorEvitas PsA/SpA Registry.

OBJECTIVE: To describe bDMARD initiators by biologic experience among ankylosing spondylitis (AS) patients and change in disease activity and patient-reported outcomes (PROs) in real-world US patients. METHODS: We included patients ≥18 years with AS based on physician diagnosis enrolled between 3/2013 and 11/2019 in the CorEvitas Psoriatic Arthritis (PSA)/Spondyloarthritis Registry (NCT02530268). Patients concurrently diagnosed with PSA were excluded. Baseline (bDMARD initiation) demographics, comorbidities, disease characteristics, treatment, and PROs were collected. Response rates and changes in disease activity and PROs between baseline and 6- and 12- month follow-up visits were calculated. RESULTS: Of the 489 AS patients in the PsA/SpA Registry, 254 AS (52.0%) patients initiated a bDMARD at enrollment or during follow-up (total initiations: AS = 313). Of the 313 AS initiations, 179 (57.2%) had a 6-month follow-up, 122 (39.0%) had a 12-month follow-up, and 94 (30.0%) had a 6- and 12-month follow-up visit. For those AS initiators with a 6-month follow-up, the mean age was 49.1 years, 44.4% were female, and 70.4%, 47.5%, 96.1%, and 46.9% had never used cDMARDs, TNFis, non-TNFis, and bDMARDs, respectively. Of these 179 AS initiators, 20.1% and 14.0% achieved ASAS20/40, respectively. Further, only 34% achieved low disease activity (ASDAS <2.1). When stratified by biologic-naivete and biologic-experience, the ASAS 20/40 achievement rates were 26.2% and 14.7%, and 21.4% and 7.4%, respectively, for this cohort. CONCLUSION: Although AS patients initiate bDMARDs, many do not achieve optimal treatment responses. Future research is needed to investigate the aspects associated with inadequate improvement and treatment response to bDMARDs.

Treatment patterns and health care costs among patients with psoriatic arthritis treated with biologic or targeted synthetic disease-modifying antirheumatic drugs.

BACKGROUND: Biologic and targeted synthetic disease-modifying antirheumatic drug (tsDMARD) therapies are used in management of psoriatic arthritis (PsA). Although previous studies have demonstrated that rates of adherence, persistence, discontinuation, and switching, as well as health care costs, are variable among treatments, limited published data exist on more recently approved therapies. OBJECTIVE: To describe adherence, persistence, discontinuation, reinitiation, switching, dosing patterns, and health care costs among PsA patients treated with biologics and tsDMARDs. METHODS: This was a real-world, retrospective administrative claims study. Adult PsA patients with at least 1 claim for an approved PsA biologic (adalimumab, certolizumab, etanercept, golimumab, infliximab, secukinumab, or ustekinumab) or tsDMARD (apremilast or tofacitinib) between January 1, 2015, and June 30, 2019, were selected from the IBM MarketScan administrative claims databases. The first claim for one of the study treatments determined the index date and drug cohort. Patients were required to be continuously enrolled in their health plans for 12 months before and after the index date and to have at least 1 claim with a diagnosis of PsA in the 12 months before or on the index date. Adherence (measured by proportion of days covered [PDC] and medication possession ratio [MPR]), persistence (< 60-day gap in treatment), discontinuation (> 90-day gap), reinitiation of index drug, switching, and dosing patterns for each index drug were assessed during the 12-month follow-up period. Health care costs were reported per patient per month (PPPM) during the 12-month follow-up and assessed after adjusting PsA treatment costs by the Institute for Clinical and Economic Review discount factors to account for discounts and rebates not usually reflected in claims data and by adherence. RESULTS: Overall, 6,674 patients met the selection criteria. The top 3 index drugs were adalimumab (37%), apremilast (26%), and etanercept (18%). Over 12 months of follow-up, 31%-59% of patients remained persistent on the index drug, whereas 35%-56% discontinued, 13%-29% switched to a different biologic or tsDMARD, and 3%-15% reinitiated the index therapy, depending on the index drug. The mean PDC ranged from 0.51 to 0.69 during the 12-month follow-up and 0.80 to 0.93 during the follow-up period before discontinuation. Dose values were largely consistent with prescribing information, with the exception of secukinumab. Index drug costs PPPM ranged from $2,361 (apremilast) to $6,528 for ustekinumab after adjustment for discounts and adherence. CONCLUSIONS: Results from this real-world analysis suggest that there is substantial variability in persistence, discontinuation, adherence, reinitiating, and switching patterns among the different biologic and tsDMARD treatment options for PsA patients. In addition, this study provides real-world cost data for biologics and tsDMARDs among patients with PsA. DISCLOSURES: This study was funded by Eli Lilly Inc., which participated in analysis and interpretation of data, drafting, reviewing, and approving the publication. All authors contributed to the development of the publication and maintained control over the final content. Murage, Malatestinic, Zhu, Atiya, Kern, Stenger, and Sprabery are employees and stockholders of Eli Lilly Inc. Princic and Park are employed by IBM Watson Health, which received funding from Eli Lilly Inc. to conduct this study. Ogdie has received consulting fees from Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Corrona, Janssen, Lilly, Novartis, and Pfizer and has also received grant support from Pfizer, Novartis, and Amgen. Portions of these data have been presented in poster form at the virtual International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2020 and Congress of Clinical Rheumatology (CCR) West 2020 conferences.

Disease response and patient-reported outcomes among initiators of ixekizumab.

OBJECTIVES: There is limited real-world evidence on using ixekizumab in psoriasis patients. Therefore, we characterized patients with psoriasis initiating ixekizumab and report 6-month changes in disease and patient-reported outcomes. METHODS: Adult patients with psoriasis who initiated ixekizumab and completed a 6-month follow-up visit were enrolled from the Corrona Psoriasis Registry. Disease characteristics and outcomes were assessed at ixekizumab initiation. Outcomes included the mean 6-month change in Psoriasis Area and Severity Index (PASI), body surface area (BSA), Investigator Global Assessment (IGA), and IGA*BSA. RESULTS: From baseline to follow-up in all patients (n = 136), means decreased for IGA*BSA (-45.5) and BSA (-12.4), and a higher % achieved an absolute PASI ≤ 5 (84.6%), BSA 0-3 (72.1%), and IGA 0/1 (50.7%). Within stratified groups, means decreased for PASI <12 for IGA*BSA (-21.1) and BSA (-6.3); PASI≥12 for IGA*BSA (-94.8) and BSA (-24.6); weight <100 kg for IGA*BSA (-45.1) and BSA (-12.4); weight ≥100 kg for IGA*BSA (-46.2) and BSA (-12.3); concomitant PsA for IGA*BSA (-56.0) and BSA (-15.3); and in no concomitant PsA for IGA*BSA (-36.9) and BSA (-10.0). CONCLUSIONS: We provide real-world evidence on the benefits of ixekizumab for treating psoriasis, regardless of baseline disease severity, weight, or concomitant PsA.

Drug survival of ixekizumab, TNF inhibitors, and other IL-17 inhibitors in real-world patients with psoriasis: The Corrona Psoriasis Registry.

To compare drug survival of ixekizumab to other IL-17 inhibitors (IL-17i) and TNF inhibitors (TNFi) among patients with psoriasis (PsO) in a real-world setting. Participants included adult PsO patients enrolled in the Corrona Psoriasis Registry who initiated ixekizumab, TNFi, or other IL-17i between 16 March 2016 to 10 August 2019 and completed ≥1 follow-up visit. Multivariable adjusted hazard ratios (HR) were calculated to estimate the risk for drug discontinuation in the ixekizumab group relative to the other drugs. Among the 1604 drug initiations, 552 initiated ixekizumab, 450 initiated TNFi, and 602 initiated other IL-17i. Mean age was 51 years, 49% were women, and 52% were obese (BMI > 30). Ixekizumab patients had a higher proportion of patients with PASI >12 at drug initiation (24%) than TNFi (15%) and other IL-17i (19%). Over a median of 11 months of follow-up, 723/1604 (45%) drug discontinuations occurred. Persistence of ixekizumab, TNFi, and other IL-17i at 24-months were 68%, 33%, and 46%, among biologic-naïve patients (n = 543), and 46%, 23%, and 36%, for biologic-experienced patients (n = 1061), respectively. Ixekizumab patients had a 64% lower risk of discontinuation vs TNFi (HR = 0.36; 95% CI 0.27-0.47) and a 31% lower risk vs other IL-17i (HR = 0.69, 95% CI 0.55-0.87) after adjustment for biologic experience and other covariates. HRs were similar when limited to patients with moderate-to-severe PsO (BSA > 3, PASI > 3, and IGA > 1, n = 1076) at initiation. In our study of real-world patients with PsO, initiators of ixekizumab had more prolonged drug survival than both initiators of TNFi and other IL-17i up to 2 years of follow-up.

Evaluation of Changes in Skin and Joint Outcomes and Associated Treatment Changes in Psoriatic Arthritis (PsA): Experience From the Corrona PsA/SpA Registry.

OBJECTIVE: To characterize skin severity and joint activity outcomes and associated treatment changes in patients with psoriatic arthritis (PsA) through 12 months of follow-up after enrollment in the Corrona Psoriatic Arthritis/Spondyloarthritis (PsA/SpA) Registry. METHODS: Patients ≥ 18 years of age with a diagnosis of PsA and a history of psoriasis between March 21, 2013, and September 30, 2016, were enrolled (n = 647). Demographics, clinical features, and treatment characteristics were collected and stratified by skin severity and joint activity. Change in joint and skin from enrollment to the 12-month visit was classified by change in category of Clinical Disease Activity Index (CDAI) or body surface area (BSA). Tests of association evaluated the relationship between changes in therapy and changes in skin severity and joint activity. RESULTS: Patients with improvement in both joint activity and skin severity saw the largest median reduction in both CDAI and BSA, while those who worsened in both had the greatest median increase in both CDAI and BSA. The majority of PsA patients (> 50%) had no change in skin severity regardless if they had reduced therapy (50%), no therapy changes (54%), or increased therapy (56%; P = 0.5875). However, there was a significant association between changes in therapy and changes in joint activity (P < 0.001). Patients who increased therapy were more likely to have improvement in joint activity (32%) compared to patients who reduced therapy (22%) or had no therapy changes (11%). CONCLUSION: The clinical implication for our findings suggests the assessment and incorporation of both skin and joint components may be advisable.

Impact of Enthesitis on Psoriatic Arthritis Patient-Reported Outcomes and Physician Satisfaction with Treatment: Data from a Multinational Patient and Physician Survey.

INTRODUCTION: Enthesitis is a core outcome domain assessed in psoriatic arthritis (PsA) clinical trials. Limited evidence describes the impact of enthesitis on patient-reported outcomes (PROs) and physician satisfaction with current treatment options. The objective of this analysis is to characterize the impact of enthesitis on PROs and physician satisfaction with currently available treatment in clinical practice settings. METHODS: Cross-sectional survey of rheumatologists, dermatologists, and their consulting patients with PsA in Australia, Canada, European Union (EU5), and the USA conducted in 2018. Physicians assessed current presence and severity of enthesitis, overall disease severity, other symptoms experienced, and their satisfaction with the current treatment. PsA participant self-reported data included current pain level, EQ5D, Psoriatic Arthritis Impact of Disease (PsAID12), Health Assessment Questionnaire Disability Index (HAQ-DI), and Work Productivity and Activity Impairment Index (WPAI-SHP). Bivariate descriptive analyses were conducted to describe features and outcomes in participants with and without enthesitis. RESULTS: Rheumatologists (454) and dermatologists (238) provided information for 3157 participants with PsA. Mean participant age was 49.2 years, and 45.9% were female. Enthesitis was present currently in 6.5% (205) of participants with PsA. Those with enthesitis had worse overall disease severity compared to those without enthesitis (12.2% vs 2.2% severe) and had more extraarticular manifestations, including nail psoriasis, dactylitis, and sacroiliitis. Enthesitis was associated with more pain, worse quality of life (QoL), increased disability, and a negative impact on work. Participants with enthesitis had higher NSAIDs and opioid pain medication use but similar biologic use. Physicians were significantly less satisfied with current PsA treatment in participants with enthesitis versus without enthesitis. CONCLUSIONS: Participants with psoriatic arthritis with enthesitis experienced significantly higher disease burden than those without enthesitis but were not more likely to receive advanced therapies. Physicians were significantly more dissatisfied with treatment in patients with enthesitis than in those without it.

Medication adherence and persistence in patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis: a systematic literature review.

PURPOSE: Proper adherence and persistence to medications are crucial for better quality of life and improved outcomes in rheumatoid arthritis (RA), psoriasis (PsO), and psoriatic arthritis (PsA). We systematically describe current adherence and persistence patterns for RA, PsO, and PsA, with a focus on biologics and identifying factors associated with adherence and persistence. PATIENTS AND METHODS: Using various databases, a systematic literature review of US-based studies published from 2000 to 2015 on medication adherence and persistence to biologics and associated factors was conducted among patients with RA, PsO, and PsA. RESULTS: Using the medication possession ratio or the percentage of days covered >80%, RA and PsO adherence rates for etanercept, adalimumab, and infliximab ranged from 16% to 73%, 21% to 70%, and 38% to 81%, respectively. Using the criteria of a ≥45-day gap, RA persistence rates for etanercept, adalimumab, and infliximab ranged from 46% to 89%, 42% to 94%, and 41% to 76%, respectively. In PsO, persistence rates for etanercept and adalimumab ranged from 34% to 50% and 50% to 62%, respectively. Similar persistence rates were observed in PsA. Experienced biologics users showed better adherence and persistence. Younger age, female gender, higher out-of-pocket costs, greater disease severity, and more comorbidities were associated with lower adherence and persistence rates. Qualitative surveys revealed that nonpersistence was partly due to perceived ineffectiveness and safety/tolerability concerns. CONCLUSION: Biologic adherence and persistence rates in RA, PsO, and PsA in the United States were low, with significant opportunity for improvement. Various factors - including decrease in disease severity; reduction of comorbidities; lower out-of-pocket costs; refilling at specialty pharmacies; and awareness of drug effectiveness, safety, and tolerability - can inform targeted approaches to improve these rates.