Real-world treatment patterns of immunosuppressants in Adults with systemic lupus erythematosus: A claims database analysis in the United States.

OBJECTIVE: To explore initiation, persistence, and adherence to second-line prescribed treatments for SLE, specifically regarding the immunosuppressants azathioprine, methotrexate, and mycophenolate (conventional DMARDs), and belimumab (a biologic). METHODS: Clinical and insurance records were obtained for 801 patients with SLE who initiated treatment with azathioprine, belimumab, methotrexate, or mycophenolate between July 2015 and June 2019. The date of initiation defined the index date, with a 6-month pre-index and 12-month post-index period. Patient characteristics (age, gender, race, sex, ethnicity, geographic region of the US, diagnosing specialty, and type of insurance) and treatment patterns were tabulated overall and by each index medication. Logistic regression was used to model predictors of persistence for the entire sample and for each treatment cohort. FINDINGS: Approximately one-third of patients initiated methotrexate (n = 282, 35.2%) or mycophenolate (n = 258, 32.2%), with the remaining receiving azathioprine (n = 173, 21.6%) or belimumab (n = 88, 11.0%). 30% of patients were persistent with their index immunosuppressant therapy over the 12-month follow-up. The most common non-persistent treatment pattern was discontinuation which occurred in 55% of patients and was highest in the mycophenolate (58%) and lowest in the azathioprine (47%) groups. In total, 17% of patients switched to a different immunosuppressant, which was highest for the belimumab (25%) group. The average time to discontinuation was over 3 months and average time to switch was about 5 months, with patients receiving azathioprine tending to have shorter and belimumab having longer times to discontinuation or switch.Predictors of persistence were limited. Patients under the care of rheumatologists versus primary care and having higher co-morbidity assessed by CCI were associated with non-persistence for the overall sample. Race, number of SLE-related medications, census region, sex, and age were not found to be significantly related to non-persistence of immunosuppressants in this study.

Patient-reported disease impact of systemic lupus erythematosus with active joint symptoms: Results from the systemic lupus erythematosus-update survey.

BACKGROUND: Many people with systemic lupus erythematosus (SLE) experience joint pain, swelling, and stiffness. These joint symptoms are associated with problems in physical functioning and work disability. We used survey data from adults with SLE to explore the burden and impact of joint symptoms. METHODS: SLE-UPDATE was a 2019 cross-sectional US survey of adults with SLE. We compared respondents with "currently active" joint symptoms' and those "without currently active" joint symptoms. The active joint cohort comprised survey respondents who self-reported current "stiffness in joints" or "pain/swelling in joints" and who had moderate to severe joint pain (Worst Joint Pain Numeric Rating Scale [NRS] score ≥ 4). Respondents not fulfilling these criteria were included in the non-active joint cohort. Outcomes included frequency and severity of pain, patient-reported outcomes (LupusPRO™ and Work Productivity and Activity Impairment: Lupus [WPAI-Lupus]), satisfaction with current treatments, and importance of different treatment goals. RESULTS: More respondents in the active joint cohort (N = 285) than in the non-active joint cohort (N = 215) reported pain most or all the time over the preceding 7 days (77.5% vs. 32.1%, p < .0001), fibromyalgia (45% vs. 12%, p < .0001), and higher (worse) mean scores on the Worst Pain NRS (6.5 vs. 4.8, p < .0001) and Worst Joint Pain NRS (6.7 vs. 4.5, p < .0001). Mean Lupus PRO health-related quality of life (HRQoL) total score was lower (worse) in the active joint cohort (48.9 vs. 64.1, p < .0001). WPAI-Lupus scores indicated greater work productivity losses and activity impairment in the active joint cohort. More respondents in the active joint cohort than in the non-active joint cohort were neutral or not satisfied with current treatments and rated reducing pain as a "very important" treatment goal (26.7% vs. 18.1%). CONCLUSIONS: Respondents with SLE and active joint manifestations in addition to having more pain report lower HRQoL and were less satisfied with their current treatments. Comorbid fibromyalgia may play a role in joint symptoms in patient with SLE joint manifestations. There is an unmet need for new therapeutic options to reduce joint symptom burden among patients with SLE.

Rapid and sustained improvements in patient-reported signs and symptoms with ixekizumab in biologic-naive and TNF-inadequate responder patients with psoriatic arthritis.

OBJECTIVES: To analyse the onset and sustainability of patient-reported improvements in symptoms of psoriatic arthritis (PsA) following treatment with ixekizumab (IXE) up to Week 108. METHODS: In patients with active PsA, either naive to biological DMARDs (SPIRIT-P1) or having inadequate response or intolerance to 1 or 2 prior TNF-inhibitors (TNFi­experienced; SPIRIT-P2), we analysed the change from baseline in joint pain visual analogue scale (VAS; 0-100 scale), patient global assessment (PatGA VAS; 0-100 scale), fatigue numerical rating scale (NRS; 0 [no fatigue] to 10 [worst imaginable]), and Health Assessment Questionnaire-Disability Index (HAQ-DI; 0-3), up to Week 108. RESULTS: IXE-treated patients compared to placebo reported rapid and statistically significant improvement in pain VAS, PatGA, and HAQ-DI as early as Week 1 and this benefit was sustained or increased through Week 108. Fatigue scores improved in IXE-treated patients compared to placebo in both studies; results were statistically significant at Week 24 only in SPIRIT-P2. Improvements in fatigue with IXE were sustained over 2 years. The improvements observed in these patient-reported outcomes (PROs) were consistent in biologic-naive or TNFi-experienced patients. CONCLUSIONS: Patients treated with IXE versus PBO achieved significantly greater improvements and showed faster onset of improvements in patient-reported outcomes measuring symptoms and impact of PsA. Responses were sustained over 2 years and were generally consistent regardless of prior TNFi experience.

Ixekizumab treatment of biologic-naïve patients with active psoriatic arthritis: 3-year results from a phase III clinical trial (SPIRIT-P1).

OBJECTIVE: The aim was to assess the safety and efficacy of up to 156 weeks of ixekizumab (an IL-17A antagonist) treatment in PsA patients. METHODS: In a phase III study, patients naïve to biologic treatment were randomized to placebo, adalimumab 40 mg every 2 weeks (ADA; active reference) or ixekizumab 80 mg every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) after an initial dose of 160 mg. At week 24 (week 16 for inadequate responders), ADA (after 8-week washout) and placebo patients were re-randomized to IXEQ2W or IXEQ4W. Outcomes were evaluated using a modified non-responder imputation [linear extrapolation for radiographic progression (modified total Sharp score = 0)] during extended treatment until week 156. RESULTS: Of 417 patients, 381 entered the extension, and 243 of 381 (63.8%) completed the 156-week study. Incidence rates of treatment-emergent and serious adverse events, respectively, were 38.0 and 5.2 with IXEQ2W (n = 189) and 38.1 and 8.0 with IXEQ4W (n = 197). One death occurred (IXEQ4W). With IXEQ2W and IXEQ4W, respectively, the response rates persisted to week 156 as measured by the ACR response ≥20% (62.5 and 69.8%), ≥50% (56.1 and 51.8%) and ≥70% (43.8 and 33.4%), psoriasis area and severity index (PASI) 75 (69.1 and 63.5%), PASI 90 (64.5 and 51.2%) and PASI 100 (60.5 and 43.6%). Inhibition of radiographic progression also persisted to week 156 in 61% of IXEQ2W and 71% of IXEQ4W patients. CONCLUSION: In this 156-week study of ixekizumab, the safety profile remained consistent with previous reports, and improvements in signs and symptoms of PsA were observed, including persistent low rates of radiographic progression. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01695239, EudraCT 2011-002326-49.

Clinically meaningful improvement in work productivity loss in active psoriatic arthritis: post-hoc analysis of SPIRIT-P1 and SPIRIT-P2 trials.

OBJECTIVES: To determine the proportion of patients in Phase 3 studies (SPIRIT-P1 and SPIRIT-P2) who achieved minimal clinically important difference (MCID) for work productivity loss and activity impairment domains of Work Productivity and Activity Impairment Specific Health Problem (WPAI-SHP) questionnaire. METHODS: In the SPIRIT-P1 study, comprising a 24-week double-blind treatment period, biologic-naive patients with active psoriatic arthritis (PsA) were randomised to ixekizumab 80 mg every 4 weeks (IXEQ4W) or every 2 weeks (IXEQ2W) (starting dose of 160 mg), adalimumab 40 mg every 2 weeks (ADAQ2W), or placebo. SPIRIT-P2 enrolled tumour necrosis factor inhibitor (TNFi)-experienced patients who were randomised to receive IXEQ4W, IXEQ2W or placebo for 24 weeks of double-blind treatment. In this post-hoc analysis, we investigated the proportion of patients in SPIRIT-P1 and P2 studies who achieved 15% improvement in work productivity loss and 20% improvement in activity impairment domains of WPAI-SHP during double- blind treatment period. RESULTS: In SPIRIT-P1, at Week 24, 57.1% and 55.8% of biologic-naive patients on IXEQ4W and ADAQ2W respectively, achieved MCID estimates for work productivity loss compared to 25.6% of patients treated with placebo. The proportion of ixekizumab- and adalimumab-treated patients achieving MCIDs for activity impairment were significantly higher (IXEQ4W: p<0.001; ADAQ2W: p=0.001) com- pared to placebo-treated patients at Week 24. In SPIRIT-P2, significantly more TNFi-experienced patients on IXEQ4W (p<0.001) achieved MCIDs compared to placebo at Week 24. CONCLUSIONS: Treatment with ixekizumab was associated with clinically meaningful improvements in WPAI-SHP domains in biologic-naive and TNFi- experienced patients with active PsA.

The contribution of joint and skin improvements to the health-related quality of life of patients with psoriatic arthritis: a post hoc analysis of two randomised controlled studies.

OBJECTIVE: Determine the contribution of joint and skin improvements to health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). METHODS: SPIRIT-P1 and SPIRIT-P2 are phase 3 trials investigating ixekizumab, an interleukin-17A antagonist, in the treatment of patients with active PsA. Patients were randomised to ixekizumab or placebo. Outcomes included the Disease Activity Index for Psoriatic Arthritis (DAPSA), the Psoriasis Area and Severity Index (PASI), the European Quality of Life-Five Dimensions (EQ-5D) Visual Analogue Score (VAS), the 36-Item Short-Form Health Survey (SF-36) and the Work Productivity and Activity Impairment (WPAI) Questionnaire. The contribution of joint and skin improvements to HRQoL was modelled using a smoothing spline method and depicted with response surface graphics. RESULTS: In this integrated analysis, 402 patients with PsA had baseline psoriasis of ≥3% of body surface area. We applied response surface modelling to this patient data set to investigate the relationship between DAPSA, PASI and HRQoL improvements at week 24. The greatest improvement in EQ-5D VAS was associated with the largest per cent improvements in both DAPSA and PASI together, rather than DAPSA or PASI alone. Similar observations were made in domains of SF-36 and WPAI. CONCLUSION: Optimal improvements in patients' HRQoL were dependent on successful treatment of both joint and skin symptoms.

Ixekizumab improves patient-reported outcomes in patients with active psoriatic arthritis and inadequate response to tumour necrosis factor inhibitors: SPIRIT-P2 results to 52 weeks.

OBJECTIVES: To report patient-reported outcomes (PROs) of ixekizumab-treated patients with psoriatic arthritis (PsA) and an inadequate response (IR) or intolerance to tumour necrosis factor inhibitors (TNFi) to 52 weeks. METHODS: In SPIRIT-P2, patients with active PsA and an IR or intolerance to TNFi were randomised to ixekizumab 80 mg every 4 weeks (IXEQ4W; N=122) or every 2 weeks (IXEQ2W; N=123), or placebo (PBO; N=118) during the initial 24-week double-blind treatment period. At Week 16, background therapy was modified for IRs; additionally, IRs in the placebo group were re-randomised (1:1) to IXEQ2W or IXEQ4W. Patients receiving ixekizumab at Week 24 received the same dose during the study remainder. Patients completed several PROs for PsA disease activity, skin, health-related quality of life (HRQOL, and work through Week 52. RESULTS: Ixekizumab-treated patients reported significant improvements versus PBO in 36-Item Short Form Health Survey version 2, European Quality of Life 5 Dimensions visual analogue scale, Bath Ankylosing Spondylitis Disease Activity Index (total score and question 2), and Work Productivity and Activity Impairment Questionnaire-Specific Health Problem (3 of 4 domains) through Week 24. At Week 24, 9% (PBO), 52% (IXEQ4W), and 50% (IXEQ2W) of patients reported Dermatology Life Quality Index scores of 0 or 1; 0% (PBO) and 24% (IXEQ4W and IXEQ2W) reported Itch Numeric Rating Scale score of 0. Where data were collected, improvements persisted through Week 52. CONCLUSIONS: In patients with PsA and an IR or intolerance to TNFi, ixekizumab significantly improved disease activity, skin symptoms, HRQOL, and work productivity to 52 weeks.

Ixekizumab improves patient-reported outcomes up to 52 weeks in bDMARD-naïve patients with active psoriatic arthritis (SPIRIT-P1).

Objective: To report patient-reported outcomes of patients with PsA treated with ixekizumab up to 52 weeks. Methods: In SPIRIT-P1, biologic-naïve patients with active PsA were randomized to ixekizumab 80 mg every 4 weeks (IXEQ4W; N = 107) or every 2 weeks (IXEQ2W; N = 103) following a 160 mg starting dose, adalimumab 40 mg every 2 weeks (ADA; N = 101) or placebo (PBO; N = 106) during the initial 24-week double-blind treatment period. At week 24 (week 16 for inadequate responders), ADA (8-week washout before starting ixekizumab) and PBO patients were re-randomized to IXEQ2W or IXEQ4W. Patients receiving ixekizumab at week 24 received the same dose during the extension period (EP) to week 52. Patients completed measures including the Dermatology Life Quality Index (DLQI), Itch Numeric Rating Scale, 36-Item Short Form Health Survey version 2, European Quality of Life 5 Dimensions Visual Analogue Scale and Work Productivity and Activity Impairment Questionnaire-Specific Health Problem. Results: The IXEQ4W, IXEQ2W and ADA groups reported significant improvements in DLQI at week 24; 22% (PBO), 53% (IXEQ4W), 63% (IXEQ2W) and 54% (ADA) of patients reported DLQI scores of 0/1. The IXEQ4W, IXEQ2W and ADA groups reported significant improvements in Itch Numeric Rating Scale, 36-Item Short Form Health Survey version 2 physical component summary and some domain scores, and European Quality of Life 5 Dimensions Visual Analogue Scale at weeks 12 and 24; and in three of four Work Productivity and Activity Impairment Questionnaire-Specific Health Problem domains at week 24. Results are also presented through week 52 for the EP. Conclusion: In biologic-naïve patients with active PsA, ixekizumab significantly improved skin symptoms, health-related quality of life and work productivity. Trial Registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01695239; EU Clinical Trials Register, https://www.clinicaltrialsregister.eu, EudraCT2011-002326-49.

Sjögren's syndrome: managed care data from a large United States population highlight real-world health care burden and lack of treatment options.

OBJECTIVES: To better understand the real-world characteristics and costs of Sjögren's syndrome (SS). METHODS: Analysing the MarketScan Commercial Claims database from Jan. 1, 2006 to Dec. 31, 2011, we identified 10,414 patients ≥18 years old newly diagnosed with SS. Patient characteristics, drugs (commonly used for SS), resource utilisation, and medical costs were evaluated for 12 months pre- and post-diagnosis. RESULTS: Mean age was 55 years; 90% were female. At diagnosis, SS patients were most often seen by rheumatologists (39%) or internists (14.2%); the most common concurrent autoimmune conditions were rheumatoid arthritis (17.9%) and systemic lupus erythematosus (14.6%). Other common comorbidities were hypertension (37.6%), osteoarthritis (31.4%), and hyperlipidaemia/dyslipidaemia (30.3%). Post diagnosis of SS, claims for myocardial infarction and coronary artery bypass graft doubled. Medications of interest prescribed post-diagnosis were eye/mouth drugs (32.2%) and synthetic immunosuppressants (32.1%). Biologic drugs were prescribed to a minority (TNF inhibitors, ~5.0%; non-TNF inhibitors, 1%). Of note, prescriptions for all systemic immunotherapies (synthetic and biologic) were significantly lower in the subgroup without concurrent autoimmune disease, and 15.1% of the overall population had no SS-related prescriptions. Post diagnosis, total medical resource utilisation and total medical costs increased (1.2 and 1.4-fold, respectively). CONCLUSIONS: In this retrospective, real-world analysis, medical claims in the first year after SS diagnosis revealed that cardiovascular (CV) events increased and all-cause healthcare costs grew by 40%. Pharmacologic management consisted primarily of low potency immunomodulation and symptomatic treatments. Systemic disease-modifying therapies were used mostly in patients who had another concurrent autoimmune disease, suggesting a lack of treatment options for SS.

Patterns of statin initiation, intensification, and maximization among patients hospitalized with an acute myocardial infarction.

BACKGROUND: Intensive statins are superior to moderate statins in reducing morbidity and mortality after an acute myocardial infarction. Although studies have documented rates of statin prescription as a quality performance measure, variations in hospitals' rates of initiating, intensifying, and maximizing statin therapy after acute myocardial infarction are unknown. METHODS AND RESULTS: We assessed statin use at admission and discharge among 4340 acute myocardial infarction patients from 24 US hospitals (2005-2008). Hierarchical models estimated site variation in statin initiation in naïve patients, intensification in those undergoing submaximal therapy, and discharge on maximal therapy (defined as a statin with expected low-density lipoprotein cholesterol lowering ≥ 50%) after adjustment for patient factors, including low-density lipoprotein cholesterol level. Site variation was explored with a median rate ratio, which estimates the relative difference in risk ratios of 2 hypothetically identical patients at 2 different hospitals. Among statin-naïve patients, 87% without a contraindication were prescribed a statin, with no variability across sites (median rate ratio, 1.02). Among patients who arrived on submaximal statins, 26% had their statin therapy intensified, with modest site variability (median rate ratio, 1.47). Among all patients without a contraindication, 23% were discharged on maximal statin therapy, with substantial hospital variability (median rate ratio, 2.79). CONCLUSIONS: In a large, multicenter acute myocardial infarction cohort, statin therapy was begun in nearly 90% of patients during hospitalization, with no variability across sites; however, rates of statin intensification and maximization were low and varied substantially across hospitals. Given that more intense statin therapy is associated with better outcomes, changing the existing performance measures to include the intensity of statin therapy may improve care.

Changes in low-density lipoprotein cholesterol levels after discharge for acute myocardial infarction in a real-world patient population.

Aggressively managing low-density lipoprotein cholesterol (LDL-C) after myocardial infarction (MI) is a cornerstone of secondary prevention. The changes in LDL-C after MI and the factors associated with LDL-C levels are unknown. Therefore, we directly measured fasting LDL-C levels in 797 MI patients from 24 US hospitals from 2005 to 2008. Mean LDL-C levels at discharge, 1 month, and 6 months were 95.1, 81.9, and 87.1 mg/dL, respectively. In a hierarchical, multivariable, repeated measures model, older age, male sex, and hypertension were associated with lower LDL-C levels, whereas self-reported avoidance of health care because of cost was associated with higher LDL-C. Both the presence and intensity of statin therapy at discharge were strongly associated with LDL-C levels, with adjusted mean 6-month changes of -3.4 mg/dL (95% confidence interval (CI): -12.1, 5.3) for no statins; 1.7 mg/dL (95% CI: -4.7, 8.1) for low statins; -10.2 mg/dL (95% CI: -14.5, -6.0) for moderate statins; and -13.9 mg/dL (95% CI: -19.7, -8.0) for intensive statins (P < 0.001). In conclusion, we found that greater reductions in LDL-C levels after MI were strongly associated with the presence and intensity of statin therapy, older age, male sex, hypertension, and better socioeconomic status. These findings support the use of intensive statin therapy in post-MI patients and provide estimates of the expected LDL-C changes after MI in a real-world population.

Filling the "GAP" in Real-World Assessment of Psoriatic Arthritis Disease Activity: Performance Characteristics of a Global/Pain Composite Endpoint.

INTRODUCTION: Some retrospective data sources, such as electronic health records in the USA, report composite outcome measures not fully validated in psoriatic arthritis (PsA). However, they often contain global assessments, such as a Physician Global Assessment (PhGA) and Patient Global Assessment (PatGA), along with patient-reported pain scores, which individually are considered validated in PsA. This research described the performance characteristics of a 3-item global assessment and pain (GAP) composite endpoint using data from the ixekizumab phase 3 PsA clinical trial program. METHODS: Discrimination of GAP was assessed by comparing placebo to active treatment arms. The magnitude of treatment effect and responsiveness were compared to Disease Activity Index for PsA (DAPSA), clinical DAPSA, DAPSA28, and Psoriatic Arthritis Disease Activity Score (PASDAS) using effect size (ES) and standardized response mean (SRM), respectively. Construct validity was evaluated through correlation among the composite endpoints, and with other physician- and patient-reported outcomes. Change in GAP was compared in patients who reached low disease activity (LDA) levels based on DAPSA, cDAPSA, and PASDAS vs those who did not. RESULTS: GAP discriminated between active treatment and placebo with statistically significant separation as early as week 1. The largest ES/SRM was seen with GAP (2.29/1.74) and PASDAS (2.47/1.68). GAP had the strongest correlation with PASDAS (0.81-0.92) and showed moderate correlations with patient-assessed physical function, low correlations with physician-assessed skin and nail psoriasis, and low to moderate correlation with physician-assessed enthesitis. A significantly greater improvement in GAP was seen in the groups achieving LDA states compared to those not (p < 0.001). CONCLUSION: The GAP composite, an abbreviated endpoint comprising measures common in electronic health records, has promising performance characteristics and could be used to address important clinical questions regarding outcomes and impact of PsA in existing datasets. CLINTRIALS. GOV IDENTIFIER: NCT01695239; NCT02349295.

When doctors are assessing patients with psoriatic arthritis in clinical trials, they use tools, which include questions that patients answer and questions that doctors answer, in addition to a physical exam, to help evaluate how patients are doing. In a routine clinical practice setting, all of these same tools may not be used because they take a longer time to document information during a patient office visit. The goals of this research were to (1) create a new tool, which uses questions that patients and doctors answer, to help doctors evaluate how patients with psoriatic arthritis are doing in routine clinical practice, and (2) to assess if this new tool works as well as older tools. The new tool has fewer questions for the doctor and patient to answer and may take less time to document information but may result in some symptoms that patients experience not being regularly assessed. Data from clinical trials were used to compare the new tool to older tools to evaluate if doctors are able to assess psoriatic arthritis the same way. The results of the study showed that doctors are able to assess patients with psoriatic arthritis similarly with the new tool compared to older tools. This information will increase awareness of the new tool and could make it easier for doctors to evaluate patients with psoriatic arthritis in routine clinical practice.

Real-World Treatment Patterns, Clinical Outcomes, and Symptom Burden in Patients With Psoriatic Arthritis Prescribed Ixekizumab in the United States.

OBJECTIVE: The objective of this study was to describe the real-world characteristics and clinical status of patients with psoriatic arthritis (PsA) currently prescribed ixekizumab. METHODS: Data were drawn from the Adelphi PsA Plus Disease Specific Programme (DSP), a cross-sectional survey conducted in the United States between September 2021 and March 2022. Rheumatologists provided data for their next five consulting patients currently receiving ixekizumab, including demographic and clinical characteristics, disease severity, treatment history, reasons for treatment choice, satisfaction with current treatment, and current and historic symptom burden. Patients voluntarily completed questionnaires, providing perceptional data on symptom burden and satisfaction with current treatment. RESULTS: Overall, 68 rheumatologists provided data on 275 patients with PsA, 90 of whom completed the voluntary questionnaire. Patients had been prescribed ixekizumab for a mean of 11.7 (SD 10.6) months. Clinical characteristics, disease severity, and symptom burden of patients with PsA improved significantly from ixekizumab initiation to the most recent consultation, including symptom burden, tender and swollen joint counts, and body surface area affected by psoriasis (all P < 0.001). Both rheumatologists and patients were satisfied with ixekizumab treatment and reported improvements in pain and fatigue. Improvements were noted after more than three months of ixekizumab treatment duration and regardless of whether the patients had prior exposure to an advanced therapy or were treatment naïve. CONCLUSION: Our results indicate that ixekizumab was efficacious in the treatment of PsA in real-world clinical practice, complementing efficacy data from randomized controlled clinical trials. The results of this study may assist rheumatologists and their patients in making informed treatment choices.

Satisfaction with the Injection Experience of a New, Citrate-Free Formulation of Ixekizumab.

INTRODUCTION: A new, citrate-free ixekizumab formulation, which is bioequivalent to the original formulation, was associated with significant reduction in injection site pain. This study evaluates patient satisfaction with the first injection experience of citrate-free ixekizumab in a real-world setting. METHODS: A non-interventional, observational, web-based survey of adults (≥ 18 years) with psoriasis, psoriatic arthritis, or axial spondyloarthritis was conducted between August 2022 and March 2023. Patients enrolled in the Taltz US Customer Support Program were identified as receiving either the original ixekizumab or initiating citrate-free ixekizumab. Patients receiving original ixekizumab completed one survey at baseline to assess satisfaction with the formulation and one survey after switching to assess satisfaction, willingness to continue using and recommending citrate-free ixekizumab, and formulation preference. Participants previously exposed to ixekizumab completed one survey to assess their satisfaction and willingness to continue using and recommending citrate-free ixekizumab. Descriptive and comparative statistics are reported for patients that switched from original to citrate-free ixekizumab (n = 361); and descriptive statistics are reported for patients not previously exposed to ixekizumab (n = 90). RESULTS: A total of 451 patients were included in the analysis. Significantly more patients were satisfied with their first injection with citrate-free ixekizumab compared to original ixekizumab (83.9% vs. 71.7% respectively; p = 0.0001). Almost all patients who switched from original ixekizumab were definitely or mostly willing to continue using and recommending citrate-free ixekizumab (93.9% and 93.4%, respectively). Additionally, 94.2% of patients who switched from original to citrate-free ixekizumab preferred citrate-free ixekizumab or had no preference. Three-fourths of patients not previously exposed to ixekizumab were satisfied with their first injection with citrate-free ixekizumab and 94.5% were definitely or mostly willing to continue using citrate-free ixekizumab. CONCLUSION: The citrate-free ixekizumab formulation was preferred and well accepted by most patients who switched from the original ixekizumab formulation. Similar findings were seen for those newly initiating citrate-free ixekizumab.

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.

Relationship between financial impact and coverage of drugs in Australia.

OBJECTIVES: The aim of this study was to estimate the relationship between the financial impact of a new drug and the recommendation for reimbursement by the Australian Pharmaceutical Benefits Advisory Committee (PBAC). METHODS: Data in the PBAC summary database were abstracted for decisions made between July 2005 and November 2009. Financial impact-the upper bound of the values presented in the PBAC summary database-was categorized as ≤A$0, >A$0 up to A$10 million, A$10 million up to A$30 million, and >A$30 million per year. Descriptive, logistic, survival, and recursive partitioning decision analyses were used to estimate the relationship between the financial impact of a new drug indication and the recommendation for reimbursement. Multivariable analyses controlled for other clinical and economic variables, including cost per quality-adjusted life-year gained. RESULTS: Financial impact was a significant predictor of the recommendation for reimbursement. In the logistic analysis, the odds ratios of reimbursement for drug submissions with financial impacts ≥A$10 million to ≥A$30 million or >A$0 to

Changes in musculoskeletal disease activity and patient-reported outcomes in patients with psoriatic arthritis treated with ixekizumab: results from a real-world US cohort.

Introduction: Ixekizumab has demonstrated efficacy in pivotal trials in patients with psoriatic arthritis (PsA), both those naïve to prior biologic therapy and those with prior inadequate response or intolerance to biologics; however, minimal information is currently available on the effectiveness of ixekizumab in routine clinical practice. The objective of this study was to investigate the clinical effectiveness of ixekizumab for the treatment of PsA over 6- and 12-month follow-up periods in a real-world setting. Methods: This retrospective cohort study included patients who initiated treatment with ixekizumab from the OM1 PremiOMTM PsA dataset, a dataset of over 50,000 patients with claims and electronic medical record (EMR) data. Changes in musculoskeletal outcomes, such as tender and swollen joint count and patient-reported pain, as well as physician and patient global assessment, as measured using the Clinical Disease Activity Index (CDAI), and Routine Assessment of Patient Index Data 3 (RAPID3) were summarized at 6 and 12 months. The RAPID3, CDAI score, and their individual components were assessed in multivariable regressions adjusting for age, sex, and baseline value. The results were stratified by biologic disease-modifying antirheumatic drug (bDMARD) status (naïve vs. experienced) and monotherapy status (monotherapy vs. combination therapy with conventional synthetic DMARDs). Changes in a 3-item composite score derived from a physician global assessment, patient global assessment, and patient-reported pain score were summarized. Results: Among the 1,812 patients identified receiving ixekizumab, 84% had prior bDMARD treatment and 82% were monotherapy users. All outcomes improved at 6 and 12 months. For RAPID3, the mean (SD) change at 6 and 12 months was -1.2 (5.5) and -1.2 (5.9), respectively. Patients overall, bDMARD experienced, and monotherapy patients achieved statistically significant mean change in CDAI and all components from baseline to 6 and 12 months in adjusted analyses. Patients experienced an improvement in the 3-item composite score at both time points. Conclusion: Treatment with ixekizumab was associated with improvements in musculoskeletal disease activity and PROs as assessed by several outcome measures. Future research should assess ixekizumab's clinical effectiveness in the real world across all PsA domains using PsA-specific endpoints.

Treatment patterns in paediatric and adult patients with SLE: a retrospective claims database study in the USA.

OBJECTIVE: To assess real-world treatment regimens and patterns in childhood-onset SLE (cSLE) and adult-onset SLE (aSLE) cohorts, including similarities in treatments, duration of use and adherence. METHODS: This retrospective study utilised data from Merative L.P. MarketScan Research Databases (USA). Index date was the date of first SLE diagnosis (2010-2019). Patients aged <18 years (cSLE) and ≥18 years (aSLE) at index date with confirmed SLE diagnosis and ≥12 months continuous enrolment during pre-index and post-index periods were included. The cohorts were stratified based on the presence (existing) or absence (new) of pre-index SLE. Primary outcomes (post-index period) included treatment regimens (all patients), and adherence (proportion of days covered (PDC)) and discontinuation of therapies initiated within 90 days of diagnosis (new patients). Univariate comparisons between cSLE and aSLE cohorts were performed using Wilcoxon rank-sum and χ2 (or Fisher's exact) tests. RESULTS: cSLE cohort included 1275 patients (mean age=14.1 years) and aSLE cohort included 66 326 patients (mean age=49.7 years). Antimalarials and glucocorticoids were commonly used among new (cSLE=64.4%/62.0%; aSLE=51.8%/49.7%) and existing (cSLE=68.6%/58.9%; aSLE=63.8%/51.3%) patients in both cohorts. Median oral glucocorticoid dose (prednisone equivalent) was higher in cSLE vs aSLE (new=22.1 vs 14.0 mg/day; existing=14.4 vs 12.3 mg/day; p<0.05). Mycophenolate mofetil use was higher in patients with cSLE vs aSLE (new=26.2% vs 5.8%; existing=37.6% vs 11.0%; p<0.0001). Compared with aSLE, more patients used combination therapies in cSLE (p<0.0001). Median PDC was higher in cSLE vs aSLE for antimalarials (0.9 vs 0.8; p<0.0001) and oral glucocorticoids (0.6 vs 0.3; p<0.0001). Treatment discontinuation was lower in cSLE vs aSLE for antimalarials (25.0% vs 33.1%; p<0.0001) and oral glucocorticoids (56.6% vs 71.2%; p<0.0001). CONCLUSIONS: Management of cSLE and aSLE includes the same medication classes; differences include more intensive use of therapy in cSLE, warranting the need for approved safe medications for cSLE.

Real-world treatment patterns and use of adjunctive pain and anti-inflammatory medications among patients with psoriatic arthritis treated with IL-17A inhibitors in the United States.

BACKGROUND: Much of the current research on treatment patterns and use of adjunctive pain and anti-inflammatory medications among patients living with psoriatic arthritis (PsA) predates the approval and uptake of IL (interleukin)-17A inhibitors. OBJECTIVE: To compare real-world treatment patterns and use of adjunctive pain and antiinflammatory medications between patients with PsA initiating the IL-17A inhibitors, ixekizumab and secukinumab, in a US-managed care population. METHODS: We conducted a retrospective cohort study using the HealthCore Integrated Research Database. Patients with a PsA diagnosis who initiated ixekizumab or secukinumab treatment between December 1, 2017, and November 30, 2019, were identified. Two cohorts were created based on which of the 2 medications was initiated (index date), and patients with prior use of either drug were excluded, as were patients with ankylosing spondylitis. Patients had to be continuously enrolled in the health plan for 6 months prior to (baseline) and 12 months after the index date (post-index). Inverse probability of treatment weighting was used to minimize confounding from baseline demographic and clinical differences between cohorts. Treatment patterns (dosing, persistence, discontinuation, and switching) and use of adjunctive pain/anti-inflammatory medications were assessed and compared between weighted cohorts using chi-square and t-tests. RESULTS: In total, 407 patients were identified in the ixekizumab cohort (mean age 51.6 years; 54% female) and 1,508 patients were identified in the secukinumab cohort (mean age 50.1 years; 59% female). Prior to weighting, presence of a psoriasis diagnosis code (ixekizumab: 60% vs secukinumab: 45%; standardized difference [std diff] = -0.30), specialty of the index prescriber (std diff = 0.38), and mean number of prior advanced therapies (2.0 vs 1.5; std diff = -0.33) were different between cohorts. Cohorts were well balanced after weighting. The majority of secukinumab patients (71%) received an index dose of 300 mg. Rates of persistence (ixekizumab: 40% vs secukinumab: 43%; P = 0.411) and switching (25% vs 20%; P = 0.072) were not statistically different between cohorts. Use of new adjunctive pain and anti-inflammatory medications was not statistically different between cohorts either (ixekizumab: 63% vs secukinumab: 58%; P = 0.187). CONCLUSIONS: Real-world treatment patterns and use of adjunctive pain and anti-inflammatory medications were similar in patients with PsA initiating ixekizumab and secukinumab in this US-managed care population. Further research examining reasons for discontinuation, switching, and use of adjunctive medications may help inform treatment decisions for patients living with PsA. DISCLOSURES: Ms Pizzicato, Ms Ketkar, and Dr Grabner are employees of HealthCore, Inc, which received funding from Eli Lilly and Company for the conduct of the study on which this manuscript is based. Ms Pepe was an employee of HealthCore, Inc., during the time the study was conducted. Dr Grabner is a shareholder of Elevance Health (legacy Anthem, Inc.). Dr Vadhariya, Dr Birt, and Ms Bolce are employees of Eli Lilly and Company, the manufacturer of ixekizumab (Taltz). Dr Birt and Ms Bolce are shareholders of Eli Lilly and Company. Dr Walsh is a paid consultant to Eli Lilly and Company and Novartis, the manufacturers of ixekizumab (Taltz) and secukinumab (Cosentyx), respectively. Additionally, Dr Walsh is a paid consultant for Pfizer, Janssen, AbbVie, and UCB and has contracts with Pfizer, AbbVie, and Merck.

Cellular and molecular basis for endometriosis-associated infertility.

Endometriosis is a gynecological disease characterized by the presence of endometrial glandular epithelial and stromal cells growing in the extra-uterine environment. The disease afflicts 10%-15% of menstruating women causing debilitating pain and infertility. Endometriosis appears to affect every part of a woman's reproductive system including ovarian function, oocyte quality, embryo development and implantation, uterine function and the endocrine system choreographing the reproductive process and results in infertility or spontaneous pregnancy loss. Current treatments are laden with menopausal-like side effects and many cause cessation or chemical alteration of the reproductive cycle, neither of which is conducive to achieving a pregnancy. However, despite the prevalence, physical and psychological tolls and health care costs, a cure for endometriosis has not yet been found. We hypothesize that endometriosis causes infertility via multifaceted mechanisms that are intricately interwoven thereby contributing to our lack of understanding of this disease process. Identifying and understanding the cellular and molecular mechanisms responsible for endometriosis-associated infertility might help unravel the confounding multiplicities of infertility and provide insights into novel therapeutic approaches and potentially curative treatments for endometriosis.