Pfizer (Switzerland)

Due to the multisystemic nature of sickle cell disease (SCD), complications can occur together and thus discerning costs associated with individual complications requires a methodology that can estimate the costs of a given complication while accounting for the presence of other complications. In this study, we aimed to estimate period-based incremental costs associated with specific chronic complications in patients with SCD in England while accounting for multimorbidity. All-cause primary and secondary care healthcare resource utilisation (HCRU) was obtained for a retrospective cohort of patients with SCD using Clinical Practice Research Datalink (CPRD) Aurum linked to Hospital Episode Statistics (HES) datasets. Annualised HCRU and costs were calculated, dividing patient-level events by patient-level time (in years) to obtain per person per year estimates. A series of generalised linear models were used with adjustment for demographic factors and proportion of follow-up time with each complication to estimate the costs associated with 10 chronic SCD-related complications of interest. For these costs, annual equivalent costs can be obtained by dividing by the median follow-up time of 4.74 years. Patients with a diagnosis of SCD, with or without complications, in CPRD or HES with at least 12 months follow-up. Period-based all-cause direct healthcare costs. Of the 1271 patients with SCD included in the study, 49.9% (n=634) had at least one complication and of these 41.3% (n=262) had two or more complications either at baseline or during follow-up. Patients with complications had higher all-cause healthcare costs compared with patients without complications (mean (SD) annualised cost £16 058 (£21 488) vs £4399 (£6635)). Patients with complications had four times the number of annualised inpatient admissions (6.1 vs 1.5 admissions) and more than double the number of annualised bed days in hospital (8.3 vs 3.8 days) over a median 4.74 years of follow-up. Of the complications evaluated, end-stage renal disease had the highest estimated incremental cost of £252 083 (95% CI £214 478 to £283 745) over 4.74 years; this is in addition to the £18 547 period-based cost among patients with SCD without complications. Osteonecrosis was the most common complication with an estimated incremental cost of £27 399 (95% CI £6417 to £43 319) over the same period. Estimating the cost of complications, while accounting for multimorbidity, is essential to determine the true direct cost of SCD. The modelling method presented in our study provides period-based estimates of cost and hospital admissions for individual complications in patients with SCD, accounting for multimorbidity. This approach can be used and extended to other diseases with multisystemic complications to estimate the direct HCRU and costs of individual complications.

ObjectiveBothersome ulcerative colitis (UC) symptoms include stool frequency (SF), rectal bleeding (RB), abdominal pain and bowel urgency; symptomatic relief is a key treatment goal. Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active UC. We assessed outcomes related to symptomatic relief among patients with moderately to severely active UC in the phase III ELEVATE UC clinical programme.MethodsIn both ELEVATE UC 52 and ELEVATE UC 12, adults were randomly assigned (2:1) to etrasimod 2 mg QD or placebo. Symptomatic remission, symptomatic response, complete symptomatic remission, SF and RB were evaluated at each trial visit. Bowel urgency and abdominal pain were also assessed (weeks 12 and 52).ResultsSignificantly more patients receiving etrasimod were in symptomatic remission and symptomatic response at weeks 12 and 52 versus placebo (all p<0.001). Improvements from baseline in RB and SF subscores were significantly greater in those receiving etrasimod versus placebo from weeks 2 (ELEVATE UC 12) and 4 (ELEVATE UC 52). Similarly, a significantly greater number of patients in the etrasimod versus placebo group were in complete symptomatic remission. At weeks 12 and 52, the number of patients achieving clinically meaningful improvements in bowel urgency, bowel urgency remission and abdominal pain remission was significantly greater for etrasimod versus placebo (all p<0.05).ConclusionEtrasimod was efficacious in improving symptoms of UC from week 2; improvements were maintained through week 52.Trial registration numberClinicalTrials.gov: NCT03945188; NCT03996369.

Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). However, its efficacy, safety, and the appropriate dosage have not been extensively investigated in the Japanese population. This phase 2, multicenter, randomized, double-blind, placebo-controlled dose-ranging, 12-week trial was carried out among Japanese patients with moderately to severely active UC. Patients were randomized 1:1:1 to receive etrasimod 1 mg once daily (QD), etrasimod 2 mg QD, or placebo. The primary efficacy endpoint was the proportion of patients achieving clinical remission at week 12. Secondary efficacy endpoints and treatmentemergent adverse events (TEAEs) were also investigated. Efficacy endpoints were presented as proportions of patients achieving each outcome. Overall, 17, 19, and 18 patients received etrasimod 1 mg QD, etrasimod 2 mg QD, and placebo, respectively. One patient receiving etrasimod 1 mg (6.7%), 5 patients receiving etrasimod 2 mg (26.3%), and no patients receiving placebo (0%) achieved clinical remission. More patients receiving etrasimod versus placebo achieved secondary endpoints, except endoscopic normalization, at week 12. TEAEs were experienced by 9 patients receiving etrasimod 1 mg (52.9%), 13 patients receiving etrasimod 2 mg (68.4%), and 10 patients receiving placebo (55.6%). None of the TEAEs were serious and none experienced by patients receiving etrasimod led to treatment discontinuation. Overall, etrasimod 2 mg QD for up to 12 weeks appeared efficacious and safe in these Japanese patients with moderately to severely active UC. All TEAEs were mild to moderate in severity. (ClinicalTrials.gov: NCT05061446).

Abstract Background There is an unmet need for novel advanced therapies for patients with mildly to moderately active ulcerative colitis (UC), who are most frequently treated with aminosalicylates, steroids and thiopurines. Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC. This post hoc analysis evaluated the efficacy and safety of etrasimod 2 mg QD vs placebo in a subpopulation of patients from the ELEVATE UC clinical programme with mildly to moderately active UC at baseline, defined as a modified Mayo score (MMS) of 4–6. Methods Data were pooled from the phase 3, randomised, global ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials, and the ELEVATE UC 40 JAPAN (NCT04706793) trial.1,2 This analysis included a subset of the pooled patient population aged ≥18 years who had a baseline MMS of 4–6, including a centrally read endoscopic subscore ≥2 and a rectal bleeding subscore (RBS) ≥1. Efficacy endpoints at Week 12 and Week 52 included clinical remission, endoscopic improvement, symptomatic remission and histologic endoscopic mucosal improvement; at Week 52, sustained clinical remission and corticosteroid (CS)-free clinical remission were assessed. Least squares mean change from baseline in patient-reported outcome 2 (PRO2) score (sum of RBS and stool frequency subscores) was assessed at each visit up to Week 52. Proportions of patients with treatment-emergent adverse events (TEAEs), serious TEAEs and TEAEs leading to discontinuation were assessed. Results In this subgroup analysis, 221 received etrasimod and 109 received placebo. Baseline characteristics were generally balanced between treatment groups; 95 (28.8%) patients were receiving CS at baseline and 241 (73.0%) were biologic/Janus kinase inhibitor naïve. Median baseline MMS was 6.0 in both treatment groups. Significantly greater proportions of patients receiving etrasimod vs placebo achieved all efficacy endpoints at Week 12 and Week 52 (Figure). A significant decrease in PRO2 score for etrasimod vs placebo was observed as early as Week 2 and continued through to Week 32; numerically greater score decreases were observed from Week 36 to Week 52 (Table). Safety was similar between the etrasimod and placebo groups, and consistent with the overall ELEVATE UC population.1 Conclusion Etrasimod demonstrated robust efficacy in clinical, symptomatic and endoscopic endpoints and safety consistent with the overall population in patients with mildly to moderately active UC, as defined by an MMS of 4–6.

BackgroundEtrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Here, we evaluate the impact of etrasimod 2 mg QD on health-related quality of life (HRQoL) in patients with UC.MethodsThis post hoc analysis used data from the Phase 3 randomized controlled trials, ELEVATE UC 52 and ELEVATE UC 12. HRQoL measures included: Inflammatory Bowel Disease Questionnaire (IBDQ), 36-Item Short Form Survey (SF-36), and Work Productivity and Activity Impairment Questionnaire: Ulcerative Colitis (WPAI:UC) completed at baseline, Week 12 (both trials), and Week 52 (ELEVATE UC 52 only). For IBDQ analyses, patients were stratified by prior exposure to biologics/Janus kinase inhibitors (JAKi) and baseline modified Mayo score (MMS; 4-6 or 7-9).ResultsGenerally, significantly greater proportions of patients receiving etrasimod (N = 527) vs placebo (N = 260) achieved IBDQ remission (IBDQ total score ≥170) and IBDQ response (IBDQ total score increase from baseline ≥16), with significant improvement in all IBDQ domain scores at Week 12 and maintained through Week 52. Significant differences in IBDQ remission and IBDQ response rates between etrasimod and placebo were more consistent among biologic/JAKi-naive patients vs those who were biologic/JAKi-experienced and in those with baseline MMS 7-9 vs 4-6. Significant improvements were observed in several SF-36 domain and summary scores and WPAI:UC domain scores at Week 12 and Week 52.ConclusionsEtrasimod 2 mg QD demonstrated significant and clinically meaningful improvements across multiple HRQoL measures, including WPAI, vs placebo.Clinical Trial RegistrationClinicalTrials.gov: NCT03945188; NCT03996369

BackgroundEtrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). This post hoc analysis reports the efficacy and safety of etrasimod based on baseline corticosteroid (CS) use in the ELEVATE UC clinical program.MethodsPatients with UC received etrasimod 2 mg or placebo for up to 52 weeks. CS use was permitted; tapering was recommended from Week 12. Efficacy was assessed at Weeks 12 and 52 in ELEVATE UC 52, and Week 12 in ELEVATE UC 12, for patients in the CS and no-CS subgroups. CS-free efficacy at Week 52 was assessed in patients with baseline CS use.ResultsIn ELEVATE UC 52 and ELEVATE UC 12, 93 of 289 (32.2%) and 65 of 238 (27.3%) patients receiving etrasimod and 42 of 144 (29.2%) and 34 of 116 (29.3%) patients receiving placebo, respectively, had concomitant CS use at baseline. In the CS and no-CS subgroups, higher proportions of patients who received etrasimod vs placebo achieved clinical remission (p < 0.05) in ELEVATE UC 52 at Week 12 (CS: 32.3% vs 16.7%; no-CS: 26.0% vs 4.9%) and Week 52 (CS: 31.2% vs 9.5%; no-CS: 33.2% vs 6.9%). In the CS subgroup, significantly more patients receiving etrasimod achieved CS-free clinical remission at Week 52 (31.2% vs 7.1%) compared with those receiving placebo. No increases in infection rates were observed with baseline CS use. Safety was comparable between subgroups.ConclusionsEtrasimod demonstrated efficacy in inducing and maintaining remission in both subgroups. CS-free remission was achieved in the CS subgroup. Safety was consistent, with no increase in infections.Clinical Trial IdentifiersNCT03945188; NCT03996369.

BackgroundBiomarkers offer potential alternatives to endoscopies in monitoring ulcerative colitis (UC) progression and therapeutic response. This post hoc analysis of the ELEVATE UC clinical program assessed potential predictive values of fecal calprotectin (fCAL) and high-sensitivity C-reactive protein (hsCRP) as biomarkers and associated responses to etrasimod, an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC, in 2 phase 3 clinical trials.MethodsIn ELEVATE UC 52 and ELEVATE UC 12, patients were randomized 2:1 to 2 mg of etrasimod once daily or placebo for 52 or 12 weeks, respectively. Fecal calprotectin/hsCRP differences between responders and nonresponders for efficacy end points (clinical remission, clinical response, endoscopic improvement-histologic remission [EIHR]) were assessed by Wilcoxon P-values. Sensitivity and specificity were presented as receiver operating characteristics (ROC) curves with area under the curve (AUC).ResultsIn ELEVATE UC 52 and ELEVATE UC 12, 289 and 238 patients received etrasimod and 144 and 116 received placebo, respectively. Baseline fCAL/hsCRP concentrations were generally balanced. Both trials had lower week-12 median fCAL levels in week-12 responders vs nonresponders receiving etrasimod for clinical remission, clinical response, and EIHR (all P < .001), with similar trends for hsCRP levels (all P < .01). For etrasimod, AUCs for fCAL/hsCRP and EIHR were 0.85/0.74 (week 12; ELEVATE UC 52), 0.83/0.69 (week 52; ELEVATE UC 52), and 0.80/0.65 (week 12; ELEVATE UC 12).ConclusionsFecal calprotectin/hsCRP levels decreased with etrasimod treatment; ROC analyses indicated a prognostic correlation between fCAL changes during induction and short-/long-term treatment response.

Introduction: Etrasimod is an investigational, oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator in development for the treatment of moderately to severely active ulcerative colitis (UC). Prior analyses demonstrated etrasimod efficacy in UC1 and greater improvement from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score and domains vs placebo (PBO).2 Methods: This post hoc subgroup analysis examined the effect of prior and concomitant therapies on IBDQ scores in the phase 3 ELEVATE UC clinical program. In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), eligible patients (pts) with modified Mayo scores of 4–9 completed the 32-item IBDQ at Weeks (Wks)12 (both trials) and 52 (ELEVATE UC 52). In this analysis, pts were stratified by prior biologic/Janus kinase inhibitor (bio/JAKi) and baseline corticosteroid (CS) use. Least squares (LS) mean change from baseline in IBDQ total and domain scores were compared for etrasimod vs PBO (data as observed). Proportions of pts with IBDQ remission (total score ≥ 170) were analyzed (nonresponder imputation). Results: Among all randomized patients, there were 304/433 and 236/354 pts without prior bio/JAKi use and 298/433 and 255/354 pts without baseline CS use in ELEVATE UC 52 and ELEVATE UC 12, respectively. Overall, mean baseline IBDQ total scores were similar in pts with and without prior bio/JAKi or baseline CS use. At Wks12 (both trials) and 52 (ELEVATE UC 52), LS mean change from baseline in IBDQ total and domain scores was higher (p < 0.05) for etrasimod vs PBO in pts without prior bio/JAKi and pts without baseline CS use (Table 1). IBDQ remission was generally achieved by significantly higher proportions of pts receiving etrasimod vs PBO regardless of prior bio/JAKi or baseline CS use at Wk52 (prior bio/JAKi use: No, 46.8% vs 21.2% [p < 0.001] and Yes, 25.0% vs 11.1% [P=0.043]; baseline CS use: No, 41.3% vs 15.7% [p < 0.001] and Yes, 38.7% vs 23.8% [P=0.087]). Conclusion: Pts receiving etrasimod had improvements in IBDQ total score and in all 4 domains at Wk12, maintained at Wk52. Significant differences were shown in these outcomes with etrasimod vs PBO in pts without prior bio/JAKi and without baseline CS use. IBDQ remission was generally achieved by higher proportions of pts without vs with prior bio/JAKi or without vs with baseline CS use.