Background: Patient-reported outcomes (PROs) are important when evaluating treatment benefits in rheumatoid arthritis (RA). We compared upadacitinib, an oral, selective JAK-1 inhibitor, with placebo to assess clinically meaningful improvements in PROs in patients with RA who have had inadequate responses to biologic disease-modifying antirheumatic drugs (bDMARD-IR). Methods: PRO responses between upadacitinib 15 mg or 30 mg and placebo were evaluated at week 12 from the SELECT-BEYOND trial. Improvement was determined by measuring Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire Disability Index (HAQ-DI), Short Form-36 Health Survey (SF-36), duration and severity of morning (AM) stiffness, and Insomnia Severity Index (ISI). Least squares mean changes and percentage of patients reporting improvements ≥ minimum clinically important differences (MCID) and scores greater than or equal to normative values were determined. The number needed to treat (NNT) to achieve clinically meaningful improvements was calculated. Results: In 498 patients, both upadacitinib doses resulted in statistically significant changes from baseline versus placebo in PtGA, pain, HAQ-DI, SF-36 Physical Component Summary (PCS), 7 of 8 SF-36 domains (15 mg), 6 of 8 SF-36 domains (30 mg), and AM stiffness duration and severity. Compared with placebo, more upadacitinib-treated patients reported improvements ≥ MCID in PtGA, pain, HAQ-DI, SF-36 PCS, 7 of 8 SF-36 domains (15 mg), 5 of 8 SF-36 domains (30 mg), AM stiffness duration and severity, and ISI (30 mg) and scores ≥ normative values in HAQ-DI and SF-36 domains. Across most PROs, NNTs to achieve MCID with upadacitinib ranged from 4 to 7 patients. Conclusions: In bDMARD-IR RA patients, upadacitinib (15 mg or 30 mg) improved multiple aspects of quality of life, and more patients reached clinically meaningful improvements approaching normative values compared with placebo. Trial registration: The trial is registered with ClinicalTrials.gov (NCT02706847), registered 6 March 2016.

Background: In previous clinical trials, patients with active rheumatoid arthritis (RA) treated with upadacitinib (UPA) have improved patient-reported outcomes (PROs). This post hoc analysis of SELECT-CHOICE, a phase 3 clinical trial, evaluated the impact of UPA vs abatacept (ABA) with background conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on PROs in patients with RA with inadequate response or intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR). Methods: Patients in SELECT-CHOICE received UPA (oral 15 mg/day) or ABA (intravenous). PROs evaluated included Patient Global Assessment of Disease Activity (PtGA) by visual analog scale (VAS), patient’s assessment of pain by VAS, Health Assessment Questionnaire Disability Index (HAQ-DI), morning stiffness duration and severity, 36-Item Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Impairment (WPAI), and EQ-5D 5-Level (EQ-5D-5L) index score. Least squares mean (LSM) changes from baseline to weeks 12 and 24 were based on an analysis of covariance model. Proportions of patients reporting improvements ≥ minimal clinically important differences (MCID) were compared using chi-square tests. Results: Data from 612 patients were analyzed (UPA, n=303; ABA, n=309). Mean age was 56 years and mean disease duration was 12 years. One-third received ≥2 prior bDMARDs and 72% received concomitant methotrexate at baseline. At week 12, UPA- vs ABA-treated patients had significantly greater improvements in PtGA, pain, HAQ-DI, morning stiffness severity, EQ-5D-5L, 2/4 WPAI domains, and 3/8 SF-36 domains and Physical Component Summary (PCS) scores (P<0.05); significant differences persisted at week 24 for HAQ-DI, morning stiffness severity, SF-36 PCS and bodily pain domain, and WPAI activity impairment domain. At week 12, significantly more UPA- vs ABA-treated patients reported improvements ≥MCID in HAQ-DI (74% vs 64%) and SF-36 PCS (79% vs 66%) and 4/8 domain scores (P<0.05). Conclusions: At week 12, UPA vs ABA treatment elicited greater improvements in key domains of physical functioning, pain, and general health and earlier improvements in HAQ-DI. Overall, more UPA- vs ABA-treated patients achieved ≥MCID in most PROs at all timepoints; however, not all differences were statistically significant. These data, however, highlight the faster response to UPA treatment. Trial registration: NCT03086343, March 22, 2017.

Patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplant (allo-HCT) require extensive care. Using the Merative MarketScan Commercial Claims and Encounters database (2016 Q1-2020 Q2), we quantified the costs of care and assessed real-world complication rates among commercially insured US patients diagnosed with a hematologic malignancy and aged between 12 and 64 years undergoing inpatient allo-HCT. Health care resource use and costs were assessed from 100 days before HCT to 100 days after HCT. Primary hospitalization was defined as the time from HCT until first discharge date. Incidence of complications was assessed using medical billing codes from HCT date to 100 days after HCT. Among the 1082 patients analyzed, allo-HCT grafts included peripheral blood (79%), bone marrow (11%), and umbilical cord blood (3%). In the 100 days after HCT, 52% of the patients experienced acute graft-versus-host disease; 21% had cytomegalovirus infection. The median primary hospitalization length of stay (LOS) was 28 days; 31% required readmission in first 100 days after HCT. Across the transplant period (14 days pretransplant to 100 days posttransplant), 44% of patients were admitted to the intensive care unit with a median LOS of 29 days. Among those with noncapitated health plans (n = 937), median cost of all-cause health care per patient during the transplant period was $331 827, which was driven by primary hospitalization and readmission. Additionally, the predicted median incremental costs per additional day in an inpatient setting increased with longer LOS (eg, $3381-$4071, 10th-20th day.) Thus, decreasing length of primary hospitalization and avoiding readmissions should significantly reduce the allo-HCT cost of care.

Multiple targeted immunomodulators (TIMs) for psoriatic arthritis (PsA) treatment are available, but limited studies have directly compared these agents. This study indirectly compared the efficacy of TNF-α, interleukins, and phosphodiesterase-4 inhibitors for treatment of active PsA. A systematic literature review was conducted to identify phase III randomized controlled trials (RCTs) for adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, ustekinumab, secukinumab, and apremilast in active PsA. Joint (ACR20/50/70) and skin outcomes (PASI75/90) at Week 24 with each TIM were estimated via a Bayesian network meta-analysis, and the incremental cost per responder over the first 24 weeks of treatment was calculated. Similar analyses were conducted in a subgroup of biologic-naïve patients. Seventeen RCTs were identified; 13 included ACR and/or PASI responses at Week 24. Among the overall population, patients receiving adalimumab, golimumab, and infliximab showed higher ACR20/50/70 (adalimumab: 61.2/42.8/40.8%, golimumab: 61.6/39.8/27.4%, infliximab: 56.2/57.1/34.2%) and PASI75/90 (72.7/55.5%, 74.1/57.2%, and 77.1/61.0%, respectively) responses at Week 24 compared with other TIMs. In terms of cost-effectiveness, these treatments were also associated with the lowest incremental cost per responder for both skin and joint outcomes. Similar rankings of efficacy and incremental cost per responder were observed in the analysis among biologic-naive patients. Adalimumab, golimumab, and infliximab were associated with higher efficacy and lower incremental costs per responder for both joint and skin responses in active PsA.

Omidubicel is an advanced cell therapy derived from umbilical cord blood (UCB) for use in allogeneic hematopoietic cell transplantation (HCT). A recent randomized phase 3 clinical trial demonstrated faster engraftment, shorter length of hospital stays, and lower rates of infection with omidubicel compared with standard UCB transplantation in patients with high-risk hematologic malignancies. Despite the proven clinical benefits of omidubicel, its impact on health-related quality of life (HRQL) from the patient's perspective has not been described. This study analyzed patient-reported HRQL measures collected prospectively in the randomized phase 3 trial comparing omidubicel to standard UCB transplantation. A total of 108 patients at 33 international stem cell transplantation centers underwent myeloablative allogeneic HCT with either omidubicel or standard UCB. Patients completed serial HRQL questionnaires at screening and on days 42, 100, 180, and 365 post-transplantation. The HRQL surveys included the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), a 50-item cancer-specific questionnaire assessing physical, functional, emotional, social/family, and HCT-specific well-being, and the EuroQol 5-Dimension 3-Level, a 5-item generic HRQL survey. A mixed model with repeated measures was used to compare changes in HRQL from baseline in the 2 treatment arms. The average change in HRQL scores over time was compared by estimating the difference in the area under the curve (AUC) in each treatment group. Seventy-five patients (omidubicel arm, n = 37; standard UCB arm, n = 38) who completed the FACT-BMT at baseline and on 1 or more follow-up visits were included in this study. Baseline characteristics were similar in the 2 treatment arms. Over the first year post-transplantation, the AUCs of mean changes in physical, functional, and total FACT-BMT scores indicated significantly better HRQL with omidubicel (P < .05), with mean differences across time points ranging from 1.4 to 3.1 points, 1.6 to 3.2 points, and 7.2 to 11.0 points, respectively. The minimal clinically important difference was exceeded at 1 or more time points for each of these measures. The HRQL improvements with omidubicel were observed as early as 42 days post-transplantation and persisted at 1 year, indicating the potential long-term benefits of omidubicel on HRQL. Across all patients, adverse clinical outcomes, such as grade 3 viral infections and lower rates of neutrophil engraftment, were associated with worse HRQL scores. The observed improvements in HRQL measures may reflect the known clinical benefits of omidubicel. Compared with standard UCB, allogeneic HCT with omidubicel resulted in significant and clinically meaningful improvements in patient-reported HRQL measures.

Background: Studies on real-world treatment patterns and long-term economic burden of Parkinson’s disease (PD) have been limited. Objective: To assess treatment patterns, healthcare resource utilization (HRU), and costs associated with PD symptoms and treatment-related adverse events (AEs) among Medicare beneficiaries in the United States. Methods: A 100% Medicare Fee-For-Service data (2006– 2020) of patients with PD were analyzed. PD treatment patterns were described for the subset of patients who had no previously observed PD treatments or diagnoses (ie, the incident cohort). HRU and healthcare costs associated with PD symptoms were assessed for all patients with PD (ie, the overall cohort) and that associated with treatment-related AEs were assessed for the subset of patients who received PD treatments after PD diagnosis (ie, the active treatment cohort), using longitudinal models with repeated measures. Results: Overall, 318,582 patients were included (mean age at PD diagnosis: 77.4 years; 53.3% female). Among patients in the incident cohort (N=214,829), 51.1% initiated levodopa monotherapy and 5.9% initiated dopamine agonists (DAs) monotherapy as first-line treatment. The proportion of incident patients treated with DAs and other PD therapies generally increased from post-diagnosis years 1 to 10. The median time from diagnosis to PD treatment initiation was 2.0 months; the median time to treatment discontinuation was the longest with levodopa (18.7 months), followed by DAs (9.5 months). In the overall cohort, PD symptoms, especially motor symptoms and severe motor symptoms, were associated with significantly higher rates of HRU and costs. In the active treatment cohort (N=234,298), treatment-related AEs were associated with significantly higher rates of HRU and medical costs. Conclusion: While levodopa is still the mainstay of PD management, considerable heterogeneity exists in real-world treatment patterns. Overall, PD symptoms and AEs were associated with significantly higher HRU and healthcare costs, suggesting unmet medical needs for PD treatments with better tolerability profiles.