Comparative effectiveness of cladribine tablets versus other oral disease-modifying treatments for multiple sclerosis: Results from MSBase registry.

BACKGROUND: Effectiveness of cladribine tablets, an oral disease-modifying treatment (DMT) for multiple sclerosis (MS), was established in clinical trials and confirmed with real-world experience. OBJECTIVES: Use real-world data to compare treatment patterns and clinical outcomes in people with MS (pwMS) treated with cladribine tablets versus other oral DMTs. METHODS: Retrospective treatment comparisons were based on data from the international MSBase registry. Eligible pwMS started treatment with cladribine, fingolimod, dimethyl fumarate, or teriflunomide tablets from 2018 to mid-2021 and were censored at treatment discontinuation/switch, death, loss to follow-up, pregnancy, or study period end. Treatment persistence was evaluated as time to discontinuation/switch; relapse outcomes included time to first relapse and annualized relapse rate (ARR). RESULTS: Cohorts included 633 pwMS receiving cladribine tablets, 1195 receiving fingolimod, 912 receiving dimethyl fumarate, and 735 receiving teriflunomide. Individuals treated with fingolimod, dimethyl fumarate, or teriflunomide switched treatment significantly more quickly than matched cladribine tablet cohorts (adjusted hazard ratio (95% confidence interval): 4.00 (2.54-6.32), 7.04 (4.16-11.93), and 6.52 (3.79-11.22), respectively). Cladribine tablet cohorts had significantly longer time-to-treatment discontinuation, time to first relapse, and lower ARR, compared with other oral DMT cohorts. CONCLUSION: Cladribine tablets were associated with a significantly greater real-world treatment persistence and more favorable relapse outcomes than all oral DMT comparators.

Upadacitinib improves patient-reported outcomes vs placebo or adalimumab in patients with rheumatoid arthritis: results from SELECT-COMPARE.

OBJECTIVE: To evaluate the impact of upadacitinib vs placebo and adalimumab treatment, on patient-reported outcomes (PROs) in SELECT-COMPARE in an active RA population with inadequate responses to MTX (MTX-IR). METHODS: PROs in patients receiving upadacitinib (15 mg QD), placebo, or adalimumab (40 mg EOW) while on background MTX were evaluated over 48 weeks. PROs included Patient Global Assessment of Disease Activity (PtGA) and pain by visual analogue scale (VAS), the HAQ Disability Index (HAQ-DI), the 36-Item Short Form Survey (SF-36), morning (AM) stiffness duration and severity, the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and work instability. Least squares mean (LSM) changes and proportions of patients reporting improvements ≥ minimal clinically important differences (MCIDs) and scores ≥ normative values were evaluated. RESULTS: Upadacitinib and adalimumab resulted in greater LSM changes from baseline vs placebo across all PROs (P < 0.05) at week 12, and pain and AM stiffness severity (P < 0.05) at week 2. More upadacitinib- vs placebo-treated (P < 0.05) and similar percentages of upadacitinib- vs adalimumab-treated patients reported improvements ≥ MCID across all PROs at week 12. Upadacitinib vs adalimumab resulted in greater LSM changes from baseline in PtGA, pain, HAQ-DI, stiffness severity, FACIT-F, and the SF-36 Physical Component Summary (PCS) (all P < 0.05) at week 12. More upadacitinib- vs adalimumab-treated patients reported scores ≥ normative values in HAQ-DI and SF-36 PCS (P < 0.05) at week 12. More upadacitinib- vs adalimumab-treated patients maintained clinically meaningful improvements in PtGA, pain, HAQ-DI, FACIT-F, and AM stiffness through 48 weeks. CONCLUSION: In MTX-IR patients with RA, treatment with upadacitinib resulted in statistically significant and clinically meaningful improvements in PROs equivalent to or greater than with adalimumab. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02629159.

Upadacitinib monotherapy improves patient-reported outcomes in rheumatoid arthritis: results from SELECT-EARLY and SELECT-MONOTHERAPY.

OBJECTIVE: To evaluate the effect of upadacitinib (UPA) monotherapy vs MTX on patient-reported outcomes (PROs) in patients with RA who were MTX-naïve or who had an inadequate response to MTX (MTX-IR). METHODS: PROs from the SELECT-EARLY and SELECT-MONOTHERAPY randomized controlled trials were evaluated at Weeks 2 and 12/14. Patients were ≥18 years of age with RA symptoms for ≥6 weeks (SELECT-EARLY, MTX-naïve) or diagnosed RA for ≥3 months (SELECT-MONOTHERAPY, MTX-IR) and received UPA monotherapy (15 or 30 mg) or MTX. PROs included Patient Global Assessment of Disease Activity (PtGA), pain visual analogue scale, HAQ Disability Index (HAQ-DI), morning stiffness duration/severity, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (SELECT-EARLY), health-related quality of life (HRQOL) by the 36-iem Short Form Health Survey and Work Productivity and Activity Impairment (WPAI; SELECT-EARLY). Least square mean (LSM) changes and proportions of patients reporting improvements greater than or equal to the minimum clinically important differences and normative values were determined. RESULTS: In 945 MTX-naïve and 648 MTX-IR patients, UPA monotherapy (15 mg, 30 mg) vs MTX resulted in greater reported LSM changes from baseline at Weeks 12/14 in PtGA, pain, HAQ-DI, morning stiffness duration/severity, FACIT-F (SELECT-EARLY), HRQOL and WPAI (SELECT-EARLY). These changes were statistically significant with both doses of UPA vs MTX at Weeks 12/14 in both RCTs. Improvements were reported as early as week 2. Compared with MTX, more UPA-treated MTX-naïve and MTX-IR patients reported improvements greater than or equal to the minimum clinically important differences and scores greater than or equal to normative values. CONCLUSION: Among MTX-naïve and MTX-IR patients with active RA, UPA monotherapy at 15 or 30 mg for 12/14 weeks resulted in statistically significant and clinically meaningful improvements in pain, physical function, morning stiffness, HRQOL and WPAI compared with MTX alone. CLINICAL TRIAL REGISTRATION NUMBER: SELECT-EARLY (NCT02706873) and SELECT-MONOTHERAPY (NCT02706951) are registered with ClinicalTrials.gov.

Risk of Ocular Complications in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis.

PURPOSE: Noninfectious uveitis results in vision loss and ocular complications without adequate treatment. We compared the risk of developing ocular complications between patients with noninfectious intermediate uveitis, posterior uveitis, or panuveitis (NIIPPU) and matched controls. DESIGN: Retrospective analysis of insurance claims data (OptumHealth, Eden Prairie, MN; January 1, 1998-March 31, 2012). PARTICIPANTS: Cases 18 to 64 years of age with 2 or more NIIPPU diagnoses (International Classification of Diseases, 9th Revision, Clinical Modification codes) were matched 1:1 by sex, age, region, company, employment status, and index date with controls without uveitis. Patients with an ocular complication during baseline were excluded. METHODS: Continuous eligibility for 6 months or more before the first NIIPPU diagnosis date was required. Risks of ocular complications developing during patients' continuous eligibility in the study period were compared using unadjusted Kaplan-Meier survival analysis to estimate risk of and time to complications and adjusted Cox regression analysis to estimate hazard ratios (HRs). MAIN OUTCOME MEASURES: Percentages of cases and controls who demonstrate ocular complications and 1-, 5-, and 10-year risks and HRs for each complication. RESULTS: Mean age of the 1769 cases and matched controls was 47 years and 47% were men; 302 cases had persistent NIIPPU. During the study period, NIIPPU cases had a higher risk of any ocular complication (P < 0.001); the 5-year risk of any ocular complication was 66% for patients versus 24% for controls. Specifically, NIIPPU patients had greater 5-year risks of glaucoma (20% vs. 9%), cataract (35% vs. 13%), visual disturbance (29% vs. 9%), blindness or low vision (5% vs. 0.5%), retinal detachment (11% vs. 0.8%), and retinal disorder (28% vs. 2%) compared with controls. Hazard ratios indicated greater risks of ocular complications in cases versus controls during the overall observation period (HR, 5.2 for any ocular complication; HR, 4.8 for visual disturbance; HR, 3.2 for cataract; and HR, 2.7 for glaucoma; all P < 0.001). Hazard ratios for persistent cases indicated even greater risks. CONCLUSIONS: Noninfectious intermediate uveitis, posterior uveitis, or panuveitis, particularly persistent disease, is associated with a substantial risk of ocular complications. Optimal treatment initiatives remain imperative to reduce the ocular complication-related burden of NIIPPU.

Direct Costs in Patients with Celiac Disease in the USA: A Retrospective Claims Analysis.

BACKGROUND: Celiac disease (CeD) is an autoimmune disease triggered by gluten ingestion. AIM: We assessed total direct costs burden associated with CeD in patients with CeD versus patients without CeD using administrative claims data. METHODS: Patients with CeD (cases) with ≥1 occurrences of CeD diagnosis were selected at a randomly chosen date (index date) from the OptumHealth Reporting and Insights database from 01/01/1998 through 03/31/2013. Cases were continuously enrolled throughout baseline (1 year before index date) and study (1 year after index date) periods. Cases were categorized as full remission and partial remission and matched 1:1 based on age, sex, region, index date, company, and employment status. Total all-cause and CeD-related costs were calculated. RESULTS: A total of 12,187 cases were matched with an equal number of controls. Mean total all-cause costs were $12,217 in cases versus $4935 in controls (P < 0.0001). In full remission (N = 10,181 [83.5 %]) and partial remission (N = 2006 [16.5 %]) cases, mean total all-cause direct costs (cases versus controls) were $11,038 versus $4962 and $18,206 versus $4796, respectively. All-cause medical costs ($9839 for all cases, $8723 for full remission cases, $15,499 for partial remission cases) accounted for the majority of all-cause total costs and included outpatient costs ($6675; $6456; and $7785, respectively) and hospitalizations ($2776; $1963; and $6906, respectively). CeD-related medical costs were 13 and 27 % of all-cause medical costs for all cases and partial remission cases, respectively. CONCLUSIONS: Patients with CeD and partial remission of CeD incurred significantly higher (2.5 and 3.8 times) total all-cause costs compared with matched controls.

U.S. emergency departments visits resulting from poor medication adherence: 2005-07.

OBJECTIVES: To describe characteristics and trends for emergency department visits related to medication nonadherence and to identify associations between patient characteristics and emergency department visits related to medication nonadherence. DESIGN: Retrospective cross-sectional study. SETTING: National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2005 to 2007. PATIENTS: Patients who had an emergency department visit for medication nonadherence. INTERVENTION: NHAMCS data were weighted to yield national estimates of emergency department visits related to medication nonadherence. Descriptive frequencies were calculated for visits related and unrelated to medication adherence. A binary logistic regression model was used to identify covariates for nonadherence. MAIN OUTCOME MEASURES: National estimates of emergency department visits related to medication nonadherence. RESULTS: An estimated 456,209 ± 68,940 (mean ± SD) nonadherence-related visits occurred. Of visits related to nonadherence, 29% resulted from mental health disorders. Significant covariates of nonadherence-related visits included age, payment source, and primary diagnosis. Visits for patients with mental illness (odds ratio 22.74 [95% CI 14.68-34.20]), type 2 diabetes (15.80 [5.20-48.06]), nondependent abuse of drugs (11.85 [3.83-36.65]), or essential hypertension (11.06 [3.99-30.61]) were significantly associated with the probability that an emergency department visit was related to nonadherence. More than 20% of emergency department visits related to medication nonadherence resulted in hospital admission, whereas only 12.7% of visits unrelated to nonadherence resulted in hospital admission ( P < 0.0001). CONCLUSION: Medication nonadherence is an important problem. Targeting patients at high risk for nonadherence, especially patients with mental illness, may improve medication adherence and prevent future emergency department visits.

Real-world treatment patterns and effectiveness of cladribine tablets in patients with relapsing forms of multiple sclerosis in the United States.

BACKGROUND: Real-world evidence on the use of cladribine tablets (CladT) for relapsing forms of multiple sclerosis (RMS) in the United States is emerging. The objective of this study was to assess the real-world treatment patterns and effectiveness of CladT in RMS. METHODS: Adults with RMS initiating CladT were selected from the Symphony Integrated Dataverse. Baseline and follow-up periods were the 12 months before and 24 months after CladT initiation (index date). Switching to another disease-modifying therapy (DMT) and number of CladT courses were described during follow-up. Annualized relapse rate (ARR), MS disease severity, Expanded Disability Status Scale-Derived Disability Indicators (EDSS-DDI), corticosteroid use, and healthcare resource utilization (HRU) were described during Years 1 and 2 of follow-up and compared with baseline. RESULTS: A total of 539 CladT-treated patients were included (mean age: 49.9 years; 77.6 % female). Over the 2-year follow-up, 91 % and 59 % of patients had one and two CladT courses, respectively, and 7 % of patients had evidence of switching to another DMT. ARR, MS disease severity score, and corticosteroid use decreased significantly during follow-up compared with baseline, while EDSS-DDI remained stable. All-cause and MS-related HRU decreased during follow-up. CONCLUSION: CladT-treated patients with RMS had low switch rates, reduced ARR, disease severity, corticosteroid use, and HRU.

A Real-World Effectiveness Study Using a Mobile Application to Evaluate Early Outcomes with Upadacitinib in Rheumatoid Arthritis.

INTRODUCTION: The impact of upadacitinib on rheumatoid arthritis (RA) symptoms was evaluated during the first 12 weeks of treatment via patient-reported outcomes (PROs) using a mobile health application (app). METHODS: Participating rheumatologists from the CorEvitas RA Registry (prospective, observational cohort) recruited patients with RA initiating upadacitinib treatment. A modified version of the ArthritisPower® app was used to collect PROs, including the Routine Assessment of Patient Index Data 3 (RAPID3), duration of morning joint stiffness, and the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue 7a Short Form at baseline and weeks 1-4, 8, and 12. RAPID3 responses over time were assessed using Kaplan-Meier estimation to determine the proportion of patients achieving disease activity improvement and minimal clinically important difference (MCID). Results were analyzed for all patients initiating upadacitinib and a subsample of TNF inhibitor (TNFi)-experienced patients with moderate to severe disease at baseline. RESULTS: A total of 103 patients with RA initiating upadacitinib (62.1% TNFi-experienced) were included. At week 12, 53 patients (51.4%) completed the study and provided PRO data via the app. Among all patients, improvements in RAPID3, pain, morning stiffness, and fatigue were observed at week 1 and were maintained or further improved through week 12. At week 12, 37.5% of patients achieved RAPID3 low disease activity. Starting at week 1, improvements in RAPID3 disease activity category (19.4% of patients) and achievement of MCID (16.3%) were reported, with nearly 50% of patients achieving these outcomes by week 4 (RAPID3 category: 48.8%; MCID: 49.2%) and 60% by week 12 (RAPID3 category: 59.6%; MCID: 59.8%). TNFi-experienced patients generally reported similar outcomes. Patient-reported medication convenience and compliance were generally high. CONCLUSIONS: In this real-world cohort of patients with RA, treatment with upadacitinib was associated with early and significant improvement in RAPID3, pain, morning stiffness, and fatigue regardless of prior TNFi experience. Clinically meaningful improvement in RAPID3 patient-reported disease activity was observed as early as week 1, with continued improvement reported through week 12.

A plain language summary on the effectiveness of cladribine tablets compared with other oral treatments for multiple sclerosis: results from the MSBase registry.

WHAT IS THIS SUMMARY ABOUT?: Patient registries contain anonymous data from people who share the same medical condition. The MSBase registry contains information from over 80,000 people living with multiple sclerosis (MS) across 41 countries. Using information from the MSBase registry, the GLIMPSE (Generating Learnings In MultiPle SclErosis) study looked at real-life outcomes in 3475 people living with MS who were treated with cladribine tablets (Mavenclad®) compared with other oral treatments. WHAT WERE THE RESULTS?: Results showed that people treated with cladribine tablets stayed on treatment for longer than other treatments given by mouth. They also had fewer relapses (also called flare ups of symptoms) than people who received a different oral treatment for their MS. WHAT DO THE RESULTS MEAN?: The results provide evidence that, compared with other oral treatments for MS, cladribine tablets are an effective medicine for people living with MS.

National burden of pediatric hospitalizations for inflammatory bowel disease: results from the 2006 Kids' Inpatient Database.

OBJECTIVES: : The objective of the present study was to quantify the national pediatric inpatient inflammatory bowel disease (IBD) burden in terms of the number of IBD-related hospitalizations, the number of days spent in the hospital, and hospitalization costs. METHODS: : Hospitalizations for children and adolescents 20 years and younger with a primary diagnosis of either Crohn disease (CD) or ulcerative colitis (UC) were selected from the 2006 Kids' Inpatient Database (KID). Length of the hospital stay in days (LOS) and charges for the hospitalization were found directly in the Kids' Inpatient Database, and cost was calculated using the hospital's cost-to-charge ratio. Predictor variables included patient characteristics, such as age and severity of illness, and hospital characteristics. Ordinary-least-squares regressions were developed and estimated to explain hospitalization costs. RESULTS: : In 2006, there were 10,777 IBD-related hospitalizations. The total and mean costs for CD were $66.3 million and $10,176 (95% confidence interval [CI] $9647-$10,705), and for UC were $48.6 million and $11,836 (95% CI $10,760-$12,912). For CD, 0- to 5-year-old patients had the highest mean LOS (8.10, 95% CI 5.53-10.67, days) and mean cost ($13,894, 95% CI $9053-$18,735), whereas, for UC, 11- to 15-year-old patients had the highest mean LOS (7.49, 95% CI 6.88-8.10, 95% CI 5.53-10.67, days) and mean cost ($13,407, 95% CI $11,704-$15,110). CONCLUSIONS: : For a pediatric disease with a rather low prevalence rate, the estimated annual inpatient pediatric burden of IBD is a sizeable $152.4 million (2010 US$) and 64,985 days spent in the hospital. As medications and outpatient treatments improve for the treatment of IBD, there is an opportunity for significant reduction in inpatient burden.

Patient-reported outcomes of upadacitinib versus abatacept in patients with rheumatoid arthritis and an inadequate response to biologic disease-modifying antirheumatic drugs: 12- and 24-week results of a phase 3 trial.

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.

The national burden of E-code-identified adverse drug events among hospitalized children using a national discharge database.

PURPOSE: The purpose of this study was to provide a national-level assessment of pediatric adverse drug events (ADEs), including types, frequencies, and burdens. METHODS: Discharge data were obtained from the 2006 Kids' Inpatient Database. ADEs were identified by the International Classification of Diseases, Ninth Revision, Clinical Modification and supplemental E codes as adverse effects (AEs), accidental poisonings (APs), or those involving neuropathy, dermatitis, and contact dermatitis. For ADEs occurring in the hospital, visits were matched, by all patient refined diagnostic-related group, age, and gender, to one control visit without an ADE code. Burden was measured as excess length of stay and excess cost relative to the control. Using regression analysis, we obtained estimates on the effects of over 100 predictors on excess length of stay and excess cost of cases relative to the control. RESULTS: Out of 7,558,812 hospital discharges in 2006, there were 84,510 ADEs identified during 69,620 visits (0.9% of the total number of discharges); 55,285 (79.4%) visits involved an AE; and 13,630 (19.6%) involved an AP; 12,151 (17.5%) were characterized by an ADE (usually an AP) at admission. The national pediatric ADE burden was estimated at 104,230 days with direct costs of $252.9 million. The most common AEs occurred with antineoplastic and immunosuppressive drugs (20.4%) and adrenal corticosteroids (12.5%). The most common APs involved aromatic analgesics (13.7%), cardiovascular drugs (9.5%), antidepressants (8.6%), and benzodiazepine tranquilizers (8.0%). CONCLUSION: By identifying specific ADEs that occur most often and/or have the highest burden, physicians and hospital administrators can better target their strategies for reducing pediatric medication-related harm.

Economic Benefit from Improvements in Quality of Life with Upadacitinib: Comparisons with Tofacitinib and Methotrexate in Patients with Rheumatoid Arthritis.

INTRODUCTION: To compare the economic benefit of upadacitinib combination therapy versus tofacitinib combination therapy and upadacitinib monotherapy versus methotrexate monotherapy from improvements in health-related quality of life (HRQOL) in patients with rheumatoid arthritis (RA). METHODS: Data were analyzed from two trials of upadacitinib (SELECT-NEXT and SELECT-MONOTHERAPY) and one trial of tofacitinib (ORAL-Standard) that collected HRQOL measurements using the Short Form 36 (SF-36) Health Survey in patients with RA. Direct medical costs per patient per month (PPPM) for patients receiving upadacitinib 15 mg once daily and methotrexate were derived from observed SF-36 Physical (PCS) and Mental Component Summary (MCS) scores in the SELECT trials using a regression algorithm. Direct medical costs PPPM for patients receiving tofacitinib 5 mg twice daily were obtained from a published analysis of SF-36 PCS and MCS scores observed in the ORAL-Standard trial. Short-term (12-14 weeks) and long-term (48 weeks) estimates of direct medical costs PPPM were compared between upadacitinib and tofacitinib and between upadacitinib and methotrexate. RESULTS: Over 12 weeks, direct medical costs PPPM were $252 lower (95% CI $72, $446) for upadacitinib-treated patients versus tofacitinib-treated patients. Medical costs PPPM at weeks 24 and 48 and cumulative costs over the entire 48-week period (difference $1759; 95% CI $1162, $2449) were significantly lower for upadacitinib than for tofacitinib. Over 14 weeks, direct medical costs PPPM were $399 lower (95% CI $158, $620) for patients treated with upadacitinib monotherapy compared with those treated with methotrexate alone. Direct medical costs at week 48 and cumulative costs over the entire 48-week period (difference $2044; 95% CI $1221, $2846) were significantly lower for upadacitinib monotherapy compared with methotrexate alone. CONCLUSION: In the short and long term, upadacitinib combination therapy versus tofacitinib combination therapy and upadacitinib monotherapy versus methotrexate monotherapy were associated with significantly lower direct medical costs for patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02675426, NCT02706951, and NCT00853385.

Healthcare Costs of Not Achieving Remission in Patients with Rheumatoid Arthritis in the United States: A Retrospective Cohort Study.

INTRODUCTION: To compare all-cause and rheumatoid arthritis (RA)-related healthcare costs and resource use in patients with RA who do not achieve remission versus those who achieve remission, using clinical practice data. METHODS: Data were derived from Optum electronic health records linked to claims from commercial and Medicare Advantage health plans. Two cohorts were created: remission and non-remission. Remission was defined as Disease Activity Score 28-joint count with the C-reactive protein level or erythrocyte sedimentation rate (DAS28-CRP/ESR) < 2.6 or Routine Assessment of Patient Index Data 3 (RAPID3 ≤ 3.0). Outcomes were all-cause and RA-related costs and resource use during a 1-year follow-up period. A weighted generalized linear regression and negative binomial regression were used to estimate adjusted annual costs and resource use, respectively, controlling for confounding factors, including patient and socio-demographic characteristics. RESULTS: Data from 335 patients (remission: 125; non-remission: 210) were analyzed. Annual all-cause total costs were significantly less in the remission versus non-remission cohort ($30,427 vs. $38,645, respectively; cost ratio [CR] = 0.79; 95% CI 0.63, 0.99). All-cause resource use (mean number of visits) was less in the remission versus non-remission cohort: inpatient (0.23 vs. 0.63; visit ratio [VR] = 0.36; 95% CI 0.19, 0.70), emergency department (0.36 vs. 0.77; VR = 0.47; 95% CI 0.30, 0.74), and outpatient visits (20.7 vs. 28.5; VR = 0.73; 95% CI 0.62, 0.86). Annual RA-related total costs were similar in both cohorts; however, RA-related medical costs were numerically lower in the remission versus non-remission cohort ($8,594 vs. $10,002, respectively; CR = 0.86; 95% CI 0.59, 1.25). RA-related resource use was less in the remission versus non-remission cohort. CONCLUSIONS: Significant economic burden was associated with patients who did not achieve remission compared with those who did achieve remission.

Cost-utility analyses of targeted immunomodulators in rheumatoid arthritis: systematic review.

Aims: Cost-utility (CU) modeling is a common technique used to determine whether new treatments represent good value for money. As with any modeling exercise, findings are a direct result of methodology choices, which may vary widely. Several targeted immuno-modulators have been launched in recent years to treat moderate-to-severe rheumatoid arthritis (RA) which have been evaluated using CU methods. Our objectives were to identify common and innovative modeling choices in moderate-to-severe RA and to highlight their implications for future models in RA.Materials and methods: A systematic literature search was conducted to identify CU models in moderate-to-severe RA published from January 2013 to June 2019. Studies must have included an active comparator and used quality-adjusted life-years (QALYs) as the common measure of effectiveness. Modeling methods were characterized by stakeholder perspective, simulation type, mapping between parameters, and data sources.Results: Thirty-one published modeling studies were reviewed spanning 13 countries and 9 drugs, with common methodological choices and innovations observed among them. Over the evaluated time period, we observed common methods and assumptions that are becoming more prominent in the RA CU modeling landscape, including patient-level simulations, two-stage models combining trial results and real-world evidence, real-world treatment durations, long-term health consequences, and Health Assessment Questionnaire (HAQ)-related hospitalization costs. Models that consider the societal perspective are increasingly being developed as well.Limitations: This review did not consider studies that did not report QALYs as a utility measure, models published only as conference abstracts, or cost-consequence models that did not report an incremental CU ratio.Conclusions: CU modeling for RA increasingly reflects real-world conditions and patient experiences which are anticipated to provide better information in the assessment of health technologies. Future CU models in RA should consider applying the observed advances in modeling choices to optimize their CU predictions and simulation of real-world outcomes.

Economic burden of fatigue or morning stiffness among patients with rheumatoid arthritis: a retrospective analysis from real-world data.

Objective: Determine healthcare resource utilization (HCRU) and costs associated with fatigue and stiffness among patients with rheumatoid arthritis (RA).Methods: A retrospective claims analysis compared RA patients with fatigue or stiffness to matched RA control patients with neither. Claims from a large US commercial insurance database identified new cases of stiffness/fatigue among newly diagnosed patients. Study patients had ≥2 medical claims for RA ≥45 days apart, continuous insurance coverage ≥12 months before RA index (baseline period) and ≥12 months after fatigue/stiffness index (follow-up period). Controls had no diagnosis of fatigue or stiffness ≥12 months before index. Cases had ≥1 claim of fatigue/stiffness after RA index; the first such claim was the index date. Multivariate logistic regressions, adjusting for baseline demographics, comorbidities, medication use and HCRU, were used to predict the propensity of having a fatigue/stiffness diagnosis. Controls were propensity-score matched to cases. Generalized linear models estimated all-cause and RA-specific costs associated with resource use as well as prescription drugs, adjusting for any unbalanced covariates after propensity-score matching.Results: Approximately 32% of newly diagnosed RA patients suffer from fatigue/stiffness. Matched cohorts were analyzed: fatigue vs. control; stiffness vs. control; fatigue and stiffness vs. control. After RA diagnosis, hospitalizations increased: 83% for fatigue, 117% for stiffness and 148% for both; total office visits increased 63%, 113% and 135%, respectively. Greater HCRU yielded significantly greater (all p < .001) per-patient-per-year hospitalization costs vs. matched controls: fatigue ($2554 vs. $1293); stiffness ($2792 vs. $892); fatigue and stiffness ($3322 vs. $1033). Per-patient-per-year costs of office visits increased significantly (all p < .001) vs. matched controls: fatigue ($1373 vs. $908); stiffness ($1580 vs. $761); fatigue and stiffness ($1989 vs. $921).Conclusions: RA patients with fatigue and/or stiffness report more HCRU and incur significantly higher medical costs than RA patients without them.

Comparative Efficacy of JAK Inhibitors for Moderate-To-Severe Rheumatoid Arthritis: A Network Meta-Analysis.

INTRODUCTION: Janus kinase (JAK) inhibitors are a class of targeted therapies for rheumatoid arthritis (RA) with established clinical efficacy. However, little is known about their efficacy compared with each other. This network meta-analysis (NMA) estimated the comparative efficacy of JAK inhibitors currently approved for RA. METHODS: A targeted literature review was conducted for phase III randomized controlled trials (RCTs) evaluating the efficacy of three approved JAK inhibitors (tofacitinib, baricitinib, and upadacitinib) as monotherapy or combination therapy among patients with moderate-to-severe RA who had inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARD-IR). Using Bayesian NMA, American College of Rheumatology (ACR) 20/50/70 responses and clinical remission (defined as DAS28-CRP < 2.6) were evaluated separately at 12 and 24 weeks. RESULTS: Eleven RCTs were identified and included in the NMA. All JAK inhibitors demonstrated significantly better efficacy than csDMARD. Among combination therapies, upadacitinib 15 mg had the highest 12-week ACR50 responses (median [95% credible interval]: 43.4% [33.4%, 54.5%]), followed by tofacitinib 5 mg (38.7% [28.6%, 49.8%]), baricitinib 2 mg (37.1% [25.0%, 50.6%]), and baricitinib 4 mg (36.7%, [27.2%, 47.0%]). Similar results were observed for ACR20/70 and at week 24. Upadacitinib 15 mg + csDMARD was also found to have the highest clinical remission rates at week 12 (29.8% [16.9%, 47.0%]), followed by tofacitinib 5 mg (24.3%, [12.7%, 40.2%]), baricitinib 4 mg (22.8%, [11.8%, 37.5%]), and baricitinib 2 mg (20.1%, [8.6%, 37.4%]). Similar results were seen at week 24. Among monotherapies, upadacitinib had a higher ACR50 response (38.5% [25.3%, 53.2%]) than tofacitinib (30.4% [18.3%, 45.5%]). The differences in efficacy measures were not statistically significant between the JAK inhibitors. CONCLUSIONS: The NMA found that upadacitinib 15 mg once daily had numerically higher efficacy in terms of ACR response and clinical remission among approved JAK combination therapies and monotherapies for csDMARD-IR patients with RA.

Correction to: Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: results from SELECT-NEXT.

An amendment to this paper has been published and can be accessed via the original article.

Development and content validity of new patient-reported outcome questionnaires to assess the signs and symptoms and impact of atopic dermatitis: the Atopic Dermatitis Symptom Scale (ADerm-SS) and the Atopic Dermatitis Impact Scale (ADerm-IS).

Objectives: Atopic dermatitis (AD) is a chronic, relapsing skin condition, with signs and symptoms that impact patients' lives and are best measured from the patient perspective. Therefore, there is a need for AD-specific questionnaires that are consistent with Food and Drug Administration guidance and best measurement practices, assessing sign and symptom severity and associated impacts, to support treatment efficacy in regulated trials. The objectives were to develop patient-reported outcome (PRO) questionnaires assessing sign and symptom severity, as well as impacts of moderate-to-severe adult AD. Methods: A targeted literature review and meetings with clinical experts (dermatologists) were conducted to identify AD-related sign, symptom, and impact concepts. Results were harmonized and used to construct two draft PRO questionnaires: the Atopic Dermatitis Symptom Scale (ADerm-SS; 11 items) and the Atopic Dermatitis Impact Scale (ADerm-IS; 10 items). The content validity and questionnaire content were evaluated via qualitative concept elicitation/cognitive debriefing interviews with adult patients with moderate-to-severe AD. Results: From the literature (n = 13 articles), 13 sign and symptom and 43 impact concepts were identified, while 21 sign and symptom and 48 impacts were elicited from experts (n = 3). During the patient interviews (n = 15), 19 sign and symptom and 41 impact concepts were reported, the majority of which were evaluated by the ADerm-SS and ADerm-IS, thus substantiating the content of both questionnaires. Additionally, patients interpreted both questionnaires as intended by the developers. Conclusions: The ADerm-SS and ADerm-IS can be regarded as content-valid PRO questionnaires for moderate-to-severe AD.

Effects of upadacitinib on patient-reported outcomes: results from SELECT-BEYOND, a phase 3 randomized trial in patients with rheumatoid arthritis and inadequate responses to biologic disease-modifying antirheumatic drugs.

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.