Tofacitinib Efficacy in Patients with Rheumatoid Arthritis and Probable Depression/Anxiety: Post Hoc Analysis of Phase 3 and 3b/4 Randomized Controlled Trials.

INTRODUCTION: The aim of our work is to assess the prevalence of probable major depressive disorder and/or probable generalized anxiety disorder (pMDD/pGAD) in patients with moderate to severe rheumatoid arthritis (RA), and to evaluate the efficacy of tofacitinib on RA symptoms stratified by baseline pMDD/pGAD status. METHODS: Data were pooled from five phase 3 randomized controlled trials (RCTs) and one phase 3b/4 RCT, assessing tofacitinib 5 or 10 mg twice daily (BID), adalimumab (two RCTs), or placebo. pMDD/pGAD was defined as Short Form-36 Health Survey (SF-36) Mental Component Summary (MCS) score ≤ 38. Efficacy outcomes over 12 months included least squares mean change from baseline in SF-36 MCS score and Health Assessment Questionnaire-Disability Index, proportions of patients with pMDD/pGAD in those with baseline pMDD/pGAD, and American College of Rheumatology 20/50/70 response, and Disease Activity Score in 28 joints, erythrocyte sedimentation rate remission (< 2.6) rates. RESULTS: A total of 4404 patients with non-missing baseline values were included. Baseline pMDD/pGAD was reported by 44.5%, 39.8%, 45.4%, and 39.1% of patients receiving tofacitinib 5 mg BID, tofacitinib 10 mg BID, adalimumab, and placebo, respectively. SF-36 MCS improvements were greater for tofacitinib versus adalimumab/placebo through month 6, with numerical improvements for tofacitinib versus adalimumab sustained through month 12, when the proportions of patients with baseline pMDD/pGAD who continued to have pMDD/pGAD were reduced. RA efficacy outcomes were generally similar in patients with/without baseline pMDD/pGAD. CONCLUSIONS: The percentage of patients with pMDD/pGAD reduced from baseline over 1 year of treatment with tofacitinib or adalimumab. Effective treatment of underlying RA may lead to improvements in depression and anxiety, based on the SF-36 MCS. Specially designed studies using gold-standard diagnostic tools would be warranted to investigate this further. Video Abstract available for this article. TRIAL REGISTRATION: NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT02187055. Video Abstract (MP4 204475 KB).

Tofacitinib is a medicine used to treat rheumatoid arthritis (swollen and painful joints). A total of 4400 patients with moderate or severe rheumatoid arthritis who were taking part in tofacitinib clinical trials completed a survey about their general health and well-being at that time. We used their answers to determine whether they were likely to have depression or anxiety. We then looked at how common depression or anxiety was in patients with rheumatoid arthritis, and whether having depression or anxiety affected how patients responded to tofacitinib treatment. It is important to note that tofacitinib is not approved for the treatment of depression or anxiety, and these clinical trials were not designed to assess whether tofacitinib improved depression or anxiety symptoms. About 40% of patients likely had depression or anxiety when they started a clinical trial. This percentage decreased among patients who received tofacitinib treatment over a year. Patients treated with tofacitinib showed more improvement in their depression or anxiety than those treated with placebo. Over a year of treatment, tofacitinib improved signs and symptoms of rheumatoid arthritis, for example, the number of swollen or painful joints and fatigue. Having depression or anxiety did not change the way that patients responded to tofacitinib. This research shows how treating rheumatoid arthritis symptoms may also improve depression and anxiety symptoms. However, specially designed studies are needed to confirm this.

Experience with Tofacitinib in Patients with Ulcerative Colitis: Data from a United States Claims Database.

BACKGROUND: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). AIMS: To evaluate real-world data in US patients with UC receiving tofacitinib. METHODS: Characteristics and outcomes of patients with UC initiating tofacitinib between 2018 and 2019 were assessed using data from the IBM® MarketScan® claims database. The index date was the first tofacitinib claim; pre- and post-index periods were 12 months. Outcomes included tofacitinib adherence/persistence, oral corticosteroid (OCS) use, and healthcare resource utilization (HCRU) and costs. RESULTS: Of 276 patients with UC who initiated tofacitinib, 68 (24.6%) were bio-naïve, and 208 (75.4%) bio-experienced. At month 12, overall median tofacitinib adherence (proportion of days covered) was 0.82 (mean 0.68); 43.8% of patients discontinued tofacitinib (90-day gap). Of patients receiving OCS during the post-index 16-week tapering period, 40.4% discontinued OCS up to 12 months post-index. OCS use decreased in patients continuing tofacitinib versus those discontinuing tofacitinib (29.7% vs 59.5%, respectively). Reductions in all-cause and UC-related outpatient visits were observed for bio-naïve (- 1.34 and - 0.88, respectively) and bio-experienced (- 4.72 and - 5.16, respectively) patients, post-index. Decreased UC-related costs per year were observed for bio-experienced patients (difference in post-index vs pre-index, - US$12,448; driven by changes in pharmacy costs), but not for bio-naïve patients (US$47,152). CONCLUSIONS: In this real-world analysis in a mostly bio-experienced population, the majority of US patients with UC initiating tofacitinib remained on therapy at 12 months, and OCS use was reduced with tofacitinib treatment. HCRU (all patients) and UC-related costs were reduced in bio-experienced patients. The majority of patients with ulcerative colitis starting tofacitinib in this real-world study continued therapy at 12 months; there was a reduction in the use of steroids, and a decrease in healthcare resournce utilization and costs.

Sex differences in the efficacy, safety and persistence of patients with psoriatic arthritis treated with tofacitinib: a post-hoc analysis of phase 3 trials and long-term extension.

BACKGROUND: Evaluate the impact of sex on tofacitinib efficacy, safety and persistence (time to discontinuation) in patients with psoriatic arthritis (PsA). METHODS: Data were pooled from two phase 3 randomised controlled trials. Patients were randomised to tofacitinib 5 mg or 10 mg two times per day, adalimumab 40 mg every 2 weeks or placebo. Efficacy outcomes to month 12 included American College of Rheumatology (ACR)20/50/70, minimal disease activity (MDA), Psoriasis Area Severity Index (PASI)75, change from baseline (∆) in Health Assessment Questionnaire-Disability Index (HAQ-DI) and ∆Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Safety was assessed to month 12 and persistence was assessed to month 42 of a long-term extension study. RESULTS: Overall, 816 patients were included (54.3% females). At baseline, higher tender joint counts, enthesitis scores and worse HAQ-DI and FACIT-F were reported in females versus males; presence of dactylitis and PASI were greater in males versus females. At month 3, tofacitinib efficacy generally exceeded placebo in both sexes. Overall, similar ACR20/50/70, PASI75, ∆HAQ-DI and ∆FACIT-F were observed for tofacitinib between sexes; females were less likely to achieve MDA. Similar proportions of males/females receiving tofacitinib (both doses) experienced treatment-emergent adverse events (AEs). Serious AEs occurred in 3.4%/6.6% and 4.0%/5.9% males/females with tofacitinib 5 mg and 10 mg two times per day. Persistence was generally similar between sexes. CONCLUSION: Tofacitinib efficacy exceeded placebo in both sexes and was comparable between sexes. Consistent with previous studies of PsA treatments, females were less likely to achieve MDA, likely due to baseline differences. Safety and time to discontinuation were generally similar between sexes. TRIAL REGISTRATION NUMBER: NCT01877668; NCT01882439; NCT01976364.

High Usability and Applicability Ratings for the New SmartClic®/ClicWise® Injection Device: Evidence from a Health Care Professional Opinion Study.

INTRODUCTION: The SmartClic®/ClicWise® autoinjector is a new reusable, multi-use, single-patient device for the administration of subcutaneously administered biologics in the treatment of chronic conditions, including rheumatoid arthritis. The device will be used in conjunction with a mobile application (app). The aim of this study was to collect feedback on the usability, functionality, and applicability of the device and the companion app from health care professionals (HCPs) who perform injections as part of their role and care for patients with rheumatic conditions. METHODS: The study was conducted from September to October 2020 in Germany. HCPs participated in a training session for the device and gained experience by performing simulated injections with water. Following the simulations, HCPs answered questions on the ease of use, feature design, effectiveness, and injection speed of the SmartClic/ClicWise device and estimate the patient training time required. They also answered questions on the functionality of the proposed app after attending a storyboard presentation. Responses were recorded as multiple-choice answers, Likert scale ratings (seven-point scale), or open-ended comments. The mean, median, and mode scores were recorded. RESULTS: Twenty-five HCPs (mean age, 38.2 years; females, n = 22 [88%]; registered nurses, n = 19 [76%]) participated in the study. HCP feedback on questions related to the SmartClic/ClicWise device was positive overall, with mean scores > 4.50 across questions; mean scores < 5.00 were reported on 2/40 questions. Twenty-four of 25 participants (96%) estimated that a training time of ≤ 20 min would suffice for patients learning to use the device. Positive feedback was also reported on questions related to the companion app, with mean scores > 5.70. CONCLUSIONS: Initial feedback from HCPs on the SmartClic/ClicWise device and proposed app was generally favorable, suggesting they will provide an acceptable alternative for self-administration of biologics for patients with rheumatoid arthritis and other chronic conditions.

Effectiveness and Safety of Tofacitinib in Canadian Patients With Rheumatoid Arthritis: Primary Results From a Prospective Observational Study.

OBJECTIVE: The Canadian Tofacitinib for Rheumatoid Arthritis Observational (CANTORAL) is the first Canadian prospective, observational study assessing tofacitinib. The objective was to assess effectiveness and safety for moderate to severe rheumatoid arthritis (RA). Coprimary and secondary outcomes are reported from an interim analysis. METHODS: Patients initiating tofacitinib from October 2017 to July 2020 were enrolled from 45 Canadian sites. Coprimary outcomes (month 6) included the Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA) and remission. Secondary outcomes (to month 18) included the CDAI and the 4-variable Disease Activity Score in 28 joints (DAS28) using the erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) level to define LDA and remission; the proportions of patients achieving mild pain (visual analog scale <20 mm), and moderate (≥30%) and substantial (≥50%) pain improvements; and the proportions of patients achieving a Health Assessment Questionnaire disability index (HAQ DI) score greater or equal to normative values (≤0.25) and a HAQ DI score greater or equal to minimum clinically important difference (MCID) (≥0.22). Safety was assessed to month 36. RESULTS: Of 504 patients initiating tofacitinib, 44.4% received concomitant methotrexate. At month 6, 52.9% and 15.4% of patients were in CDAI-defined LDA and remission, respectively; a similar proportion of patients achieved outcomes by month 3 (first post-baseline assessment). By month 3, 27.2% and 41.7% of patients, respectively, were in DAS28-ESR-defined LDA and DAS28-CRP <3.2; 14.7% and 25.8% achieved DAS28-ESR remission and DAS28-CRP <2.6. By month 3, mild pain and moderate and substantial pain improvements occurred in 29.6%, 55.6%, and 42.9% of patients, respectively; 19.9% and 53.7% of patients achieved a HAQ DI score greater than or equal to normative values and a HAQ DI score greater than or equal to MCID, respectively. Outcomes were generally maintained to month 18. Incidence rates (events per 100 patient-years) for treatment-emergent adverse events (AEs), serious AEs, and discontinuations due to AEs were 126.8, 11.9, and 14.5, respectively, and AEs of special interest were infrequent. CONCLUSION: Tofacitinib was associated with early and sustained improvement in RA signs and symptoms in real-world patients. Effectiveness and safety were consistent with the established tofacitinib clinical profile.

Impact of Methotrexate Discontinuation, Interruption, or Persistence in US Patients with Rheumatoid Arthritis Initiating Tofacitinib + Oral Methotrexate Combination.

PURPOSE: Using data from real-world practice, this analysis compared outcomes in patients with rheumatoid arthritis (RA) initiating treatment with an oral Janus kinase inhibitor, tofacitinib, in combination with persistent, discontinued, or interrupted treatment with oral methotrexate (MTX). METHODS: This retrospective claims analysis (MarketScan® databases) included data from US patients with RA and at least one prescription claim for tofacitinib, dated between January 1, 2013, and April 30, 2017. Eligible patients were continuously enrolled for ≥12 months before and after treatment initiation, and initiated tofacitinib in combination with oral MTX, with at least two prescription claims for each. Patients were grouped according to treatment pattern (MTX-Persistent, MTX-Discontinued, or MTX-Interrupted). Tofacitinib treatment persistence, adherence, and effectiveness, as well as all-cause and RA-related health care costs, were assessed. FINDINGS: A total of 671 patients were eligible for inclusion; 504 (75.1%) were MTX-Persistent; 131 (19.5%), MTX-Discontinued; and 36 (5.4%), MTX-Interrupted. Rates of tofacitinib treatment persistence, adherence, and effectiveness at 12 months were similar between the MTX-Persistent and MTX-Discontinued cohorts. The percentage of patients switched from tofacitinib to another advanced disease-modifying antirheumatic drug within 12 months of tofacitinib initiation was greater in the MTX-Persistent cohort compared with that in the MTX-Discontinued cohort. RA-related health care costs at 12 months post-initiation were significantly greater in the MTX-Persistent cohort compared with those in the MTX-Discontinued cohort. IMPLICATIONS: The findings from this analysis of real-world data indicate that patients who initiate tofacitinib in combination with oral MTX may discontinue MTX and still experience outcomes similar to those in patients who persist with MTX, with lesser RA-related health care costs. These results support those from a previous clinical study on methotrexate withdrawal in patients with RA (NCT02831855).

Predictors of nonresponse to dupilumab in patients with atopic dermatitis: A machine learning analysis.

BACKGROUND: Many patients with atopic dermatitis (AD) have a suboptimal response to systemic therapy. OBJECTIVE: This study assessed predictors of nonresponse to dupilumab in patients with AD. METHODS: Data (April 2017 through June 2019) for patients aged 12 years and above with AD (International Classification of Diseases-9/10-Clinical Modification: 691.8/L20.x) who initiated dupilumab on or after April 1, 2017 (index date) were collected from an electronic health record and insurance claims database. Nonresponse indicators (dupilumab discontinuation, addition of another systemic therapy or phototherapy, addition of a high-potency topical corticosteroid, AD-related hospital visit, AD-related emergency department visit, incident skin infection) were predicted from available demographic and clinical variables using machine learning. RESULTS: Among 419 patients (mean age: 45 years), 145 (35%) experienced at least 1 indicator of nonresponse in the 6-month postindex period. In patients with at least 1 indicator, the most common was dupilumab discontinuation (47% [68/145]). Of note, this analysis could not capture nonmedical reasons for dupilumab discontinuation (eg, cost, access). The most common predictors of nonresponse were a claim for ibuprofen (in 69% of patients with a nonresponse indicator) and a Quan-Charlson Comorbidity Index value of 3 to 4 (59%). CONCLUSION: Systemic dupilumab therapy for AD can be associated with a relatively high prevalence of nonresponse indicators. Factors associated with these indicators-that is, predictors of nonresponse-may be used to optimize disease management.

Early Real-World Experience of Tofacitinib for Psoriatic Arthritis: Data from a United States Healthcare Claims Database.

INTRODUCTION: This study characterized real-world demographic and baseline clinical characteristics, as well as treatment persistence and adherence, in patients with psoriatic arthritis (PsA) who had newly initiated tofacitinib treatment. METHODS: This retrospective cohort study included patients aged 18 years or older in the IBM MarketScan™ US database with at least one tofacitinib claim (first = index) between December 14, 2017 and April 30, 2019; PsA diagnoses on/within 12 months pre-index; and no diagnoses of rheumatoid arthritis any time pre-index. Patients were continuously enrolled for 12 months pre-index and 6 months post-index, with no pre-index claims for tofacitinib. Patient demographic and clinical characteristics on the day of index, and history of advanced treatments (including tofacitinib monotherapy or combination therapy), were recorded. Outcomes at 6 months post-index included tofacitinib persistence (less than 60-day gap without tofacitinib treatment) and adherence (proportion of days covered [PDC] and medication possession ratio 80% or higher). RESULTS: Of the 10,354 patients with tofacitinib claims within the study period, 318 patients with PsA met the inclusion criteria. More than 60% of patients received tofacitinib monotherapy post-index, with a mean duration of PsA of 760.5 days at index. For patients who received tofacitinib combination therapy post-index, methotrexate was the most common concomitant conventional synthetic disease-modifying antirheumatic drug. At 6 months post-index, persistence was similar in patients receiving tofacitinib monotherapy (69.8%) versus combination therapy (73.1%); adherence (as measured by PDC ≥ 0.8) was numerically lower in patients receiving tofacitinib monotherapy (56.8%) versus combination therapy (65.5%). CONCLUSIONS: This analysis of US-based claims data described patients who had newly initiated tofacitinib treatment an average of 2 years after PsA diagnosis, with approximately two-thirds of patients receiving tofacitinib monotherapy. Observed rates of tofacitinib persistence were similar across patients who received tofacitinib monotherapy and combination therapy 6 months after initiation; adherence rates were numerically lower in patients receiving monotherapy.

Tofacitinib is a drug approved to treat patients with psoriatic arthritis (PsA) that has been shown to improve PsA symptoms and quality of life in controlled clinical trials. However, there is not much information on everyday use of tofacitinib outside of clinical trials in the USA. This study is one of the first to describe the characteristics of patients with PsA in the USA who take tofacitinib, including their typical age, sex, where they live, how long they have had PsA, and how they use tofacitinib. Use of tofacitinib included how patients followed tofacitinib prescription timings and dose (adherence) and how long they took tofacitinib for after it was prescribed (persistence). We used data collected from a US health insurance claims database (IBM MarketScan™) for patients with PsA and at least one claim for tofacitinib. In total, 318 patients were included and over 60% of them received tofacitinib therapy only (monotherapy; no conventional synthetic disease-modifying antirheumatic drug [csDMARD] therapy). For patients treated with both tofacitinib and a csDMARD (combination therapy), methotrexate was the most common drug prescribed. Six months after their first prescription of tofacitinib, around 70% of patients were still taking tofacitinib (monotherapy or combination therapy). However, a slightly lower number of patients taking tofacitinib monotherapy were taking it as originally instructed (adherence 57%), compared with those taking tofacitinib combination therapy (adherence 66%). Our results provide valuable information on the use of tofacitinib in US real-life settings outside of clinical trials and could help to improve the quality of care for patients with PsA.

Economic Burden and Healthcare Resource Use of Alopecia Areata in an Insured Population in the USA.

INTRODUCTION: Comparative data on the economic burden of alopecia areata relative to the general population are limited. The objective of this retrospective database analysis was to evaluate healthcare resource utilization and direct medical costs among patients with alopecia areata from the US payer perspective compared with matched controls. METHODS: Validated billing codes were used to identify patients with alopecia areata from the IQVIA PharMetrics Plus (2016-2018) who had continuous pharmacy and medical enrollment for 365 days both before (baseline period) and after (evaluation period) the index date. Demographic and clinical characteristics were characterized, and baseline comorbidities were assessed with the Quan Charlson Comorbidity Index. RESULTS: Using the exact matching feature from Instant Health Data, 14,340 patients with alopecia areata were matched with 42,998 control patients aged ≥ 12 years. Patients with alopecia areata had higher healthcare resource utilization and adjusted total all-cause mean medical costs versus matched controls ($8557 versus $6416; p < 0.0001), because of higher inpatient costs, emergency department visits, ambulatory visits, number of prescriptions and prescription costs, and other costs such as durable medical equipment and home healthcare. The number of inpatient visits did not significantly differ between the two groups. Mean ambulatory costs were $3640 for patients with alopecia areata and $2062 for controls, and mean pharmacy costs were $3287 and $1843, respectively (p < 0.0001 for both). Pharmacy costs related to immunologic agents represented 50.0% of the total difference in pharmacy spending between patients with alopecia areata and controls. Surgery on the integumentary system accounted for 9.5% of the total difference in ambulatory costs. CONCLUSION: Alopecia areata is associated with significant incremental healthcare resource utilization and costs relative to matched controls due to increased spending in areas such as surgical procedures and psychological and pharmacological interventions. Costs are primarily driven by ambulatory and pharmacy spending.

The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from Phase 3 trials.

BACKGROUND: Fatigue, a common symptom of rheumatoid arthritis (RA), is detrimental to health-related quality of life (HRQoL). We evaluated the impact of tofacitinib on fatigue, sleep, and HRQoL and explored associations between fatigue, related patient-reported outcomes (PROs), and disease activity in RA patients. METHODS: This post hoc analysis pooled data from three Phase 3 studies of tofacitinib (ORAL Scan; ORAL Standard; ORAL Sync) in RA patients. Patients received tofacitinib 5 or 10 mg twice daily, placebo, or adalimumab (active control; ORAL Standard only, not powered for superiority) with conventional synthetic disease-modifying antirheumatic drugs. Assessed through Month (M)12 were changes from baseline in disease activity, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Medical Outcomes Study Sleep scale (MOS-SS), and Short Form-36 Health Survey (SF-36) composite/domain scores, and proportions of patients reporting improvements from baseline in FACIT-F total and SF-36 domain scores ≥ minimum clinically important differences (MCIDs) or ≥ population normative values. Pearson correlations examined associations among PROs at M6. Treatment comparisons were exploratory, with p < 0.05 considered nominally significant. RESULTS: Generally, active treatment led to significant improvements from baseline in FACIT-F total, and MOS-SS and SF-36 composite/domain scores vs placebo, observed by M1 and maintained through M6 (last placebo-controlled time point). Through M6, more patients achieved improvements from baseline ≥ MCID and achieved scores ≥ population normative values in FACIT-F total and SF-36 domain scores with tofacitinib vs placebo. Through M12, some nominally significant improvements with tofacitinib vs adalimumab were observed. With active treatment at M6, FACIT-F scores were moderately (0.40-0.59) to highly (≥ 0.60) correlated with SF-36 composite/domain scores (particularly vitality), moderately correlated with most MOS-SS domain scores, and highly correlated with MOS-SS Sleep Problems Index I scores. Disease activity correlations were moderate with FACIT-F scores and low (0.20-0.39) to moderate with SF-36 general health domain/composite scores. CONCLUSION: Tofacitinib and adalimumab generally conferred significant, clinically meaningful improvements in fatigue, sleep, and HRQoL (including vitality) vs placebo through M6, with improvements maintained to M12. M6 correlations between FACIT-F, PROs of sleep, HRQoL, and disease activity underscore the interrelatedness of multiple PROs and disease activity in RA. TRIAL REGISTRATION: ClinicalTrials.gov NCT00847613 (registered: February 19, 2009); NCT00853385 (registered: March 2, 2009); NCT00856544 (registered: March 5, 2009).

Clinical and Humanistic Burden of Atopic Dermatitis in Europe: Analyses of the National Health and Wellness Survey.

INTRODUCTION: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease that negatively impacts overall health, quality of life (QoL), and work productivity. Prior studies on AD burden by severity have focused on moderate-to-severe disease. Here, we describe the clinical and humanistic burden of AD in Europe across all severity levels, including milder disease. METHODS: Data were analyzed from the 2017 National Health and Wellness Survey from adult respondents with AD in the EU-5 (France, Germany, Italy, Spain, and the UK). AD disease severity was defined based on self-reported assessments as "mild," "moderate," or "severe" and by Dermatology Life Quality Index (DLQI) severity bands. Self-reported outcomes for AD respondents by severity were assessed using propensity score matching. These outcomes included a wide range of selected medical/psychological comorbidities, overall QoL and functional status (EuroQol 5-Dimensions 5-Level and Short Form-36 version 2 questionnaires), and work productivity and activity impairment (Work Productivity and Activity Impairment questionnaire). RESULTS: In total, 4208 respondents with AD (mild AD, 2862; moderate AD, 1177; severe AD, 169) and 4208 respondents without AD were included in this analysis. Results showed greater burden across severity levels compared with matched non-AD controls. A higher proportion of respondents with mild-to-moderate AD, defined by DLQI severity bands, reported atopic comorbidities (P < 0.05) and a wide range of cardiac, vascular, and metabolic comorbidities, including hypertension, high cholesterol, angina, and peripheral vascular disease (P < 0.005), compared with non-AD controls. Relative to potential impacts of various medical and psychological burdens, respondents with mild-to-moderate AD reported higher activity impairment than controls (P < 0.0001). CONCLUSION: Clinical and humanistic burden was observed in European respondents with AD compared with matched non-AD controls across severity levels, with burden evident even in milder disease, highlighting the importance of improving disease management in early stages of AD.

Identification of Distinct Disease Activity Trajectories in Methotrexate-Naive Patients With Rheumatoid Arthritis Receiving Tofacitinib Over Twenty-Four Months.

OBJECTIVE: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). To better understand tofacitinib treatment responses, we used group-based trajectory modeling to investigate distinct disease activity trajectories and associated baseline variables in patients with active RA. METHODS: This post hoc analysis used data from a phase III study of methotrexate-naive patients receiving tofacitinib 5 mg twice daily. Changes in the 4-variable Disease Activity Score in 28 joints, using the erythrocyte sedimentation rate (DAS28-ESR) from baseline to month 24 were used in group-based trajectory modeling to identify distinct disease activity trajectories. Patient and disease characteristics, changes in radiographic progression and patient-reported outcomes, and safety up to month 24 were compared among trajectory groups. RESULTS: From 346 methotrexate-naive patients, 5 disease trajectory groups, defined by DAS28-ESR scores, were identified, which progressed from high disease activity (HDA) to remission (group 1, n = 28), to low disease activity (LDA) rapidly (group 2, n = 107), to moderate disease activity (group 3, n = 98), to LDA gradually (group 4, n = 46), or remained in HDA (group 5, n = 67), at month 24. At baseline, groups 1 and 2 generally had lower disease activity and more favorable patient-reported outcomes, compared with other groups. Improvements in radiographic progression and patient-reported outcomes over 24 months were generally consistent with DAS28-ESR-predicted disease activity trajectories. Adverse event rates were generally comparable across groups. CONCLUSION: Distinct phenotypic subgroups identified heterogeneity in patients with RA normally analyzed as a single population. Trajectory modeling may enable separation of clinically meaningful subsets of patients with RA, and may help optimize treatment outcomes.

Retrospective Database Analysis: Dose Escalation and Adherence in Patients Initiating Biologics for Ulcerative Colitis.

BACKGROUND: Biologic therapies are often used in patients with ulcerative colitis (UC) who are nonresponsive to conventional treatments. However, nonresponse or loss of response to biologics often occurs, leading to dose escalation, combination therapy, and/or treatment switching. We investigated real-world treatment patterns of biologic therapies among patients with UC in the USA. METHODS: This study analyzed data from the IBM® MarketScan® Commercial and Medicare Supplemental Databases (medical/pharmacy claims for >250 million patients in the USA) to identify patients with UC initiating a biologic therapy (adalimumab, infliximab, golimumab, or vedolizumab) with 12 months of follow-up post-initiation. Key measures were patient baseline characteristics, dose escalation (average maintenance dose >20% higher than label), adherence (proportion of days covered), and ulcerative colitis-related healthcare costs in the 12 months following biologic therapy initiation. RESULTS: Of 2,331 patients included in the study (adalimumab [N = 1,291], infliximab [N = 810], golimumab [N = 127], and vedolizumab [N = 103]), 28.1% used concomitant immunosuppressant therapy within 12 months post-initiation. Overall, 23.6% (adalimumab), 34.8% (infliximab), 9.9% (golimumab), and 39.2% (vedolizumab) of patients dose escalated within 12 months. Patients who dose escalated incurred USD 20,106 higher total UC-related healthcare costs over 12 months than those who did not. Adherence (covariate-adjusted proportion of days covered) ranged from 0.63 to 0.73, and 39.3% of patients discontinued within 12 months (median treatment duration = 112 days). CONCLUSION: Dose escalation was common, and incurred higher costs, in patients with UC initiating biologic therapies. Suboptimal adherence and/or discontinuation within 12 months of initiation occurred frequently, highlighting the challenges in managing these patients.

Demographic diversity of participants in Pfizer sponsored clinical trials in the United States.

The approval of new medicinal agents requires robust efficacy and safety clinical trial data demonstrated to be applicable to population subgroups. Limited data have previously been reported by drug sponsors on the topic of clinical trial diversity. In order to establish a baseline of diversity in our clinical trials that can be used by us and other sponsors, an analysis of clinical trial diversity was conducted covering race, ethnicity, sex, and age. This analysis includes Pfizer interventional clinical trials that initiated enrollment between 2011 through 2020. The data set comprises 213 trials with 103,103 US participants. The analysis demonstrated that overall trial participation of Black or African American individuals was at the US census level (14.3% vs 13.4%), participation of Hispanic or Latino individuals was below US census (15.9% vs 18.5%), and female participation was at US census (51.1% vs 50.8%). The analysis also examined the percentage of trials that achieved racial and ethnic distribution levels at or above census levels. Participant levels above census were achieved in 56.1% of Pfizer trials for Black or African American participants, 51.4% of trials for White participants, 16.0% of trials for Asian participants, 14.2% of trials for Native Hawaiian and Pacific Islander participants, 8.5% of trials for American Indian and Alaska Native participants, and 52.3% of trials for Hispanic or Latino participants. The results presented here provide a baseline upon which we can quantify the impact of our ongoing efforts to improve racial and ethnic diversity in clinical trials.

Clinical and Economic Burden of Mild-to-Moderate Atopic Dermatitis in the UK: A Propensity-Score-Matched Case-Control Study.

INTRODUCTION: The burden of mild-to-moderate atopic dermatitis (AD) in the United Kingdom (UK) is not well understood. Long-lasting AD flares may lead to systemic inflammation resulting in reversible progression from mild to more severe AD. This study aimed to assess the clinical and economic burden of mild-to-moderate AD in the UK. METHODS: AD patients were identified in the Health Improvement Network (THIN) from 2013 to 2017 and propensity score matched to non-AD controls by demographics. Patients were identified based on continuous disease activity using validated algorithms and sufficient patient status to fully validate data integrity for the entire period. Mild-to-moderate AD patients were identified by using treatment as a surrogate. Demographics, clinical characteristics and healthcare resource use (HCRU) were obtained from THIN. Literature reviews were conducted to obtain additional outcomes. A cost-of-illness model was developed to extrapolate the burden in 2017 to the UK population and in subsequent years (2018-2022). RESULTS: In 2017, the prevalence of mild-to-moderate AD in THIN was 1.28%. These patients reported higher comorbidity rates and significantly higher (p < 0.0001) HCRU, encompassing mean general practitioner visits (5.57 versus 3.59), AD-related prescriptions (5.85 versus 0.68) and total referrals (0.97 versus 0.82) versus matched non-AD controls. The model projected total HCRU and drug excess costs of €462.99M over the 5 years. The excess cost decreased to €417.35M after excluding patients on very potent topical corticosteroids, who most likely had at least moderate disease. The excess costs increased to €1.21B and €7.06B when considering comorbidity burden and productivity losses, respectively. CONCLUSION: Mild-to-moderate AD patients had higher comorbidity burden, HCRU and cost compared with matched non-AD controls. Overall, UK country-based economic burden was high given partly the high prevalence of this disease. Moreover, productivity burden and comorbidities had considerable impact on the economic burden, which further suggests the importance of optimal disease management.

Psychosocial Comorbidities and Health Status Among Adults with Moderate-to-Severe Atopic Dermatitis: A 2017 US National Health and Wellness Survey Analysis.

INTRODUCTION: Atopic dermatitis (AD) is associated with sleep difficulties, depression, and anxiety. We evaluated the relationship between these psychosocial comorbidities and health outcomes among adults with moderate-to-severe AD in the USA. METHODS: Data were analyzed from the 2017 US National Health and Wellness Survey. Respondents with a physician diagnosis of AD or eczema with moderate-to-severe AD based on a Dermatology Life Quality Index score of 6 or more were included. Generalized linear models were used to examine the relationship between psychosocial comorbidities (sleep difficulties and anxiety based on self-report, depression based on the Patient Health Questionnaire-9) and health outcomes [the 36-item Short Form Health Survey, version 2; EuroQol five-dimension, five-level; Work Productivity and Activity Impairment questionnaire; and healthcare resource utilization (HRU)]. RESULTS: Among respondents with moderate-to-severe AD (N = 1017), 56.6%, 70.7%, and 60.9% reported sleep difficulties, depression, and anxiety, respectively. These comorbidities were significantly associated with reduced physical and mental component summary scores and increased overall work impairment (P < 0.05 for all). Increased HRU was also observed. CONCLUSION: Psychosocial comorbidities were frequently reported by respondents with moderate-to-severe AD and were significantly associated with health status, work loss, and HRU.

Real-World Evidence to Contextualize Clinical Trial Results and Inform Regulatory Decisions: Tofacitinib Modified-Release Once-Daily vs Immediate-Release Twice-Daily for Rheumatoid Arthritis.

INTRODUCTION: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To provide additional clinical evidence in regulatory submissions for a modified-release (MR) once-daily (QD) tofacitinib formulation, we compared real-world adherence and effectiveness between patients initiating the MR QD formulation and patients initiating an immediate-release (IR) twice-daily (BID) formulation. METHODS: Two noninterventional cohort studies were conducted. First, adherence and two effectiveness proxies were compared between patients with RA who newly initiated tofacitinib MR 11 mg QD or IR 5 mg BID in the IBM® MarketScan® Commercial and Medicare Supplemental US insurance claims databases (March 2016-October 2018). Second, using data collected in the Corrona US RA Registry (February 2016-August 2019), two Clinical Disease Activity Index (CDAI)-based measures of effectiveness were compared between tofacitinib MR 11 mg QD and IR 5 mg BID, and against noninferiority criteria derived from placebo-controlled clinical trials of the tofacitinib IR formulation. Multiple sensitivity analyses of the registry data were conducted to reassure regulators of consistent results across different assumptions. RESULTS: In each study, approximately two-thirds of patients initiated the MR formulation. In the claims database study, improved adherence and at least comparable effectiveness were observed with tofacitinib MR vs IR over 12 months, particularly in patients without prior advanced therapy. In the registry study, the noninferiority of tofacitinib MR vs IR was demonstrated for both CDAI outcomes at ~6 months; this finding was robust across multiple sensitivity analyses. CONCLUSION: These results demonstrate the value of real-world evidence from complementary data sources in understanding the impact of medication adherence with a QD formulation in clinical practice. These analyses were suitable for regulatory consideration as an important component of evidence for the comparability of tofacitinib MR 11 mg QD vs IR 5 mg BID in patients with RA. TRIAL REGISTRATION: Claims database study: ClinicalTrials.gov identifier NCT04018001, retrospectively registered July 12, 2019. Corrona US RA Registry study: ClinicalTrials.gov identifier NCT04267380, retrospectively registered February 12, 2020.

The Economic and Psychosocial Comorbidity Burden Among Adults with Moderate-to-Severe Atopic Dermatitis in Europe: Analysis of a Cross-Sectional Survey.

INTRODUCTION: Atopic dermatitis (AD) is a common inflammatory disease of the skin, which may have a substantial impact on patients' health-related quality of life (HRQoL). The aim of this study was to quantify the economic burden (direct and indirect costs) of moderate-to-severe AD and evaluate the prevalence and impact of psychosocial comorbidities among patients in the European Union-5 (France, Germany, Italy, Spain, and the UK). METHODS: Data were analyzed from the 2017 EU5 National Health and Wellness Survey. Respondents with a physician diagnosis of AD/eczema who were considered to have moderate-to-severe AD based on a Dermatology Life Quality Index (DLQI) score ≥ 6 were included. Direct costs, indirect costs, and psychosocial comorbidities (sleep difficulties and anxiety based on self-report, depression based on the Patient Health Questionnaire-9) were reported descriptively. Generalized linear models were used to examine the relationship between psychosocial comorbidities and health outcomes (the Short Form-36 version 2 [SF-36v2], EuroQoL 5-dimension 5-level, Work Productivity and Activity Impairment questionnaire, and healthcare resource utilization). RESULTS: Overall, 1014 patients were included in the analysis. Total annual direct costs ranged from €2242 to €6924 and total annual indirect costs ranged from €7277 to €14,236, depending on the level of disease severity. Sleep difficulties, anxiety, and depression were reported by 61.6%, 52.7%, and 75.8% of patients, respectively. These comorbidities were significantly associated with reduced physical and mental component summary scores from SF-36v2 and increased overall work impairment (p < 0.05 for all). CONCLUSIONS: A significant economic burden was observed for patients with moderate-to-severe AD. Sleep difficulties, depression, and anxiety were observed in more than half of moderate-to-severe AD patients and were significantly associated with decrements in HRQoL and with work-related impairment. Reducing the burden of these psychosocial comorbidities in AD could have significant benefit to patients and society.

Efficacy of tofacitinib in reducing pain in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis.

OBJECTIVE: To describe the efficacy of tofacitinib in reducing pain in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) in a post-hoc analysis of randomised controlled trials. METHODS: Data were collected from patients in seven tofacitinib studies: six phase III (four RA, two PsA) and one phase II study (AS), and grouped into five analysis populations based on rheumatic disease diagnosis and category of prior inadequate response (IR) to treatment: conventional synthetic disease-modifying antirheumatic drugs-IR (RA and PsA), tumour necrosis factor inhibitors-IR (RA and PsA), or non-steroidal anti-inflammatory drugs-IR (AS). Only patients who received tofacitinib 5 or 10 mg twice daily or placebo were included. Pain assessments included: Patient's Assessment of Arthritis Pain, Short-Form Health Survey 36v2 Question (Q)7 and Bodily Pain domain, Ankylosing Spondylitis Quality of Life Q9 and Q14, EuroQol Five Dimensions Pain/Discomfort dimension and Bath Ankylosing Spondylitis Disease Activity Index Q2 and Q3. Data were reported to month 6 (placebo to month 3) in the RA and PsA populations, and week 12 (tofacitinib and placebo) in the AS population. RESULTS: Overall, 3330 patients were included in this analysis. In the RA and PsA populations, pain improvements in tofacitinib-treated patients compared with placebo were observed at the earliest time point assessed and at month 3 (maintained to month 6). In the AS population, pain improvements compared with placebo were observed at week 12. CONCLUSION: Tofacitinib was associated with rapid and sustained improvements across multiple pain measures in patients with inflammatory rheumatic musculoskeletal diseases.

Treatment Mode Preferences in Rheumatoid Arthritis: Moving Toward Shared Decision-Making.

PURPOSE: Current knowledge of the reasons for patients' preference for rheumatoid arthritis (RA) treatment modes is limited. This study was designed to identify preferences for four treatment modes, and to obtain in-depth information on the reasons for these preferences. PATIENTS AND METHODS: In this multi-national, cross-sectional, qualitative study, in-depth interviews were conducted with adult patients with RA in the United States, France, Germany, Italy, Spain, Switzerland, the United Kingdom, and Brazil. Patients' strength of preference was evaluated using a 100-point allocation task (0-100; 100=strongest) across four treatment modes: oral, self-injection, clinic-injection, and infusion. Qualitative descriptive analysis methods were used to identify, characterize, and summarize patterns found in the interview data relating to reasons for these preferences. RESULTS: 100 patients were interviewed (female, 75.0%; mean age, 53.9 years; mean 11.6 years since diagnosis). Among the four treatment modes, oral administration was allocated the highest mean (standard deviation) preference points (47.3 [33.1]) and was ranked first choice by the greatest percentage of patients (57.0%), followed by self-injection (29.7 [27.7]; 29.0%), infusion (15.4 [24.6]; 16.0%), and clinic-injection (7.5 [14.1]; 2.0%). Overall, 56.0% of patients had a "strong" first-choice preference (ie, point allocation ≥70); most of these patients chose oral (62.5%) vs self-injection (23.2%), infusion (10.7%), or clinic-injection (3.6%). Speed and/or ease of administration were the most commonly reported reasons for patients choosing oral (52.6%) or self-injection (55.2%). The most common reasons for patients not choosing oral or self-injection were not wanting to take another pill (37.2%) and avoiding pain due to needles (46.5%), respectively. CONCLUSION: These data report factors important to patients regarding preferences for RA treatment modes. Patients may benefit from discussions with their healthcare professionals and/or patient support groups, regarding RA treatment modes, to facilitate shared decision-making.