Publications by authors named "Joseph C Cappelleri"

242 Publications

Does scrolling affect measurement equivalence of electronic patient-reported outcome measures (ePROM)? Results of a quantitative equivalence study.

J Patient Rep Outcomes 2021 Feb 27;5(1):23. Epub 2021 Feb 27.

Signant Health, Blue Bell, USA.

Background: Scrolling is a perceived barrier in the use of bring your own device (BYOD) to capture electronic patient reported outcomes (ePROs). This study explored the impact of scrolling on the measurement equivalence of electronic patient-reported outcome measures (ePROMs) in the presence and absence of scrolling.

Methods: Adult participants with a chronic condition involving daily pain completed ePROMs on four devices with different scrolling properties: a large provisioned device not requiring scrolling; two provisioned devices requiring scrolling - one with a "smart-scrolling" feature that disabled the "next" button until all information was viewed, and a second without this feature; and BYOD with smart-scrolling. The ePROMs included were the SF-12, EQ-5D-5L, and three pain measures: a visual analogue scale, a numeric response scale and a Likert scale. Participants completed English or Spanish versions according to their first language. Associations between ePROM scores were assessed using intraclass correlation coefficients (ICCs), with lower bound of 95% confidence interval (CI) > 0.7 indicating comparability.

Results: One hundred fifteen English- or Spanish-speaking participants (21-75y) completed all four administrations. High associations between scrolling and non-scrolling were observed (ICCs: 0.71-0.96). The equivalence threshold was met for all but one SF-12 domain score (bodily pain; lower 95% CI: 0.65) and two EQ-5D-5L item scores (pain/discomfort, usual activities; lower 95% CI: 0.64/0.67). Age, language, and device size produced insignificant differences in scores.

Conclusions: The measurement properties of PROMs are preserved even in the presence of scrolling on a handheld device. Further studies that assess scrolling impact over long-term, repeated use are recommended.
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http://dx.doi.org/10.1186/s41687-021-00296-zDOI Listing
February 2021

Ulcerative Colitis Narrative Global Survey Findings: The Impact of Living With Ulcerative Colitis-Patients' and Physicians' View.

Inflamm Bowel Dis 2021 Feb 2. Epub 2021 Feb 2.

Liverpool Hospital, South Western Sydney Clinical School, University of New South Wales, Ingham Institute of Applied Medical Research, Liverpool, New South Wales, Australia.

Background: The Ulcerative Colitis (UC) Narrative is a global patient and physician survey aimed at identifying the impact of UC and comparing and contrasting perceptions of UC burden and management approaches.

Methods: Surveys of patients with UC (self-reported diagnosis; n = 2100) and physicians (n = 1254) were completed across 10 countries by The Harris Poll between August 2017 and February 2018. Questionnaires covered multiple aspects of UC, including diagnosis, treatment, and impact on patient quality of life, in addition to standard demographic information. Descriptive statistics are reported.

Results: The majority of patients (82%) had moderate to severe UC (based on medication history; those who had only ever taken 5-aminosalicylates were excluded); 67% described their UC as controlled with few to no symptoms. On average, patients experienced 4.3 flares (standard deviation, 7.4) in the past year. Diagnostic delay was on average 2.0 years (standard deviation, 5.4); 42% of patients waited ≥1 year. Most patients (65%) felt that UC controlled their life rather than them controlling their disease. Because of the fear of repercussions, many patients had not disclosed their UC to their employer. Discussion of the emotional impact of UC during routine appointments was less of a priority for physicians, compared with patients.

Conclusions: The data from this global survey highlight that patients with UC experience diagnostic delay, poor disease control, and adverse impact on their quality of life. Patients report UC to be a mentally exhausting condition; however, emotional and mental health issues are infrequently discussed at routine appointments.
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http://dx.doi.org/10.1093/ibd/izab016DOI Listing
February 2021

Cost-effectiveness of tofacitinib compared with infliximab, adalimumab, golimumab, vedolizumab and ustekinumab for the treatment of moderate to severe ulcerative colitis in Germany.

J Med Econ 2021 Jan-Dec;24(1):279-290

Pfizer Inc, New York, NY, USA.

Objectives: Tofacitinib is an oral, small molecule Janus kinase (JAK) inhibitor for the treatment of ulcerative colitis (UC). This study assessed the cost-effectiveness of tofacitinib versus other available treatments for patients with moderate to severe UC following an inadequate response to conventional treatment and who are either naïve to or have failed previous biologics in Germany.

Methods: A Markov cohort model was developed to evaluate the differences in long-term costs and outcomes between tofacitinib and its comparators from the perspective of German statutory health insurance (SHI) for patients either naïve or exposed to biologics. Tofacitinib was compared to infliximab, infliximab biosimilar, adalimumab, adalimumab biosimilar, golimumab, vedolizumab, ustekinumab, and conventional therapy. Health states modeled were remission, treatment response, active UC, and post-colectomy. Patients not responding to treatment could switch to a different treatment. Treatment efficacy for induction and maintenance phases were assessed by a systematic literature review (SLR) and network meta-analysis (NMA). The model included costs associated with drug administration, adverse events, and medical resource use. Extensive deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted.

Results: Over a life-time horizon, patients treated with tofacitinib gained 0.035-0.083 quality-adjusted life-years (QALYs) and had direct cost savings to the SHI of €4,228-€17,184 compared to biologic treatments other than adalimumab biosimilar. When compared to adalimumab biosimilar, treatment with tofacitinib resulted in an incremental cost-effectiveness ratio (ICER) of €17,497 per QALY gained and can be considered a cost-effective alternative. Compared with conventional therapy, tofacitinib resulted in a lower ICER than all other biologics. The DSA showed that the model results were most influenced by differences in treatment efficacy. The PSA suggested confidence in the base-case results considering uncertainty around parameters.

Conclusions: The results of this economic model suggest tofacitinib is a cost-effective treatment option for patients with moderate to severe UC in Germany.
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http://dx.doi.org/10.1080/13696998.2021.1881323DOI Listing
January 2021

Effects of dose titration on adherence and treatment duration of pregabalin among patients with neuropathic pain: A MarketScan database study.

PLoS One 2021 20;16(1):e0242467. Epub 2021 Jan 20.

Department of Health Economics and Outcomes Research, Pfizer Inc, New York, NY, United States of America.

Objective: To examine pregabalin dose titration and its impact on treatment adherence and duration in patients with neuropathic pain (NeP).

Methods: MarketScan database (2009-2014) was used to extract a cohort of incident adult pregabalin users with NeP who had at least 12 months of follow-up data. Any dose augmentation within 45 days following the first pregabalin claim was defined as dose titration. Adherence (measured by medication possession ratio/MPR) and persistence (measured as the duration of continuous treatment) were compared between the cohorts with and without dose titration. Logistic regressions and Cox proportional hazards models were used to identify the factors associated with adherence (MPR ≥ 0.8) and predictors of time to discontinuation.

Results: Among the 5,186 patients in the analysis, only 18% of patients had dose titration. Patients who had dose titration were approximately 2.6 times as likely to be adherent (MPR ≥ 0.8) (odds ratio = 2.59, P < 0.001) than those who did not have dose titration. Kaplan-Meier analysis shows that the time to discontinuation or switch was significantly longer among patients who had dose titration (4.99 vs. 4.04 months, P = 0.009).

Conclusions: Dose titration was associated with improved treatment adherence and persistence among NeP patients receiving pregabalin. The findings will provide valuable evidence to increase physician awareness of dose recommendations in the prescribing information and to educate patients on the importance of titration and adherence.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242467PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816971PMC
January 2021

Development and Content Validation of Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) in Adolescents and Adults with Moderate-to-Severe AD.

Dermatol Ther (Heidelb) 2021 Feb 3;11(1):221-233. Epub 2021 Feb 3.

Pfizer Inc., New York, NY, USA.

Introduction: Most patient-reported outcome (PRO) instruments that measure atopic dermatitis (AD) symptoms do not have sufficient documented evidence of content validity to satisfy regulatory agency guidance for inclusion in product-labelling claims in the USA or Europe. The objective of this study was to develop a PRO instrument in accordance with regulatory agency guidance to assess daily AD symptoms during the course of therapy and to establish its content validity and psychometric properties.

Methods: The Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) daily diary was developed based on qualitative interviews with US adolescents and adults with mild-to-severe AD. Content validity, test-retest reliability, internal consistency reliability, clinically important difference, clinically important responder, convergent validity, and known-group validity were evaluated using correlational and regression methods from phase 2b data from US adults with moderate-to-severe AD who were treated with abrocitinib.

Results: Patient interviews conducted with US adolescents and adults with mild-to-severe AD identified 11 relevant symptoms (itch, dryness, redness, flaking, discolouration, pain, bleeding, cracking, bumps, swelling, and weeping/oozing) for inclusion in the PSAAD instrument. All PSAAD psychometric parameters were acceptable based on phase 2b data from US adults with moderate-to-severe AD. Convergent validity and known-group validity were confirmed by significant correlations between PSAAD and six other PRO measures (r = 0.24-0.91, all p ≤ 0.01) and Dermatology Life Quality Index category (p ≤ 0.0001), respectively.

Conclusions: Evidence supports the PSAAD instrument validity, reliability, responsiveness and definitions of clinically important changes/differences for adults with moderate-to-severe AD.
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http://dx.doi.org/10.1007/s13555-020-00474-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859139PMC
February 2021

Multimodal Treatment Patterns for Osteoarthritis and Their Relationship to Patient-Reported Pain Severity: A Cross-Sectional Survey in the United States.

J Pain Res 2020 23;13:3415-3425. Epub 2020 Dec 23.

Real World Research, Adelphi Real World, Bollington, Cheshire, UK.

Purpose: The purpose of this study was to assess how patient-reported pain is related to osteoarthritis (OA) treatment patterns in routine clinical practice.

Patients And Methods: Data were collected between February and May 2017 from 153 United States (US) primary care physicians, rheumatologists, and orthopedic surgeons. Each invited up to nine consecutive patients to rate their OA pain in the last week. Physicians provided demographic, clinical, and treatment information for patients, including nonpharmacologic therapies ever recommended, currently recommended over-the-counter (OTC) medications, and currently and ever prescribed medications for the management of OA. Findings for patients with mild (0─3), moderate (4─6), and severe current pain (7─10) were compared using appropriate statistics.

Results: Among the 841 patients (61% female; mean 65 years; 57% knee OA), 45% reported mild, 36% moderate, and 19% severe current OA pain. Current treatment modalities differed by pain severity (<0.05). Most patients (70%) had been recommended nonpharmacologic therapy and 40% were currently recommended OTC medications. More patients with moderate (81%) or severe pain (78%) currently received prescription medications, with or without nonpharmacologic therapy, versus those with mild pain (67%). Overall, 47% of patients currently received just one prescription drug, while 49% had received one prescription drug ever. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most common current (58%) and ever received (88%) prescriptions. Current NSAID prescriptions were not associated with pain severity. Acetaminophen recommendations, opioid prescriptions (current and ever), and multiple prescription medications tried were numerically highest in the severe pain group (all <0.05 by pain severity). In all groups, >80% of treatment switches were due to lack of efficacy.

Conclusion: Real-life treatment patterns for OA in the US are significantly associated with current patient-reported pain. Combining nonpharmacologic and pharmacologic treatments is common but higher pain ratings are associated with multiple failed prescription treatments. Current use of acetaminophen and opioids, but not NSAIDs, increases alongside pain severity.
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http://dx.doi.org/10.2147/JPR.S285124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767791PMC
December 2020

Clinical and Economic Burden of Pediatric Mild-to-Moderate Atopic Dermatitis: A Population-Based Nested Case-Control Study in Sweden.

Dermatol Ther (Heidelb) 2021 Feb 18;11(1):161-172. Epub 2020 Dec 18.

Inflammation and Immunology, Pfizer Inc, Collegeville, PA, USA.

Introduction: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition characterized by pruritic, eczematous lesions. Recent evidence suggests that AD may be a systemic disorder, implying that management of this disease extends beyond merely controlling symptoms associated with AD. Even though this disease is highly prevalent in children and patients typically present with mild-to-moderate symptoms, the disease burden is not well established.

Methods: A large, retrospective cohort study of Swedish population data was conducted to compare the clinical burden in terms of healthcare resource use and direct medical costs for pediatric mild-to-moderate (pM2M) AD patients (≤ 14 years of age, N = 87,721) with matched controls. The burden of a severe AD cohort was also evaluated. Severity of AD was defined by treatment usage and systemic treatment was used as a proxy for severe AD. A robust approach was used by including any type of secondary care visits known to be more common in AD patients than in the general population; however, data for primary care visits were not available.

Results: For healthcare resource use, the incidence rate ratio (pM2M AD versus reference cohort) of secondary care visits ranged from 1.56 to 2.35 during each of 5 years after AD onset (all p < 0.001), with largest differences seen in years 1-2. The average direct medical cost (SD) was €1111 (3416) and €524 (2446) in the pM2M AD and reference cohorts, respectively. The corresponding estimate in the severe AD cohort was €1906 (7067). Including all secondary care visits and pharmacy-dispensed medications, the pM2M AD cohort was shown to have an additional €118.9 million in direct medical costs over 5 years compared with the reference cohort.

Conclusions: This study shows significant clinical and economic burden of pM2M AD with important secondary care resource utilization, suggesting a need for further research to increase treatment options and improve the management of these patients.
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http://dx.doi.org/10.1007/s13555-020-00470-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859158PMC
February 2021

Tofacitinib Treatment Safety in Moderate to Severe Ulcerative Colitis: Comparison of Observational Population Cohort Data From the IBM MarketScan® Administrative Claims Database With Tofacitinib Trial Data.

Inflamm Bowel Dis 2020 Dec 16. Epub 2020 Dec 16.

Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We aimed to estimate the overall incidence of safety events in patients with UC in a real-life population cohort for comparison with the tofacitinib UC clinical trial program.

Methods: Clinical trial-like criteria were applied to an IBM MarketScan® claims database population-based cohort (n = 22,967) of patients with UC (October 2010 to September 2015) to identify a UC trial-like cohort treated with tumor necrosis factor inhibitors (TNFi; n = 6366) to compare with the tofacitinib UC clinical trial cohort (n = 1157).

Results: Incidence rates (events per 100 patient-years; [95% confidence interval]) in the UC trial-like cohort were as follows: serious infections, 3.33 (2.73-4.02); opportunistic infections (OIs; excluding herpes zoster [HZ]), 1.45 (1.06-1.93); HZ, 1.77 (1.34-2.29); malignancies (excluding nonmelanoma skin cancer [NMSC]), 0.63 (0.43-0.90); NMSC, 1.69 (1.35-2.10); major adverse cardiovascular events (MACE), 0.51 (0.31-0.79); pulmonary embolism (PE), 0.54 (0.30-0.89); deep vein thrombosis (DVT), 1.41 (1.00-1.93); and gastrointestinal perforations, 0.31 (0.16-0.54). Compared with the UC trial-like cohort, tofacitinib-treated patients had numerically lower incidence rates for serious infections (1.75 [1.27-2.36]), OIs (excluding HZ; 0.16 [0.04-0.42]), NMSC (0.78 [0.47-1.22]), PE (0.16 [0.04-0.41]), and DVT (0.04 [0.00-0.23]), and a higher rate for HZ (3.57 [2.84-4.43]); rates for malignancies (excluding NMSC), MACE, and gastrointestinal perforations were similar.

Conclusions: When acknowledging limitations of comparing claims data with controlled clinical trial data, incidence rates for HZ among TNFi-treated patients in the UC trial-like cohort were lower than in the tofacitinib UC clinical trial cohort; rates for serious infections, OIs, NMSC, PE, and DVT were numerically higher.

Clinicaltrials.gov: NCT00787202, NCT01465763, NCT01458951, NCT01458574, NCT01470612.
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http://dx.doi.org/10.1093/ibd/izaa289DOI Listing
December 2020

Budget Impact Analysis of Gemtuzumab Ozogamicin for the Treatment of CD33-Positive Acute Myeloid Leukemia.

Pharmacoeconomics 2021 Jan 25;39(1):121-131. Epub 2020 Nov 25.

RTI Health Solutions, Research Triangle Park, NC, USA.

Background: Gemtuzumab ozogamicin (GO) was approved in 2017 in the US for the treatment of adults with newly diagnosed CD33-positive (CD33+) acute myeloid leukemia (AML), and adults and pediatric patients with CD33+ relapsed/refractory (R/R) AML.

Objective: The aim of this study was to estimate the budgetary impact of introducing GO to a 1-million-member US health plan over a 5-year period.

Methods: We developed models to estimate the impact of introducing GO in combination with conventional induction chemotherapy or as monotherapy for newly diagnosed AML, and as monotherapy for R/R AML. Models were built using data on drug costs and treatment-related outcomes obtained from published clinical trials and other publicly available sources. Results were reported on a per member/per year and per member/per month (PMPM) basis.

Results: Base-case results of the newly diagnosed model indicated that the addition of GO in the combination setting reduced the overall budget of a 1-million-member health plan. The estimated net cost (US$) savings ranged from $72,969 ($0.006 PMPM) in year 1 to $745,426 ($0.062 PMPM) in year 5. In the monotherapy setting, GO was associated with increased net costs ranging from $4118 (0.0003 PMPM) in year 1 to $31,885 ($0.003 PMPM) in year 5. Base-case results of the R/R AML model demonstrated increased net costs that ranged from $17,326 ($0.001 PMPM) in year 1 to $46,163 ($0.004 PMPM) in year 5. Scenario analyses in all settings indicated the budget impact was not overly sensitive to the selected input assumptions, with the exception of the scenario considering only the pharmacy budget impact in the combination setting.

Conclusions: The introduction of GO for newly diagnosed and R/R AML would have a minimal impact on the budget of a US health plan and could result in cost savings in the combination therapy setting for newly diagnosed AML.
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http://dx.doi.org/10.1007/s40273-020-00976-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790788PMC
January 2021

Pain severity and healthcare resource utilization in patients with osteoarthritis in the United States.

Postgrad Med 2021 Jan 4;133(1):10-19. Epub 2020 Dec 4.

Real World Research, Adelphi Real World , Bollington, UK.

Objective: To evaluate healthcare resource utilization (HCRU) by osteoarthritis (OA) pain severity.

Methods: Cross-sectional surveys of US physicians and their patients were conducted between February and May 2017. Using the Numeric Rating Scale, patients were classified by self-reported pain intensity in the last week into mild (0-3), moderate (4-6), and severe (7-10) cohorts. Parameters assessed included clinical characteristics, HCRU, and current caregiver support. Descriptive statistics were obtained, and analysis of variance and chi-square tests were performed.

Results: Patients (n = 841) were mostly female (60.9%) and white (77.8%), with mean age of 64.6 years. Patients reported mild (45.4%), moderate (35.9%), and severe (18.7%) OA pain. Mean number of affected joints varied by pain severity (range mild: 2.7 to severe: 3.6; < 0.0001). Pain severity was associated with an increased number of physician-reported and patient-reported overall healthcare provider visits (HCPs; both < 0.001). As pain increased, patients reported an increased need for mobility aids, accessibility modifications to homes, and help with daily activities due to functional disability. The number of imaging tests used to diagnose OA was similar across pain severity but varied when used for monitoring (X-rays: < 0.0001; computerized tomography scans: < 0.0447). Hospitalization rates for OA were low but were significantly associated with pain severity (mild: 4.9%; severe: 11.5%). Emergency department visits were infrequent but increasing pain severity was associated with more prior and planned surgeries.

Conclusion: Greater current pain was associated with more prior HCRU including imaging for monitoring progression, HCP visits including more specialty care, hospitalizations, surgery/planned surgery, and loss of independence due to functional disability. Yet rates of hospitalizations and X-ray use were still sizable even among patients with mild pain. These cross-sectional findings warrant longitudinal assessment to further elucidate the impact of pain on HCRU.
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http://dx.doi.org/10.1080/00325481.2020.1841988DOI Listing
January 2021

Ulcerative Colitis Narrative Global Survey Findings: Communication Gaps and Agreements Between Patients and Physicians.

Inflamm Bowel Dis 2020 Oct 15. Epub 2020 Oct 15.

Department of Internal Medicine, University Hospital Schleswig-Holstein, Kiel, Germany.

Background: The Ulcerative Colitis (UC) Narrative global surveys examined patient and physician perspectives on living with UC and tried to identify gaps in optimal care. Questions explored patient-physician interactions, UC management goals, and resources for improving communication.

Methods: Questionnaires were conducted across 10 countries, covering aspects of UC including diagnosis, treatment, and impact on patient quality of life, in addition to standard demographic information. Descriptive statistics were calculated.

Results: Globally, 2100 patients and 1254 physicians were surveyed (from August 2017 to February 2018). Results showed 85% of patients were satisfied with the communication they had with their physician, including discussions relating to symptoms (86%) and medication options (81%). However, 72% of patients wished for more information and support at initial diagnosis, and 48% did not feel comfortable talking to their physician about emotional concerns. Most patients (71%) set UC management goals with their physician. Both patients (63%) and physicians (79%) wished for longer appointments. Although 84% of physicians believed patient advocacy organizations to be important in UC management, more than half (54%) never discussed them with patients.

Conclusions: These survey results highlight overall patient satisfaction with patient-physician communication but emphasize areas for improvement, such as patient desire to have more information earlier in their disease course. There is an unmet need for better information, materials, and support. Physicians need to consider which of the available tools and resources can help patients talk more openly, and accurately, because informed patients are more likely to engage with physicians in a shared decision-making process.
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http://dx.doi.org/10.1093/ibd/izaa257DOI Listing
October 2020

Correction to: Crisaborole Ointment, 2%, for Treatment of Patients with Mild-to-Moderate Atopic Dermatitis: Systematic Literature Review and Network Meta-Analysis.

Dermatol Ther (Heidelb) 2020 Dec;10(6):1441-1444

Global Biometrics and Data Management (Statistics), Pfizer Inc., Groton, USA.

The authors would like to replace 2 small sections of the published manuscript that refer to a qualitative review of safety data for included studies (together with an associated safety table), to provide some further clarifications on these safety data and to include some quantitative updates for rates.
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http://dx.doi.org/10.1007/s13555-020-00452-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649182PMC
December 2020

Quantifying patient preferences for systemic atopic dermatitis treatments using a discrete-choice experiment.

J Dermatolog Treat 2020 Nov 2:1-10. Epub 2020 Nov 2.

Pfizer Inc, New York, NY, USA.

Objectives: To identify meaningful treatment attributes and quantify patient preferences for attributes of systemic atopic dermatitis (AD) treatments.

Materials And Methods: Qualitative interviews were conducted with adults with moderate-to-severe AD ( = 21) to identify AD treatment attributes that patients consider most important and inform attribute selection for an online discrete-choice experiment (DCE) survey administered to patients in the United States with moderate-to-severe AD. Participants identified probability of clear/almost clear skin at 16 weeks, time to itch relief, mode of administration, and safety risks as very important. DCE data were analyzed using a random-parameters logit model to estimate the relative importance of treatment attributes and maximum acceptable risk.

Results: A total of 320 respondents completed the DCE survey (74% female; mean age, 35 years). Annual risk of malignancy was the most important attribute, followed by mode of administration, probability of clear skin at 16 weeks, and time to onset of itch relief. Respondents preferred daily oral treatment over injectable treatment. Respondents were willing to accept increases in adverse event risks for improvements in efficacy and mode of administration.

Conclusion: The findings of this study can help inform joint patient-physician decision making in managing moderate-to-severe AD.
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http://dx.doi.org/10.1080/09546634.2020.1832185DOI Listing
November 2020

Network Meta-Analysis of Tofacitinib, Biologic Disease-Modifying Antirheumatic Drugs, and Apremilast for the Treatment of Psoriatic Arthritis.

Curr Ther Res Clin Exp 2020 12;93:100601. Epub 2020 Aug 12.

Pfizer Inc, Groton, Connecticut.

Background: Tofacitinib and other new treatments approved for use in psoriatic arthritis have only recently been included in psoriatic arthritis treatment guidelines, and studies evaluating the relative efficacy of available therapies are important to inform treatment decisions by healthcare professionals.

Objective: To perform a network meta-analysis to evaluate the efficacy and safety profiles of tofacitinib, biologic disease-modifying antirheumatic drugs (bDMARDs), and apremilast in patients with psoriatic arthritis naïve to tumor necrosis factor inhibitor therapy (TNFi-naïve) or with an inadequate response (TNFi-IR).

Methods: A systematic literature review used searches of MEDLINE, Embase, and The Cochrane Library on October 9, 2017. Randomized controlled trials including adult patients with psoriatic arthritis receiving treatment administered as monotherapy or with conventional synthetic DMARDs were selected. Efficacy outcomes included American College of Rheumatology 20 response, change from baseline in Health Assessment Questionnaire-Disability Index, ≥75% improvement in Psoriasis Area and Severity Index, and change from baseline in Dactylitis Severity Score and Leeds Enthesitis Index. Treatment effects were evaluated during placebo-controlled phases, using a binomial logit model for binary outcomes and a normal identify link model for other outcomes. Discontinuations due to adverse events and serious infection events were assessed as safety outcomes.

Results: The network meta-analysis included 24 published randomized controlled trials, of which 13 enrolled TNFi-naïve patients only, 3 enrolled TNFi-IR patients only, and 8 enrolled both TNFi-naïve and TNFi-IR patients. Placebo-controlled treatment durations ranged from 12 to 24 weeks. Indirect comparisons showed tofacitinib 5 and 10 mg BID to have similar efficacy compared with most bDMARDs and apremilast in improving joint symptoms (based on American College of Rheumatology 20 response), and with some bDMARDs in improving skin symptoms (based on Psoriasis Area and Severity Index) (tofacitinib 10 mg BID only in TNFi-IR) in patients with psoriatic arthritis who were TNFi-naïve or TNFi-IR. Results also showed that, compared with placebo, the improvement in physical functioning (based on Health Assessment Questionnaire-Disability Index) with tofacitinib 5 and 10 mg BID was similar to that observed with most bDMARDs and apremilast in TNFi-naïve patients, and similar to that observed with all bDMARDs with available data in the TNFi-IR population. Improvements in Dactylitis Severity Score and Leeds Enthesitis Index scores were comparable between treatments. Tofacitinib 5 and 10 mg BID were median-ranked 8 and 15, respectively, for discontinuation due to any adverse events, and 5 and 16, respectively, for a serious infection event out of a total of 20 treatments in the network (lower numbers are more favorable).

Conclusions: Tofacitinib provides an additional treatment option for patients with psoriatic arthritis, both in patients naïve to TNFi and in those with TNFi-IR. ( 2020; 81:XXX-XXX).
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http://dx.doi.org/10.1016/j.curtheres.2020.100601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494680PMC
August 2020

Improvement in disease severity and pruritus outcomes with crisaborole ointment, 2%, by baseline atopic dermatitis severity in children and adolescents with mild-to-moderate atopic dermatitis.

Pediatr Dermatol 2020 Nov 27;37(6):1030-1037. Epub 2020 Sep 27.

Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Background/objectives: Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD). This pooled post hoc analysis of two phase 3 trials (NCT02118766, NCT02118792) assessed improvement and time to improvement in Investigator's Static Global Assessment (ISGA) and Severity of Pruritus Scale (SPS) outcomes in pediatric patients with mild-to-moderate AD.

Methods: Patients aged ≥2 years were randomly assigned 2:1 to receive twice-daily crisaborole or vehicle for 28 days. Patients aged 2-17 years were pooled for this analysis. Proportions of patients and time to achieving ISGA success (clear [0] or almost clear [1] with ≥2-grade improvement from baseline), ISGA clear/almost clear, ≥1-grade improvement in ISGA, SPS success (SPS score ≤1 with ≥1-grade improvement), or ≥1-grade improvement in SPS score were analyzed and stratified by baseline ISGA.

Results: At first postbaseline assessment (day 8), significantly higher proportions of crisaborole- than vehicle-treated patients achieved ISGA success, ISGA clear/almost clear, ≥1-grade ISGA improvement, SPS success, or ≥1-grade improvement in SPS regardless of baseline ISGA. Differences were significantly greater over time for all outcomes for patients with moderate baseline ISGA and numerically greater for those with mild baseline ISGA. Median times to ISGA and SPS outcomes were shorter for crisaborole versus vehicle.

Conclusion: Improvement in ISGA and SPS outcomes were observed with crisaborole in pediatric patients with mild-to-moderate baseline AD.
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http://dx.doi.org/10.1111/pde.14328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756882PMC
November 2020

Living with Ulcerative Colitis Study (LUCY) in England: a retrospective study evaluating healthcare resource utilisation and direct healthcare costs of postoperative care in ulcerative colitis.

BMJ Open Gastroenterol 2020 09;7(1)

Patient Health Impact, Pfizer Inc, New York, New York, USA.

Objective: Ulcerative colitis (UC) is a lifelong, relapsing-remitting disease. Patients non-responsive to pharmacological treatment may require a colectomy. We estimated pre-colectomy and post-colectomy healthcare resource utilisation (HCRU) and costs in England.

Design/method: A retrospective, longitudinal cohort study indexing adult patients with UC undergoing colectomy (2009-2015), using linked Clinical Practice Research Datalink/Hospital Episode Statistics data, was conducted. HCRU, healthcare costs and pharmacological treatments were evaluated during 12 months prior to and including colectomy (baseline) and 24 months post-colectomy (follow-up; F-U), comparing baseline/F-U, emergency/elective colectomy and subtotal/full colectomy using descriptive statistics and paired/unpaired tests.

Results: 249 patients from 26 165 identified were analysed including 145 (58%) elective and 184 (74%) full colectomies. Number/cost of general practitioner consultations increased post-colectomy (p<0.001), and then decreased at 13-24 months (p<0.05). From baseline to F-U, the number of outpatient visits, number/cost of hospitalisations and total direct healthcare costs decreased (all p<0.01). Postoperative HCRU was similar between elective and emergency colectomies, except for the costs of colectomy-related hospitalisations and medication, which were lower in the elective group (p<0.05). Postoperative costs were higher for subtotal versus full colectomies (p<0.001). At 1-12 month F-U, 30%, 19% and 5% of patients received aminosalicylates, steroids and immunosuppressants, respectively.

Conclusion: HCRU/costs increased for primary care in the first year post-colectomy but decreased for secondary care, and varied according to the colectomy type. Ongoing and potentially unnecessary pharmacological therapy was seen in up to 30% of patients. These findings can inform patients and decision-makers of potential benefits and burdens of colectomy in UC.
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http://dx.doi.org/10.1136/bmjgast-2020-000456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497134PMC
September 2020

Are pain severity and current pharmacotherapies associated with quality of life, work productivity, and healthcare utilisation for people with osteoarthritis in five large European countries?

Clin Exp Rheumatol 2020 Sep 4. Epub 2020 Sep 4.

Pain Center, Cochin Hospital, Paris Descartes University, Paris, France.

Objectives: Although the osteoarthritis (OA) burden is well-recognised, the benefit of currently available OA pharmacological therapy is not clear. This study aimed to assess whether the impact of OA pain on health-related quality of life (HRQoL), work, and healthcare resource utilisation (HRU) differed by both pain severity and prescription medication status.

Methods: This cross-sectional study used pooled data from the 2016/2017 European National Health and Wellness Survey. Respondents with self-reported physician-diagnosed OA and pain were included. Outcomes examined included HRQoL, health utility, health status, work productivity and activity impairment, and HRU. Groups derived from self-reported pain severity and prescription medication use were compared using chi-square tests, analysis of variance, and generalised linear models controlling for socio-demographics, health behaviours, and health status.

Results: Respondents with OA (n=2417) reported mild (40.4%, of which 44.9% prescription-treated) and moderate to severe pain (59.6%, of which 54.0% prescription-treated). HRQoL, health utility, health status, and work and activity impairment were substantially worse among the moderate/severe pain prescription-treated group compared to the rest (e.g. SF-12v2 physical component score [PCS] for moderate/severe pain prescription-treated=34.5 versus mild pain prescription-treated =39.3, moderate/severe pain prescription-untreated=40.6, and mild pain prescription-untreated=45.6; p<0.01). HRU such as the mean number of emergency room visits for >6 months was higher in the prescription-treated groups (0.51-0.52, 95% CI 0.437-0.71) than the prescription-untreated groups (0.30-0.34, 95% CI 0.21-0.46; p<0.05).

Conclusions: Persons with moderate to severe OA pain treated with available prescription medications have poor health status and HRQoL and increased HRU compared to those not receiving prescription medications.
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September 2020

Network meta analysis of first-line therapy for advanced EGFR mutation positive non-small-cell lung cancer: updated overall survival.

Future Oncol 2020 Dec 1;16(36):3107-3116. Epub 2020 Sep 1.

Pfizer Inc, New York, NY 10017, USA.

To update overall survival (OS) results from a previous network meta analysis comparing the relative clinical efficacy of epidermal growth factor receptor-targeted tyrosine kinase inhibitors ( TKIs) for mutation positive (+) advanced non-small-cell lung cancer (NSCLC). A Bayesian network meta analysis was conducted using updated/mature randomized controlled trial OS results in response to first-line TKI therapies. Dacomitinib showed a numerical improvement of OS relative to other TKIs: afatinib (hazard ratio [HR]: 0.87; 95% credible interval [CrI]: 0.61-1.24), erlotinib (HR: 0.79; 95% CrI: 0.44-1.42), gefitinib (HR: 0.75; 95% CrI: 0.59-0.95) and osimertinib (HR: 0.94; 95% CrI: 0.68-1.29). Dacomitinib should be considered as a first-line treatment option for patients diagnosed with advanced + NSCLC.
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http://dx.doi.org/10.2217/fon-2020-0541DOI Listing
December 2020

Tofacitinib in Patients with Ulcerative Colitis: Inflammatory Bowel Disease Questionnaire Items in Phase 3 Randomized Controlled Induction Studies.

Inflamm Bowel Dis 2020 Aug 14. Epub 2020 Aug 14.

Inflammatory Bowel Diseases Unit, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We examined the effect of tofacitinib induction treatment on Inflammatory Bowel Disease Questionnaire (IBDQ) items in adults with moderate to severe UC.

Methods: Data were pooled from the randomized, 8‑week, double-blind, phase 3 OCTAVE Induction 1 and 2 studies. The IBDQ was self-administered by patients at baseline, week 4, and week 8, with higher scores indicating better health-related quality of life (HRQoL). Change from baseline in IBDQ items was analyzed for 10 mg of tofacitinib twice daily (BID) vs placebo using a linear mixed-effects model, with no multiplicity adjustment performed. Effect sizes were calculated. Subgroup analyses by tumor necrosis factor inhibitor (TNFi) experience were performed.

Results: Significant improvements (nominal P < 0.05) were observed in all IBDQ items with 10 mg of tofacitinib BID vs placebo at weeks 4 and 8. For the overall population, the largest treatment differences across all items were reported for "bowel movements been loose" at weeks 4 and 8, and "problem with rectal bleeding" at week 8 (mean treatment differences all 1.1; both in bowel symptoms domain). These items also showed the largest effect sizes. Treatment benefits were generally slightly numerically higher in TNFi-experienced vs TNFi-naïve patients.

Conclusions: Tofacitinib induction therapy improved all IBDQ items vs placebo in patients with UC, reflecting improvements in HRQoL, with greatest benefits reported in bowel symptoms domain items (Funded by Pfizer Inc; OCTAVE Induction 1 and OCTAVE Induction 2; ClinicalTrials.gov, NCT01465763 and NCT01458951, respectively).
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http://dx.doi.org/10.1093/ibd/izaa193DOI Listing
August 2020

POLARIS: a prospective, multicenter, noninterventional study assessing palbociclib in hormone receptor-positive advanced breast cancer.

Future Oncol 2020 Nov 13;16(31):2475-2485. Epub 2020 Aug 13.

Pfizer Inc, 235 E. 42nd Street, New York, NY 10017, USA.

This report describes the rationale, purpose and design of the POLARIS study. POLARIS is an ongoing noninterventional, prospective, multicenter study. Female and male patients in the USA and Canada diagnosed with hormone receptor-positive/HER2-negative metastatic breast cancer were enrolled in the study and treated with the cyclin-dependent kinase 4/6 inhibitor palbociclib when hormone receptor-positive/HER2-negative metastatic breast cancer was deemed to be indicated by their physician. The study will provide real-world data on palbociclib prescribing and treatment patterns in routine clinical practice, associated clinical outcomes, treatment sequencing in the advanced/metastatic setting, patient quality of life and geriatric-specific assessments. The tumor genomic landscape in relation to clinical outcomes will be explored. POLARIS will identify benefits and side effects of palbociclib across multiple lines of therapy and in discrete subsets of patients. : NCT03280303 (ClinicalTrials.gov).
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http://dx.doi.org/10.2217/fon-2020-0573DOI Listing
November 2020

A quality-adjusted survival time without symptoms or toxicities analysis of glasdegib plus low-dose cytarabine versus low-dose cytarabine as initial therapy for acute myeloid leukemia in patients who are not considered candidates for intensive chemotherapy.

Cancer 2020 Oct 22;126(19):4315-4321. Epub 2020 Jul 22.

Pharmerit - an OPEN Health Company, Bethesda.

Background: In a randomized study, glasdegib (a hedgehog inhibitor) plus low-dose cytarabine (LDAC) significantly prolonged survival in comparison with LDAC in patients with acute myeloid leukemia (AML). A quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) approach was used to evaluate comparative quality-adjusted survival.

Methods: Overall survival was partitioned into the following: time with any treatment-emergent grade 3 or higher adverse events (TOX); time without symptoms of disease progression or toxicity (TWiST); and time after treatment discontinuation due to insufficient clinical response, relapse, or death time after progression (REL). Q-TWiST was calculated by multiplying the restricted mean time in each state by respective utilities and then summing up the utility-adjusted time.

Results: At 20 months of follow-up, the survival probabilities for the glasdegib-LDAC arm and the LDAC arm were 28.2% and 7.9%, respectively. Glasdegib-LDAC patients (n = 78), in comparison with LDAC patients (n = 38), had significantly longer mean TWiST (+3.4 months; 95% confidence interval [CI], 1.8-5.2 months) and TOX (+0.8 months; 95% CI, 0.1-1.6 months) and longer but nonsignificant REL (+0.3 months; 95% CI, -1.9 to 2.3 months). Q-TWiST was 4.0 months (95% CI, 2.1-5.8 months) longer with glasdegib plus LDAC, and this translated into a 75% relative improvement in quality-adjusted survival with respect to LDAC. Results were robust to the length of follow-up (6-24 months) and remained significant when all adverse events, regardless of grade, were included.

Conclusions: These results suggest that most of the survival benefit from glasdegib plus LDAC versus LDAC alone is TWiST, and this represents added time in relatively "good" health. These results support the clinical value of glasdegib plus LDAC as initial therapy for AML in patients for whom intensive chemotherapy is not an option.
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http://dx.doi.org/10.1002/cncr.33072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540307PMC
October 2020

Costs and Treatment Patterns Among Patients with Atopic Dermatitis Using Advanced Therapies in the United States: Analysis of a Retrospective Claims Database.

Dermatol Ther (Heidelb) 2020 Aug 30;10(4):791-806. Epub 2020 Jun 30.

Pfizer Inc., Collegeville, PA, USA.

Introduction: For many, atopic dermatitis (AD) is not adequately controlled with topical regimens. This analysis examined treatment using advanced therapies and associated costs.

Methods: The IQVIA Health Plan Claims data set was analyzed. Patients aged ≥ 12 years with AD who newly initiated advanced therapy after the availability of dupilumab (March 28, 2017) and had ≥ 6 months continuous enrollment before and after their first advanced therapy claim (index date) were included. Advanced therapies included dupilumab, systemic corticosteroids (SCSs), systemic immunosuppressants (SISs), and phototherapy. A multivariate regression model was used to predict annualized follow-up healthcare costs.

Results: In total, 1980 patients were included (61.1% female; mean age, 41.2 years [SD, 17.4]; 11.3% < 18 years). Pre-index date, 65.2% of patients used topical corticosteroids (TCSs; 40.7% and 32.1% used medium and high potency, respectively). The most common advanced therapy was SCSs (N = 1453 [73.4%]; 69.2% prednisone) followed by dupilumab (N = 265 [13.4%]), SISs (N = 99 [5.0%]; 47.5% methotrexate), and phototherapy (N = 163 [8.2%]). Of patients treated with dupilumab, SISs, and phototherapy, 17.4%, 26.3%, and 14.1%, respectively, were prescribed SCSs post-index date. Overall, 62.6% of patients initiating SCSs, 49.1% initiating dupilumab, 64.6% initiating SISs, and 36.2% initiating phototherapy were prescribed TCSs post-index date. Mean annualized total costs (SD) post-index date were $20,722 ($47,014): $11,196 ($41,549) in medical costs ($7973 [$35,133] in outpatient visit costs) and $9526 ($21,612) in pharmacy costs. Mean annualized total cost (SD) varied significantly (P < 0.05) by index treatment: dupilumab, $36,505 ($14,028); SCSs, $17,924 ($49,019); SISs, $24,762 ($47,583); phototherapy, and $17,549 ($57,238).

Conclusions: Switching to combination therapy with SCSs and TCSs was common within 6 months of initiating advanced therapy in patients with AD. Patients also incurred significant pharmacy and outpatient costs. These results highlight the difficulty of managing AD with these existing treatment options.
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http://dx.doi.org/10.1007/s13555-020-00413-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367964PMC
August 2020

Treatment Mode Preferences in Psoriatic Arthritis: A Qualitative Multi-Country Study.

Patient Prefer Adherence 2020 8;14:949-961. Epub 2020 Jun 8.

Medical Affairs, Pfizer Inc, Montreal, QC, Canada.

Objective: Qualitative research exploring patient preferences regarding the mode of treatment administration for psoriatic arthritis (PsA) is limited. We report patient preferences and their reasons across PsA treatment modes.

Methods: In this global, cross-sectional, qualitative study, interviews were conducted with adult patients with PsA in Brazil, France, Germany, Italy, Spain, the UK, and the US. Patients were currently taking a disease-modifying antirheumatic drug (DMARD). Patients indicated the order and strength of preference (0-100; 100 = strongest) across four modes of treatment administration: oral (once daily), self-injection (weekly), clinic injection (weekly), and infusion (monthly); reasons for preferences were qualitatively assessed. Descriptive statistics were reported. Fisher's exact tests and tests were conducted for treatment mode outcomes.

Results: Overall, 85 patients were interviewed (female, 60.0%; mean age, 49.8 years). First-choice ranking (%) and mean [standard deviation] preference points were: oral (49.4%; 43.9 [31.9]); self-injection (34.1%; 32.4 [24.8]); infusion (15.3%; 14.5 [20.0]); clinic injection (1.2%; 9.2 [10.0]). Of 48 (56.5%) patients with a strong first-choice preference (ie point allocation ≥60), 66.7% chose oral administration. Self-injection was most often selected as second choice (51.8%), clinic injection as third (49.4%), and infusion as fourth (47.1%). Oral administration was the first-choice preference in the US (88.0% vs 38.0% in Europe). The most commonly reported reason for oral administration as the first choice was speed and ease of administration (76.2%); for self-injection, this was convenience (75.9%). The most commonly reported reason for avoiding oral administration was concern about possible drug interactions (63.6%); for self-injection, this was a dislike of needles or the injection process (66.7%).

Conclusion: Patients with PsA preferred oral treatment administration, followed by self-injection; convenience factors were common reasons for these preferences. Overall, 43.5% of patients did not feel strongly about their first-choice preference and may benefit from discussions with healthcare professionals about PsA treatment administration options.
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http://dx.doi.org/10.2147/PPA.S242336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293411PMC
June 2020

Choosing a Mobile Sensor Technology for a Clinical Trial: Statistical Considerations, Developments and Learnings.

Ther Innov Regul Sci 2021 Jan 18;55(1):38-47. Epub 2020 Jun 18.

Strategic and Clinical Operations, Transparency Life Sciences, Inc., San Francisco, CA, USA.

The DIA Study Endpoints Community Working Group on Mobile Sensor Technology (MST) series addresses considerations that may be useful for selecting MST for use in a clinical trial. This article describes considerations regarding the selection of MST for clinical trials including expectations around technology specifications, verification (bench testing), regulatory clearance and certification status. We identify useful statistical methods needed to establish agreement of the MST with respect to a clinical 'gold' standard technology in terms of accuracy and precision, and to combine data across trials, data types or device versions. In addition to describing key considerations, this manuscript also serves as a central location citing those resources where additional detail can be found.
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http://dx.doi.org/10.1007/s43441-020-00188-2DOI Listing
January 2021

Crisaborole Ointment, 2%, for Treatment of Patients with Mild-to-Moderate Atopic Dermatitis: Systematic Literature Review and Network Meta-Analysis.

Dermatol Ther (Heidelb) 2020 Aug 20;10(4):681-694. Epub 2020 May 20.

Global Biometrics and Data Management (Statistics), Pfizer Inc., Groton, USA.

Introduction: There is a need to compare efficacy and safety profiles of crisaborole ointment, 2%, versus other topical treatments across randomized clinical trials (RCTs). We performed this review/network meta-analysis to evaluate the comparative efficacy and safety of crisaborole versus other topical pharmacologic therapies for mild-to-moderate atopic dermatitis (AD) among patients aged ≥ 2 years.

Methods: Searches were conducted in MEDLINE, Embase, the Cochrane Collection Central Register of Clinical Trials, and the Database of Abstracts of Reviews of Effects using Ovid to identify English language articles reporting RCTs of topical anti-inflammatory agents in patients aged ≥ 2 years with mild-to-moderate AD published between inception and 10 March 2020. This review used a prespecified protocol with eligibility criteria for population, interventions, comparisons, outcomes, and study design. Efficacy was evaluated using the Investigator's Static Global Assessment (ISGA) of clear (0) or almost clear (1) and expressed by hazard ratios (HR) with 95% credible intervals.

Results: Patients treated with crisaborole or tacrolimus ointment, 0.1% or 0.03%, versus vehicle alone were significantly more likely to achieve ISGA 0/1 at 28-42 days, with the greatest point estimate observed for the crisaborole comparison (hazard ratio: 2.07; 95% credible interval 1.76 to - 2.36; probability HR above 1 [p better]: 100.0%). Patients were also more likely to achieve ISGA 0/1 with crisaborole than with pimecrolimus cream, 1% (HR: 1.62; 95% credible interval 1.04-2.48; p better: 98.3%). While network meta-analysis for safety was not feasible because of data limitations, crisaborole pivotal studies (AD-301/AD-302) showed crisaborole was well tolerated.

Conclusions: Crisaborole was shown to be superior to vehicle and pimecrolimus and comparable to tacrolimus, 0.1% or 0.03%, with respect to ISGA 0/1 at 28-42 days in patients aged ≥ 2 years with mild-to-moderate AD. This evaluation of comparative efficacy of crisaborole further supports use of crisaborole as an effective therapeutic option in this population.
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http://dx.doi.org/10.1007/s13555-020-00389-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367970PMC
August 2020

The Inflammatory Bowel Disease Questionnaire in Randomized Controlled Trials of Treatment for Ulcerative Colitis: Systematic Review and Meta-Analysis.

J Patient Cent Res Rev 2020 27;7(2):189-205. Epub 2020 Apr 27.

Pfizer Inc., New York, NY.

Purpose: The 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32) is the most frequently used instrument to capture disease-specific quality of life in randomized clinical trials for ulcerative colitis. This review and meta-analysis provides the first synthesis of evidence regarding the sensitivity of IBDQ-32 total and domain scores to treatment efficacy.

Methods: A systematic literature search and risk-of-bias assessment yielded 14 articles that were included in the primary analysis. Treatments were categorized as efficacious if they met the primary efficacy endpoint (which was not the IBDQ-32); otherwise they were categorized as non-efficacious. A continuous measure of treatment efficacy was calculated for each primary efficacy endpoint. Meta-analysis using random-effects models compared standardized mean differences in IBDQ-32 total and domain change scores between target dose and control arms. Meta-regression compared the association between treatment efficacy and these outcomes.

Results: Studies with efficacious treatments showed larger mean improvements relative to controls in IBDQ-32 total scores and all 4 domains (Hedges' range: 0.49 to 0.67; P<0.001 for all). At the same time, patients in studies with non-efficacious treatments showed small and nonsignificant improvements in these outcomes relative to controls (Hedges' range: 0.05 to 0.23; P>0.09 for all). Meta-regression models showed that the magnitude of treatment efficacy was a positive predictor of these same IBDQ-32 outcomes.

Conclusions: These analyses found that IBDQ-32 scores are sensitive to treatment. The results provided here support the use of the IBDQ-32 to capture treatment benefits on quality of life for patients with ulcerative colitis.
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http://dx.doi.org/10.17294/2330-0698.1722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197888PMC
April 2020

Real-world treatment patterns in patients with advanced (stage III-IV) ovarian cancer in the USA and Europe.

Future Oncol 2020 May 24;16(15):1013-1030. Epub 2020 Apr 24.

Pfizer Inc, NY 10017, USA.

To analyze real-world data relating to treatment decision-making in stage III-IV ovarian cancer (OC). Real world data were collected from a survey of physicians and their patients (n = 2413) across Europe and the USA in 2017-2018. 49% had stage IVb disease. 39, 54 and 7% of patients received first-line (1L), second-line, or 7% third-line or later treatment. In the 1L (ongoing or completed), 93% received platinum-containing regimens, 26% bevacizumab-containing regimens and 1% a PARP inhibitor-containing regimen. In 1L maintenance treatment, 81% received bevacizumab, 17% platinum-containing treatments and 6% a PARP inhibitor. The most common 1L treatment for advanced ovarian cancer was platinum-containing chemotherapy. Of those receiving 1L maintenance therapy, 70-99% (across countries) received targeted therapy.
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http://dx.doi.org/10.2217/fon-2020-0083DOI Listing
May 2020

Costs and Health Outcomes Associated with Tofacitinib Treatment for Active Psoriatic Arthritis in the United States.

J Manag Care Spec Pharm 2020 Aug 20;26(8):1027-1038. Epub 2020 Apr 20.

Pfizer Inc, Collegeville, Pennsylvania.

Background: Psoriatic arthritis (PsA) is a chronic progressive inflammatory condition associated with significant direct and indirect costs. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Economic evaluations, alongside clinical data, help inform papers and formulary decisions in the United States.

Objective: To evaluate outcomes and costs of including tofacitinib in treatment strategies for PsA from a third-party U.S. payer perspective, using a health economic model.

Methods: A decision tree model was developed to evaluate treatment sequences (up to 4 lines of advanced PsA therapy) with or without tofacitinib. Patients included in the model had active PsA and a previous inadequate response (IR) to conventional synthetic disease-modifying antirheumatic drug (csDMARD) or tumor necrosis factor inhibitor (TNFi) therapy. The analysis time horizon was 2 years; decision points for continuing/switching treatments occurred quarterly, based on clinical response (assessed using the primary rheumatoid measure of efficacy, American College of Rheumatology [ACR]20 response only) and adverse drug reactions (ADRs). Costs included those related to ADRs and drug acquisition, monitoring, and administration. Other endpoints of PsA, such as assessment of enthesitis and dactylitis, were not integrated into the model.

Results: Treatment strategies including tofacitinib were associated with cost savings versus strategies without tofacitinib across all modeled scenarios, with an estimated 2-year cost saving of up to $8,454,858, based on 1 million insurants. Similarly, costs per member per month and per ACR20 responder were lower for sequences including tofacitinib versus sequences without. These savings arose because of lower ADR and drug acquisition/administration costs for sequences including tofacitinib. Deterministic sensitivity analyses showed these results to be robust.

Conclusions: This analysis suggests that including tofacitinib in the treatment of active PsA in csDMARD-IR or TNFi-IR patients is a cost-saving alternative to sequences without tofacitinib, potentially reducing costs for PsA advanced therapies by up to $8.4 million over 2 years for payers insuring 1 million individuals.

Disclosures: This work was sponsored by Pfizer Inc. Bungey is an employee of Decision Resources Group, which received financial support from Pfizer Inc to develop the treatment-cost model used in the development of this manuscript. Chang-Douglass was an employee of Decision Resources Group at the time of the analysis. During development of this publication, Chang-Douglass started a role at the National Institute for Health and Care Excellence (NICE). The publication only reflects her views and does not reflect the views of NICE. Hsu, Cappelleri, Young, and Woolcott are employees of Pfizer Inc and own stock or stock options in Pfizer Inc. The data reported in this manuscript have been previously presented at the American College of Rheumatology Annual Scientific Meeting; October 19-24, 2018; Chicago, IL, and the AMCP Annual Meeting and Expo; March 25-28, 2019; San Diego, CA.
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http://dx.doi.org/10.18553/jmcp.2020.19319DOI Listing
August 2020

Relationship between molecular response and quality of life with bosutinib or imatinib for chronic myeloid leukemia.

Ann Hematol 2020 Jun 19;99(6):1241-1249. Epub 2020 Apr 19.

Pfizer Inc, Groton, CT, USA.

Patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML) can be effectively treated with tyrosine kinase inhibitors (TKIs) and achieve a lifespan similar to the general population. The success of TKIs, however, requires long-term and sometimes lifelong treatment; thus, patient-assessed health-related quality of life (HRQoL) has become an increasingly important parameter for treatment selection. Bosutinib is a TKI approved for CP CML in newly diagnosed adults and in those resistant or intolerant to prior therapy. In the Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment (BFORE), bosutinib demonstrated a significantly higher major molecular response rate compared with imatinib, with maintenance of HRQoL (measured by the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire), after 12 months of first-line treatment. We examined relationships between molecular response (MR) and HRQoL. MR values were represented by a log-reduction scale (MRLR; a continuous variable). A repeated-measures longitudinal model was used to estimate the relationships between MRLR as a predictor and each FACT-Leu domain as an outcome. Effect sizes were calculated to determine strength of effects and allow comparisons across domains. The majority of FACT-Leu domains (with the exception of social well-being and physical well-being) demonstrated a significant relationship with MRLR (p < 0.05). Our results showed variable impact of clinical improvement on different dimensions of HRQoL. For patients who achieved MR, emotional well-being and leukemia-specific domains showed the greatest improvement, with medium differences in effect sizes, whereas social well-being and physical well-being had the weakest relationship with MR.
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http://dx.doi.org/10.1007/s00277-020-04018-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237399PMC
June 2020

A Large Cross-Sectional Survey Study of the Prevalence of Alopecia Areata in the United States.

Clin Cosmet Investig Dermatol 2020 1;13:259-266. Epub 2020 Apr 1.

Pfizer Inc., Cambridge, MA 02139, USA.

Purpose: Alopecia areata (AA) is an autoimmune disease characterized by the development of non-scarring alopecia. The prevalence is not well known, and estimates vary considerably with no recent estimates in the United States (US). The objective of this study was to define the current AA point prevalence estimate among the general population in the US overall and by severity.

Patients And Methods: We administered an online, cross-sectional survey to a representative sample of the US population. Participants self-screening as positive for AA using the Alopecia Assessment Tool (ALTO) also completed the Severity of Alopecia Tool (SALT) to measure the severity of disease as a percent of scalp hair loss. Self-reported AA participants were invited to upload photographs for adjudication of AA by 3 clinicians.

Results: The average age of participants was 43 years. Approximately half of the participants (49.2%) were male, and the majority were white (77.1%) and not of Hispanic origin (93.2%). Among the 511 self-reported AA participants, 104 (20.4%) uploaded photographs for clinician evaluation. Clinician-adjudicated point prevalence of AA was 0.21% (95% CI: 0.17%, 0.25%) overall, 0.12% (95% CI: 0.09%, 0.15%) for "mild" disease (≤50% SALT score), and 0.09% (95% CI: 0.06%, 0.11%) for "moderate to severe" disease (>50% SALT score) with 0.04% (95% CI: 0.02%, 0.06%) for the alopecia totalis/alopecia universalis (100% SALT score) "moderate to severe" subgroup. The average SALT score was 44.4% overall, 8.8% for "mild", and 93.4% for "moderate to severe".

Conclusion: This study suggests that the current AA prevalence in the US is similar to the upper estimates from the 1970s at approximately 0.21% (700,000 persons) with the current prevalence of "moderate to severe" disease at approximately 0.09% (300,000 persons). Given this prevalence and the substantial impact of AA on quality of life, the burden of AA within the US is considerable.
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http://dx.doi.org/10.2147/CCID.S245649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131990PMC
April 2020