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OBJECTIVE This study assessed associations between severity of, and prescription medication use for, chronic low back pain (CLBP) and health-related quality of life, health status, work productivity, and healthcare resource utilization. METHODS This cross-sectional study utilized SF-12, EQ-5D-5L, and work productivity and activity impairment (WPAI) questionnaires, and visits to healthcare providers among adults with self-reported CLBP participating in the National Health and Wellness Survey in Germany, France, UK, Italy, and Spain. Respondents were stratified into four groups according to pain severity (mild or moderate/severe) and prescription medication use (Rx-treated or Rx-untreated). Differences between groups were estimated using generalized linear models controlling for sociodemographics and health characteristics. RESULTS Of 2086 respondents with CLBP, 683 had mild pain (276 Rx-untreated, 407 Rx-treated) and 1403 had moderate/severe pain (781 Rx-untreated, 622 Rx-treated). Respondents with moderate/severe pain had significantly worse health-related quality of life (SF-12v2 physical component summary), health status (EQ-5D-5L), and both absenteeism and presenteeism compared with those with mild pain, including Rx-untreated (moderate/severe pain Rx-untreated vs. mild pain Rx-untreated, p ≤ 0.05) and Rx-treated (moderate/severe pain Rx-treated vs. mild pain Rx-treated, p ≤ 0.05) groups. Significantly more visits to healthcare providers in the last 6 months were reported for moderate/severe pain compared with mild pain for Rx-treated (least squares mean 13.01 vs. 10.93, p = 0.012) but not Rx-untreated (8.72 vs. 7.61, p = 0.072) groups. Health-related quality of life (SF-12v2 physical component summary) and health status (EQ-5D-5L), as well as absenteeism and presenteeism, were significantly worse, and healthcare utilization was significantly higher, in the moderate/severe pain Rx-treated group compared with all other groups (all p ≤ 0.05). CONCLUSION Greater severity of CLBP was associated with worse health-related quality of life, health status, and absenteeism and presenteeism, irrespective of prescription medication use. Greater severity of CLBP was associated with increased healthcare utilization in prescription medication users.

Introduction Atopic dermatitis (AD) severity was measured in two phase 3 US studies of crisaborole ointment, 2%, in patients aged ≥ 2 years using the Investigator’s Static Global Assessment (ISGA), an FDA-recommended scale. Eczema Area and Severity Index (EASI) is a validated scale used globally to assess AD severity in clinical trials. The objective of this study is to aid interpretability of ISGA by translating ISGA scores to EASI scores. Methods ISGA was mapped to EASI using published EASI severity strata by Chopra et al. and Leshem et al. and pooled data from phase 3 trials CrisADe CORE 1 and CORE 2, which evaluated crisaborole in patients aged ≥ 2 years with mild-to-moderate AD (crisaborole, n = 1016; vehicle, n = 506). Least squares mean (LSM) percentage change from baseline (%CFB) in EASI and proportion of patients with 50%, 75%, and 90% improvement (EASI-50, EASI-75, and EASI-90, respectively) on day 29 were computed for mapped EASI. The relationship between changes in ISGA and changes in EASI was assessed using data from three abrocitinib trials. Results ISGA was mapped to EASI using 70,000 random simulations. LSM (standard error) for %CFB in mapped EASI at day 29 (crisaborole versus vehicle) was −26.3% (17) versus 45.2% (35) (P = 0.0671) using Chopra strata and −43.1% (4.6) versus −5.2% (8.4) (P

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

Srinivas R Nalamachu,1 Rebecca L Robinson,2 Lars Viktrup,3 Joseph C Cappelleri,4 Andrew G Bushmakin,4 Leslie Tive,5 Jennifer Mellor,6 Niall Hatchell,6 James Jackson6 1Mid America PolyClinic, Overland Park, KS, USA; 2Patient Outcomes and Real-World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Bio-Medicines Core Team, Eli Lilly and Company, Indianapolis, IN, USA; 4Statistics, Pfizer Inc, Groton, CT, USA; 5Medical Affairs, Pfizer Inc, New York, NY, USA; 6Real World Research, Adelphi Real World, Bollington, Cheshire, UKCorrespondence: Rebecca L RobinsonEli Lilly and Company, Lilly Research Labs, Lilly Corporate Center, Indianapolis, IN 46285, USATel +1 317-224-5833Fax +1 317-277-0490Email rlrobinson@lilly.comPurpose: 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 (P< 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 P< 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.Keywords: nonprescription drugs, prescription drugs, therapeutics, pain management, practice patterns, physicians

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).

Background: Several pharmaceutical treatments for chronic pain caused by osteoarthritis (OA) and chronic low back pain (CLBP) are available or currently under development, each associated with different adverse events (AEs) and efficacy profiles. It is therefore important to understand what trade-offs patients are willing to make when choosing between treatments. Methods: A discrete-choice experiment (DCE) was conducted with 437 adults with chronic pain caused by OA and/or CLBP. Respondents were presented with a series of scenarios and asked to choose between pairs of hypothetical treatments, each defined by six attributes: level of symptom control; risks of heart attack, rapidly progressive osteoarthritis and dependency; frequency and mode of administration and cost. Attributes were based on known profiles of oral nonsteroidal anti-inflammatory drugs, opioids and injected nerve growth factor inhibitors, the last of which were under clinical development at the time of the study. Data were analysed using a latent class (LC) model to explore preference heterogeneity. Results: Overall, respondents considered improving symptom control and reducing risk of physical dependency to be the most important attributes. The LC analysis identified four participant classes: an ‘efficacy-focused’ class (33.7%), a ‘cost-averse’ class (29.4%), a ‘physical-dependence–averse’ class (19.6%) and a ‘needle-averse’ class (17.3%). Subgroup membership was incompletely predicted by participant age and their responses to comprehension questions. Conclusions: Preference heterogeneity across respondents indicates a need for a personalized approach to offering treatment options. Symptom improvement, cost, physical dependence and route of administration might be important to different patients. Significance: Multiple treatment options that differ substantially in terms of efficacy and adverse events are available for the management of chronic pain. With a growing emphasis on a patient-centred care model that incorporates patients’ priorities and values into treatment decisions, there is a need to understand how individuals with chronic musculoskeletal pain balance the benefits and risks of treatment and how treatment priorities vary among individuals. This study was designed to identify patient preferences for different characteristics of treatments for the management of chronic pain and to investigate how preferences differ among respondents.

Patients with psoriatic arthritis (PsA) experience impaired health-related quality of life (HRQoL). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA, which has been associated with improvements in dermatologic endpoints in patients with PsA. To assess the extent to which tofacitinib affects patient HRQoL via improvements in dermatologic symptoms, including itch, data were pooled from patients with PsA who received tofacitinib in phase III studies (NCT01866668 and NCT01882439). Mediation modeling assessed the indirect effects (via Itch Severity Item [ISI] and Physician’s Global Assessment of Psoriasis [PGA-PsO]) and direct effects (via all other factors) of tofacitinib treatment on dermatology-specific HRQoL (measured by Dermatology Life Quality Index [DLQI]). In the initial model, the treatment effect on DLQI was largely mediated by itch (ISI, p &lt, 0.0001) and PGA-PsO (p &lt, 0.01). The model was re-specified to assess the indirect effects only of itch and PGA-PsO on DLQI. Here, 17.7% of the treatment effect on DLQI was attributable to PGA-PsO (p = 0.0006), and 82.3% to itch (p &lt, 0.0001). Tofacitinib-dependent improvements in DLQI were primarily mediated by itch relief, in addition to improvements in PGA-PsO.

BackgroundPain is a core domain of psoriatic arthritis (PsA). This post hoc analysis evaluated time to pain improvement and the impact of baseline pain severity on pain response in patients with PsA receiving tofacitinib.MethodsData from two trials (NCT01877668; NCT01882439) in patients receiving tofacitinib 5 mg twice daily, placebo switching to tofacitinib 5 mg twice daily at month 3 (placebo-to-tofacitinib) or adalimumab (NCT01877668 only) were included. Improvement in pain (≥30%/≥50% decrease from baseline in Visual Analogue Scale pain score) was assessed; median time to initial (first post-baseline visit)/continued (first two consecutive post-baseline visits) pain improvement was estimated (Kaplan-Meier) for all treatment arms. A parametric model was used to determine the relationship between baseline pain severity and time to pain response in patients receiving tofacitinib.ResultsAt month 3, more patients experienced pain improvements with tofacitinib/adalimumab versus placebo. Median days (95% CI) to initial/continued pain improvements of ≥30% and ≥50%, respectively, were 55 (29–57)/60 (57–85) and 85 (57–92)/171 (90–not estimable (NE)) for tofacitinib, versus 106 (64–115)/126 (113–173) and 169 (120–189)/NE (247–NE) for placebo-to-tofacitinib. Pain improvements were also experienced more quickly for adalimumab versus placebo. Predicted time to ≥30%/≥50% pain improvement was shorter in patients with higher baseline pain versus lower baseline pain (tofacitinib arm only).ConclusionsIn patients with PsA, pain improvements were experienced by more patients, and more rapidly, with tofacitinib and adalimumab versus placebo. In those receiving tofacitinib, higher baseline pain was associated with faster pain improvements.

Background Several different Physician Global Assessment (PGA) versions have been used in clinical studies as a co-primary end point to evaluate psoriasis severity. Tofacitinib is an oral Janus kinase inhibitor. We performed an analysis of the PGA using data from studies of tofacitinib in moderate to severe chronic plaque psoriasis. Methods Data from 3641 patients with moderate to severe chronic plaque psoriasis, enrolled in one of four phase III tofacitinib studies (OPT Pivotal 1 and 2, OPT Compare and OPT Retreatment), were used to evaluate a three-item PGA scale. Results Confirmatory Factor Analyses showed that equal weighting of the three items (erythema, induration and scaling) was appropriate. The PGA demonstrated acceptable test–retest reliability (Intraclass Correlation Coefficient, 0.7) and internal consistency (Cronbach’s Coefficient Alpha ≥ 0.9 at primary time points). The Clinically Important Difference was estimated as 0.55 (95% confidence interval: 0.546–0.563). Known-group validity was shown by demonstrating that PGA scores could discriminate between different degrees of disease severity. The PGA was significantly correlated with other clinical end points in the studies (Psoriasis Area and Severity Index, r = 0.75–0.79; Dermatology Life Quality Index, r = 0.44–0.57; Patient Global Assessment, r = 0.66–0.72). Conclusions Consistent with previous findings from a phase II study, these results indicate that this PGA is a valid, reliable instrument for evaluating disease severity in clinical studies of psoriasis. Electronic supplementary material The online version of this article (10.1186/s12895-019-0088-2) contains supplementary material, which is available to authorized users.

Crisaborole ointment is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis. Using pooled data from two phase 3 studies (NCT02118766/NCT02118792), mediation modeling determined the interrelationship among pruritus, quality of life (QoL), and treatment. Patients aged ≥ 2 years received crisaborole ointment 2% or vehicle twice daily for 28 days. QoL measures were Dermatology Life Quality Index (DLQI) (≥ 16 years) and Children’s Dermatology Life Quality Index (CDLQI) (2–15 years). Pruritus was assessed by the Severity of Pruritus Scale (4-point scale from 0 to 3). The indirect effect of crisaborole on QoL mediated through its effect on pruritus was 51% (DLQI model, p 0.05). Mediation modeling shows that crisaborole affects QoL mostly indirectly through pruritus severity reduction.

Purpose To evaluate the relationship between self-reported concerns about becoming addicted to a medication and health-related quality of life (HRQoL) in patients with osteoarthritis (OA). Methods This real-world study used patient-level cross-sectional survey data collected from the US Adelphi Disease Specific Programme (DSP). The DSP for OA selected 153 physicians who collected de-identified data on their next nine adult patients with OA. Each patient completed a disease-relevant survey, which included the Likert-scale question, “I am concerned about becoming addicted to my medicine,” (CAA) with responses ranging from “completely disagree” [1] to “completely agree” [5]. HRQoL was measured by the EQ-5D-5L index value and the EQ Visual Analogue Scale (VAS). A set of ordinary least squares regressions using HRQoL measures as outcomes and CAA as a continuous predictor were estimated. Standardized effect size (ES) was used to gauge the magnitude of effects. Results A total of 866 patients with OA completed the survey (female, 61.2%; White, 77.7%; mean age, 64.2 years). Of the 775 patients who completed the CAA question, almost one-third responded that they “agree” (18%) or “completely agree” (11%), while 27% responded “completely disagree” and 20% “disagree.” Regression analyses found that patients who have concerns about medication addiction have significantly different EQ-5D-5L index values and EQ VAS scores compared with patients who do not have this concern (p Conclusion Our findings suggest that concern about medication addiction in patients with OA may have an impact on patient HRQoL, with more concerned patients reporting poorer HRQoL outcomes.

Background In psoriatic arthritis (PsA), further understanding of the relationships between clinical measures and patient-reported outcomes (PROs) is needed. This post hoc analysis evaluated associations between minimal disease activity (MDA) as a continuous outcome (termed ScoreMDA) or Psoriatic Arthritis Disease Activity Score (PASDAS) with selected PROs not included in the composite measures. Methods Data from two phase 3 studies of tofacitinib in PsA (OPAL Broaden [NCT01877668; N = 422]; OPAL Beyond [NCT01882439; N = 394]) were included. MDA (binary outcome) was defined as meeting ≥5/7 criteria. For ScoreMDA, each criterion was assigned a value (1 = true; 0 = false; score range, 0–7; scores ≥5 indicated MDA). For PASDAS (score range, 0–10), higher scores indicated worse disease activity. PROs analyzed included Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Patient’s Assessment of Arthritis Pain visual analog scale (Pain VAS), and EuroQoL-Five Dimensions-Three Level Health Questionnaire visual analog scale (EQ-5D-3L VAS) and utility index. Relationships were evaluated using repeated measures regression models. Results Similar, approximately linear relationships were confirmed between PASDAS or ScoreMDA and PROs in both studies. In OPAL Broaden and OPAL Beyond, a one-point difference in PASDAS was associated with clinically relevant differences in PROs, including EQ-5D-3L VAS (− 6.7 mm, − 6.9 mm), Pain VAS (9.9 mm, 10.7 mm), and FACIT-F (− 2.8, − 3.3). A one-point difference in ScoreMDA was associated with clinically relevant differences in PROs, including EQ-5D-3L VAS (5.0 mm, 5.5 mm) and FACIT-F (1.9, 2.7) in OPAL Broaden and OPAL Beyond, respectively. Conclusions Linear associations between PASDAS or ScoreMDA and PROs provide interpretable and quantifiable metrics between composite clinical measures and PROs, highlighting the importance of these measures in understanding the relevance of treat-to-target goals in PsA. Trial registration ClinicalTrials.gov, NCT01877668. Registered on June 12, 2013. ClinicalTrials.gov, NCT01882439. Registered on June 18, 2013

Introduction The Investigator’s Static Global Assessment (ISGA) is a 5-point rating scale that is recommended by the US Food and Drug Administration for assessing the severity of atopic dermatitis (AD), and ISGA success is a widely used endpoint in AD clinical studies. In this study, we seek to interpret the relationship of ISGA with treatment, pruritus, and quality of life (QoL) by conducting post hoc analyses of pooled data from two phase 3 crisaborole studies. Methods Patients aged ≥ 2 years with baseline ISGA of 2 (mild) or 3 (moderate) were randomly assigned 2:1 to receive crisaborole or vehicle for 28 days. Disease severity, pruritus severity, and QoL were assessed with the ISGA, Severity of Pruritus Scale (SPS), and Dermatology Life Quality Index (DLQI; patients aged ≥ 16 years), or Children’s Dermatology Life Quality Index (CDLQI; patients aged 2–15 years), respectively. The effect of treatment on ISGA and the relationship between ISGA and QoL were analyzed using a longitudinal repeated-measures model. The interrelationship between treatment, disease severity, pruritus, and QoL was analyzed with a mediation model. Results Overall, 1522 patients (crisaborole, n = 1016; vehicle, n = 506) were included. Estimated longitudinal profiles indicated changes in ISGA by day 8 were large for crisaborole (effect size [ES]: − 0.68) and small for vehicle (ES: − 0.34). There was a direct relationship between ISGA and DLQI and CDLQI severity bands in the longitudinal repeated-measures model. For both QoL mediation models, treatment effects on QoL were mediated indirectly by reduction in pruritus (DLQI, 42.4%; CDLQI, 58.1%) and disease severity (DLQI, 12.2%; CDLQI, 33.1%). Conclusions These post hoc analyses suggest that ISGA success is a clinically meaningful endpoint associated with reduction in the severity of pruritus and improvement in QoL. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00506-y.

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. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-020-00474-9.

Summary Objective To quantify preferences for attributes of potential analgesic treatments for moderate-to-severe pain associated with osteoarthritis (OA) and/or chronic low back pain (CLBP) as relevant to injectable nerve growth factor (NGF)–inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids. Methods We used a discrete-choice experiment (DCE) to elicit preferences for attributes of OA and CLBP pharmaceutical treatments, and a best-worst scaling (BWS) exercise to further characterize the relative importance of treatment-related side-effect risks. The survey was completed online by 602 US residents with self-reported chronic, moderate-to-severe OA pain and/or CLBP who had tried, had contraindications for, or were unwilling to take currently available pharmaceutical therapies. In the DCE, respondents repeatedly chose between two hypothetical treatments defined by six attributes (symptom control; treatment-related risks of (1) severe joint problems, (2) heart attack, and (3) physical dependence; mode/frequency of administration; and cost). In the BWS exercise, respondents evaluated ten side-effect risks. Random-parameters logit models were estimated; conditional relative attribute importance, maximum acceptable risks, and willingness to pay were calculated. Results The most important DCE attributes were improving symptom control (scaled conditional relative importance, 10.00) and reducing risk of physical dependence (6.99). The three most important BWS attributes were, in rank order, risks of stroke, physical dependence, and heart attack. Respondents were willing to accept a > 4% treatment-related risk of severe joint problems for even modest symptom improvement. Conclusion A pharmaceutical treatment with a risk of severe joint problems was viewed as an acceptable alternative to other treatments with comparable efficacy but risks associated with NSAIDs or opioids.

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’ g 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’ g 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.

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.

Postmenopausal women (PMW) can experience side-effects (breast pain/tenderness and vaginal spotting/bleeding) associated with estrogen plus progestin therapies (EPTs). To assess these outcomes, the Breast Pain and Tenderness Daily Diary (BPT-DD) and the Vaginal Bleeding and Spotting Daily Diary (VBS-DD) were developed for electronic completion (eDiaries). This study evaluated the psychometric properties of the eDiaries.The eDiaries were completed daily for 28 days by 202 PMW experiencing breast pain/tenderness and/or vaginal spotting/bleeding while on EPTs. Confirmatory factor analysis (CFA) investigated the BPT-DD structure. Response distributions, test-retest reliability (intraclass correlation coefficient [ICC]), internal consistency (BPT-DD only), and construct validity (via known groups and convergent validity analyses) were assessed.Completion rates were high: over 90% of women missed3 daily entries. CFA supported the BPT-DD unidimensional structure (Bentler's Comparative Fit Index0.98). BPT-DD inter-item correlations (r = 0.77-0.89) and internal consistency (Cronbach's alpha = 0.95-0.97) were high and good test-retest reliability was demonstrated (ICC ≥ 0.70). The eDiaries correlated moderately (0.40), in a logical pattern with other instruments, supporting convergent validity. Known-groups analyses indicated both measures demonstrated significant differences between patients of differing severity (p 0.001).The study provides evidence of strong psychometric properties for the BPT-DD and VBS-DD to assess breast pain/tenderness and spotting/bleeding in PMW.

Background and aims This review is the first to evaluate the burden of ulcerative colitis [UC] on patients' quality of life by synthesizing data from studies comparing scores from the SF-36® Health Survey, a generic measure assessing eight quality-of-life domains, between UC patients and matched reference samples. Methods A systematic review of the published literature identified articles reporting SF-36 domains or physical and mental component summary scores [PCS, MCS] from UC and reference samples. Burden of disease for each SF-36 domain was then summarized across studies by comparing weighted mean differences in scores between patient and reference samples with minimally important difference thresholds. Results Thirty articles met pre-specified inclusion criteria. SF-36 scores were extracted from five samples of patients with active disease, 11 samples with a mixture of disease activity, five samples of patients in clinical remission, and 13 samples of patients following proctocolectomy with ileostomy or ileal pouch-anal anastomosis, along with respective reference samples. Clinically meaningful burden was observed in samples with active or mixed disease activity [deficits: PCS = 5.6, MCS = 5.5] on all SF-36 domains except Physical Functioning. No burden was observed in samples in remission or post-surgical patients [deficits: PCS = 0.8, MCS = 0.4] except for the General Health perception domain. Conclusions Patients with active UC experience a clinically meaningful burden of disease across most aspects of quality of life. Patients with inactive UC exhibit negligible disease burden and are comparable to the general population on most quality-of-life outcomes. Thus, treatments which effectively induce and maintain remission may restore physical and mental health status.

Background:Due to its impact on their health-related quality of life (QoL), fatigue is considered a core domain of disease assessment in patients (pts) with ankylosing spondylitis (AS). Psychometric data analyses in pts with rheumatoid and psoriatic arthritis have previously demonstrated that the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) is a reliable and valid measure in these pt populations,1,2 but there are limited data supporting the psychometric validity and reliability of the FACIT-F scale in adult pts with active AS.Objectives:To further evaluate the psychometric properties of the FACIT-F scale in adult pts with active AS.Methods:This post hoc analysis used data from the Phase (P)2 (NCT01786668, Study 1) and P3 (NCT03502616, Study 2) studies of tofacitinib in pts with active AS. Second-order confirmatory analysis (CFA) evaluated the measurement model of FACIT-F with two domains (Experience and Impact) and the total score at baseline (BL) and the studies’ respective primary analysis time points, Week (W)12 (Study 1) or W16 (Study 2). At the same time points, internal consistency reliability was examined by Cronbach’s Coefficient alpha (α), and convergent validity was assessed through correlations of FACIT-F domain and total scores with a set of pt-reported outcomes (PROs): Pt Global Assessment of Disease Activity (PtGA), total back pain/nocturnal spinal pain due to AS, Short Form-36 Health Survey (SF-36v2), Bath AS Functional Index, Bath AS Disease Activity Index and ASQoL. Test-retest reliability was assessed by calculating Intraclass Correlation Coefficients (ICCs). The known-groups validity assessment was derived from an anchor-based repeated measures longitudinal model, with PtGA scores as the anchor (PtGA represented pt state from ‘no disease activity’ to ‘very active disease’ [PtGA=0 and 10, respectively]), and FACIT-F domain/total scores as the outcome. Estimations of ability to detect change and meaningful within-pt change (MWPC) were derived from anchor-based repeated measures longitudinal models, with change from BL in PtGA scores as the anchor and change from BL in FACIT-F domain/total scores as the outcome.Results:The CFA model fit the data well (Bentler’s Comparative Index ≥0.92 at BL, W12 [Study 1] and W16 [Study 2]), supporting the measurement model of the FACIT-F scale in pts with AS. Across time points in each study, the FACIT-F domain and total scores demonstrated excellent internal consistency (Cronbach’s Coefficient α ≥0.88), and correlations between FACIT-F domain/total scores, and all PROs assessed generally exceeded 0.40. Generally, in both studies, the largest correlations (0.62–0.85) were between FACIT-F domain/total scores and the SF-36v2 vitality domain score and ASQoL. Test-retest reliability was acceptable for all FACIT-F domain/total scores (ICC ranged from 0.75–0.89 in both studies). An approximately linear relationship was observed between FACIT-F total scores and PtGA scores in both studies (Figure), as well as for Experience and Impact domain scores. The differences in FACIT-F domain/total scores were large and statistically significant between ‘no disease activity’ and ‘very active disease’ pt groups (standardised effect size ≥1.17), supporting known-groups validity. Ability to detect change was evidenced by an approximately linear relationship between changes in PtGA and FACIT-F domain/total scores in both studies; when pts experienced a change in PtGA, values for FACIT-F domain/total scores changed accordingly. Conservatively, MWPC was estimated as 6.3 for FACIT-F total score, and 2.8 and 3.6 for FACIT-F Experience and Impact domain scores, respectively.Conclusion:This quantitative analysis of data from two clinical studies of tofacitinib demonstrates the validity and reliability of the FACIT-F scale in adult pts with active AS. Therefore, these findings support the use of FACIT-F in AS studies.References:[1]Cella et al. J Rheumatol 2005; 32: 811-819.[2]Cella et al. J Patient Rep Outcomes 2019; 3: 30.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Kirsten Woollcott, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:David Cella Consultant of: AbbVie, Alexion Pharmaceuticals, Astellas Pharma, Bayer, Bristol-Myers Squibb, Clovis Oncology, Evidera, Exelixis, Horizon Therapeutics, Janssen, Merck/Schering-Plough, National Academy of Sciences, Novartis Pharma K.K. (Japan), Pfizer Inc, PledPharma and Regeneron, William Lenderking Shareholder of: Pfizer Inc, Employee of: Evidera, Peter Chongpinitchai Employee of: Evidera, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Oluwaseyi Dina Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Victoria Navarro-Compán Speakers bureau: AbbVie, Janssen, Eli Lilly, MSD, Pfizer Inc, UCB, Consultant of: AbbVie, Janssen, Eli Lilly, MSD, Pfizer Inc, UCB, Grant/research support from: AbbVie, Novartis

Tofacitinib is an oral Janus kinase inhibitor. This post-hoc analysis aimed to investigate the psychometric properties of the Itch Severity Item (ISI), a numeric rating scale from 0 (no itching) to 10 (worst possible itching) for pruritus in psoriasis, and review the effect of tofacitinib on pruritus in patients with psoriasis participating in Phase 3 studies (N = 3,641). The ISI showed high test-retest reliability (intra-class correlation coefficient: 0.84). The clinically important difference was defined as a 1.48-point change, using Patient Global Assessment as an anchor. Mean changes from baseline in ISI scores with tofacitinib were significantly greater than placebo by Day 2 and exceeded the clinically important difference by Week 4 and Week 2 for tofacitinib 5 and 10 mg twice daily, respectively. The sound psychometric properties of the ISI as an assessment tool for pruritus in psoriasis were confirmed. Tofacitinib provided clinically meaningful improvements in psoriatic pruritus versus placebo.

To conduct a systematic literature review of the reliability, construct validity, and responsiveness of the SF-36® Health Survey (SF-36) in patients with ulcerative colitis (UC). We performed a systematic search of electronic medical databases to identify published peer-reviewed studies which reported scores from the eight scales and/or two summary measures of the SF-36 collected from adult patients with UC. Study findings relevant to reliability, construct validity, and responsiveness were reviewed. Data were extracted and summarized from 43 articles meeting inclusion criteria. Convergent validity was supported by findings that 83% (197/236) of correlations between SF-36 scales and measures of disease symptoms, disease activity, and functioning exceeded the prespecified threshold (r ≥ |0.40|). Known-groups validity was supported by findings of clinically meaningful differences in SF-36 scores between subgroups of patients when classified by disease activity (i.e., active versus inactive), symptom status, and comorbidity status. Responsiveness was supported by findings of clinically meaningful changes in SF-36 scores following treatment in non-comparative trials, and by meaningfully larger improvements in SF-36 scores in treatment arms relative to controls in randomized controlled trials. The sole study of SF-36 reliability found evidence supporting internal consistency (Cronbach’s α ≥ 0.70) for all SF-36 scales and test–retest reliability (intraclass correlation coefficient ≥0.70) for six of eight scales. Evidence from this systematic literature review indicates that the SF-36 is reliable, valid, and responsive when used with UC patients, supporting the inclusion of the SF-36 as an endpoint in clinical trials for this patient population.

Objective Conjugated estrogens/bazedoxifene (CE/BZA) has demonstrated benefit in vulvar-vaginal atrophy (VVA, part of genitourinary syndrome of menopause) and the sexual function domain of the Menopause-specific Quality of Life (MENQOL) questionnaire. The study’s objective was to determine the relationship of VVA symptoms and clinical parameters with MENQOL sexual functioning in postmenopausal women receiving VVA treatment. Study design Post hoc analysis data were derived from the 12-week SMART-3 trial, which evaluated CE/BZA’s effect on VVA in nonhysterectomized postmenopausal women (aged 40–65 years) experiencing one or more moderate to severe VVA symptoms (dryness, itching/irritation, pain with intercourse) and vaginal pH > 5.0 (N = 664). Main outcome measures Repeated measures models were used to determine relationships of VVA symptoms and clinical parameters (vaginal pH, parabasal/superficial cells) with sexual functioning; sensitivity analyses were performed to check assumptions of linearity. Results VVA symptoms showed an approximately linear relationship with sexual functioning. A 1-point improvement in pain on intercourse (which has a large effect size [ES] = 0.85) corresponded to medium improvement (ES = 0.57) in MENQOL sexual functioning. Equivalent improvements (in terms of ES) in dryness and itching/irritation corresponded to small to medium (ES = 0.35) and small (ES = 0.27) improvements in sexual functioning, respectively. The same ES improvement in clinical parameters corresponded to small-trivial improvements in sexual functioning. Conclusions VVA symptoms have an approximately linear relationship with sexual functioning. Sexual functioning was most improved when pain on intercourse was reduced. Similar magnitudes of improvements in other VVA symptoms were linked with smaller, though potentially beneficial, improvements in sexual functioning. Changes in clinical parameters had only small or trivial associations with sexual functioning. Trial registration number NCT00238732

The 33-item Overactive Bladder questionnaire (OAB-q; 1-week recall version) has been psychometrically validated in middle-aged, generally healthy patients with overactive bladder. The present analysis was conducted to determine the psychometric validity of the OAB-q in medically complex elderly patients.OAB-q structure was evaluated using a second-order confirmatory factor analysis (CFA) model with five domains and one aggregated domain, using pooled data from two clinical trials (786 observations) for urgency urinary incontinence (UUI). Psychometric validity was evaluated with CFA, Cronbach coefficient α (CCA) for reliability, Spearman correlations for convergent validity, differences in OAB-q scores in relation to UUI severity and Patient Perception of Bladder Condition (PPBC) scores for known-groups validity, and effect size (ES) of differences in mean scores of OAB-q domains over time for treatment responsiveness.Participants were predominantly female (82.2%) and white (85.9%); mean age was 75.0 years. The second-order CFA was confirmed with a Bentler's comparative fit index of 0.90, t values for path coefficients of1.96, and standardized path coefficients of0.40. OAB-q domains demonstrated good internal consistency (CCA0.7). Convergent validity was supported by moderate correlations (0.4-0.7) between OAB-q domain and PPBC scores. Significant differences in OAB-q domain scores between groups with different symptom severity established known-groups validity. Significant changes in mean OAB-q scores from baseline to week 12 with moderate-to-large ES (0.50-0.80) demonstrated treatment responsiveness.The OAB-q demonstrates reliability, concurrent and discriminant validity, and responsiveness to treatment. The evidence shows that the OAB-q is psychometrically sound for use in medically complex elderly patients with overactive bladder.

Background:Treatment effect on pain is a priority for patients (pts) with psoriatic arthritis (PsA) and physicians. As pain is multidimensional, there is growing interest to understand the mechanisms of pain relief during treatment. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Previous analyses showed that the effect of tofacitinib on pain in pts with PsA was partially mediated through improvement of inflammation as assessed by C-reactive protein (CRP) and Swollen Joint Count (SJC). Additional potential inflammation-associated mediators that might contribute to tofacitinib’s effect on pain include enthesitis and skin disease.Objectives:To describe the interrelationship between pain, tofacitinib treatment and potential inflammatory-associated outcomes, using mediation modelling.Methods:Data from two Phase 3 studies (OPAL Broaden [NCT01877668]; OPAL Beyond [NCT01882439]) of pts with active PsA treated with tofacitinib 5 mg twice daily (BID) or placebo were used; pts were tumour necrosis factor inhibitor (TNFi)-naïve or had previous inadequate response to ≥1 TNFi. All pts were treated continuously with a single conventional synthetic DMARD. Analyses were completed using pooled and individual study data at Months 1 and 3 (using mean scores across visits). Mediation modelling seeks to explain mechanisms underlying observed relationships between independent and dependent variables via other variables (mediators). This initial model included: treatment as the independent (explanatory) binary variable (tofacitinib 5 mg BID vs placebo); pain, measured by Patient’s Assessment of Arthritis Pain (VAS, 0–100 mm), as the dependent (outcome) variable; mediators were: pt-reported Itch Severity Index (ISI); CRP; SJC; Psoriasis Area and Severity Index (PASI); and enthesitis, measured by Leeds Enthesitis Index (LEI) or Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). The final model was revised based on results of the initial model.Results:The initial model (N=329; pooled data) showed that tofacitinib treatment affects pain mainly indirectly via ISI, CRP, SJC, PASI and enthesitis (LEI), with 16.0% (p=0.53) attributable to the direct effect. The indirect effect via SJC (Conclusion:The majority of tofacitinib treatment effect on pain in pts with PsA is collectively mediated by itch, enthesitis and CRP, with itch being the main mediator of treatment effect (~37%), using mediation modelling analyses.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Kurt de Vlam Grant/research support from: Celgene, Eli Lilly, Pfizer Inc, Consultant of: AbbVie, Eli Lilly, Galapagos, Johnson & Johnson, Novartis, Pfizer Inc, UCB, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph F. Merola Consultant of: Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB Pharma, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and LEO Pharma, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ming-Ann Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

Annals of hematology 99(6), 1241-1249 (2020). doi:10.1007/s00277-020-04018-1, Published by Springer, Berlin ; Heidelberg ; New York

Background Pain is a core domain of psoriatic arthritis (PsA).1 Rapid, sustained pain reduction is a priority for patients (pts) and physicians when choosing treatment. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Objectives This post hoc analysis aimed to estimate time to clinically meaningful pain improvement with tofacitinib. Methods Data were analysed from 2 Phase 3 studies of tofacitinib in pts with active PsA and an inadequate response to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD) (OPAL Broaden; NCT01877668; 12-month study), or to ≥1 tumour necrosis factor inhibitor (OPAL Beyond; NCT01882439; 6-month study). Pts treated with tofacitinib 5 mg twice daily (BID) and placebo (PBO) advanced to tofacitinib 5 mg BID at Month 3 (PBO-tofacitinib), in combination with csDMARDs, were included in this analysis. Current arthritis pain severity was reported by pts using a 100 mm visual analogue scale, where higher scores indicated greater severity of pain. Pain improvement was defined as the first post-baseline improvement of ≥30% (meaningful change), ≥50% (substantial change) or ≥70% relative to baseline.2 Time-to-event analyses were performed using a Kaplan-Meier (KM) method on pooled data. Descriptive analyses of the rate of improvements by study were performed. Results Overall, 354 pts were available for analysis. Rates of pain improvement over time with tofacitinib 5 mg BID were approximately the same in both studies (Figure). By Month 1, ≥40% of pts experienced ≥30% pain improvement, and by Month 2, approximately 55% of pts experienced ≥30% pain improvement (Figure). KM analyses showed that pts receiving tofacitinib 5 mg BID achieved improvements in pain severity of 30–70% significantly faster compared with pts in the PBO-tofacitinib group (Table). The median time to ≥30% pain improvement was 55 days in the tofacitinib 5 mg BID group and 106 days in the PBO-tofacitinib group (pts switched to tofacitinib 5 mg BID at Month 3; p=0.0132). Similar trends between treatment groups were observed across other pain improvement thresholds. Conclusion In pts with active PsA, faster, clinically meaningful pain improvements were reported in pts receiving tofacitinib 5 mg BID vs pts receiving PBO who switched to tofacitinib 5 mg BID at Month 3. After switch from PBO to active treatment, pain improvement was observed in line with pts receiving active treatment from Day 0. To achieve pain improvement at greater thresholds, longer duration of active treatment was required. References [1] Orbai aM, et al. Ann Rheum Dis2017;76:673-80. [2] Dworkin RH, et al. J Pain2008;9:105-21. Acknowledgement This study was sponsored by Pfizer inc. Medical writing support was provided by Karleen Nicholson, PhD, on behalf of CMC Connect, a division of McCann Health Medical Communications Ltd, Macclesfield, UK, and was funded by Pfizer inc. Disclosure of interests Alexis Ogdie Grant/research support from: (To my university) Novartis, Pfizer, Grant/research support from: Novartis, Pfizer, Grant/research support from: Novartis, Pfizer, Grant/research support from: Novartis, Pfizer, Consultant for: abbVie, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly and Company, Novartis, Pfizer, and Takeda, Consultant for: abbVie, amgen, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly, Novartis, Pfizer inc, Takeda, Consultant for: abbvie, amgen, BMS, Celgene, Corrona, Lilly, Novartis, Pfizer, Takeda, Consultant for: abbvie, amgen, BMS, Celgene, Corrona, Lilly, Novartis, Pfizer, Takeda, Kurt de Vlam Consultant for: Pfizer inc, Consultant for: Johnson & Johnson, andrew G Bushmakin Shareholder of: Pfizer inc, Employee of: Pfizer inc, Joseph C Cappelleri Shareholder of: Pfizer inc, Employee of: Pfizer inc, Philip J Mease Grant/research support from: abbVie, amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Consultant for: abbVie, amgen, BMS, Galapagos, Gilead Sciences, inc., Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Speakers bureau: abbVie, amgen, BMS, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer and UCB, Roy Fleischmann Grant/research support from: abbVie, amgen, astraZeneca, Bristol-Myers Squibb, Celtrion, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer inc, Sanofi-Aventis, UCB, Consultant for: abbVie, amgen, astraZeneca, Bristol-Myers Squibb, Celtrion, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer inc, Sanofi-Aventis, UCB, Peter C. Taylor Grant/research support from: Celgene, Galapagos, Eli Lilly, UCB, Consultant for: abbVie, Galapagos, Gilead, Eli Lilly, Pfizer inc, Valderilio F azevedo Grant/research support from: abbVie, GSK, Janssen, Merck Serono, Novartis, Pfizer inc, UCB, Consultant for: abbVie, GSK, Janssen, Merck Serono, Novartis, Pfizer inc, UCB, Lara Fallon Shareholder of: Pfizer inc, Employee of: Pfizer inc, anna Maniccia Shareholder of: Pfizer inc, Employee of: Pfizer inc, John Woolcott Shareholder of: Pfizer inc, Employee of: Pfizer inc

Background Pain is a priority for patients (pts) with psoriatic arthritis (PsA) and physicians. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. As pain is a multidimensional phenomenon, there is growing interest in understanding mechanisms of pain relief during treatment. Objectives To examine the potential role of inflammation in the effect of tofacitinib on pain in pts with PsA, using mediation modelling. Methods Data were from the Phase 3 OPAL Broaden (NCT01877668) and OPAL Beyond (NCT01882439) studies of pts with active PsA treated with tofacitinib 5 mg twice daily (BID) or placebo; pts were tumour necrosis factor inhibitor (TNFi)-naive or had previous inadequate response (IR) to ≥1 TNFi. All pts continued on a stable dose of a single conventional synthetic DMARD. Analyses used pooled and individual trial data (mean scores from Months 1, 2 and 3). Mediation modelling seeks to explain mechanisms underlying an observed relationship between independent and dependent variables via other explanatory variables (mediators). In this model, pain (100 mm visual analogue scale) was the designated dependent variable, treatment (tofacitinib 5 mg BID vs placebo) the independent variable and inflammation, measured by swollen joint count (SJC) and C-reactive protein (CRP), was a mediator. The primary model designated treatment effect on pain mediated via CRP/SJC as an indirect effect and treatment effect not attributable to CRP/SJC as a direct effect. Models were re-specified based on initial results; model invariance by population (TNFi-naive vs TNFi-IR pts) was assessed. Results In the pooled analysis (N=469), 25.9% (p 0.05), respectively. The treatment effect on pain not attributable to CRP/SJC (direct effect) was 74.1% (p Conclusion While inflammation, as assessed by CRP/SJC, was a significant mediator of the overall treatment effect on pain in tofacitinib-treated pts with PsA, the majority of the treatment effect was not attributable to CRP/SJC changes. When mediators were assessed individually, only CRP was a significant mediator in the pooled analysis. In the re-specified model, CRP-mediated effects differed in TNFi-naive vs TNFi-IR pts, but this was not statistically significant. These results suggest that CRP/SJC-associated inflammation only partially explains pain in PsA; other potential mediators need to be identified to better understand the treatment effect of tofacitinib on pain. Acknowledgement Study sponsored by Pfizer Inc. Medical writing support provided by AG McCluskey, PhD, of CMC Connect; funded by Pfizer Inc. Disclosure of Interests Peter C. Taylor Grant/research support from: Celgene, Galapagos, Eli Lilly, UCB, Consultant for: AbbVie, Galapagos, Gilead, Eli Lilly, Pfizer Inc, Philip J Mease Grant/research support from: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Consultant for: AbbVie, Amgen, BMS, Galapagos, Gilead Sciences, Inc., Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer and UCB, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Roy Fleischmann Grant/research support from: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celtrion, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer Inc, Sanofi-Aventis, UCB, Consultant for: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celtrion, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer Inc, Sanofi-Aventis, UCB, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, John Woolcott Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Alexis Ogdie Grant/research support from: (To my university) Novartis, Pfizer, Grant/research support from: Novartis, Pfizer, Grant/research support from: Novartis, Pfizer, Grant/research support from: Novartis, Pfizer, Consultant for: AbbVie, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly and Company, Novartis, Pfizer, and Takeda, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly, Novartis, Pfizer Inc, Takeda, Consultant for: Abbvie, Amgen, BMS, Celgene, Corrona, Lilly, Novartis, Pfizer, Takeda, Consultant for: Abbvie, Amgen, BMS, Celgene, Corrona, Lilly, Novartis, Pfizer, Takeda, Valderilio F Azevedo Grant/research support from: AbbVie, GSK, Janssen, Merck Serono, Novartis, Pfizer Inc, UCB, Consultant for: AbbVie, GSK, Janssen, Merck Serono, Novartis, Pfizer Inc, UCB, Kurt de Vlam Consultant for: Pfizer Inc, Consultant for: Johnson & Johnson

Background To evaluate the measurement properties (e.g., content validity, reliability, and ability to detect change) of the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale in patients with active psoriatic arthritis (PsA). Methods One-on-one semi-structured qualitative interviews with adult patients with active PsA evaluated the content validity of FACIT-Fatigue. Quantitative measurement properties were evaluated using data from phase III tofacitinib randomized controlled trials (RCTs) in PsA: OPAL Broaden (NCT01877668) and OPAL Beyond (NCT01882439). Results Of 12 patients included in the qualitative study, 2 (17%) had mild, 8 (67%) had moderate, and 2 (17%) had severe PsA disease activity; 7 (58%) attributed fatigue to PsA, and 7 (58%) rated fatigue as important or extremely important. Most patients considered the FACIT-Fatigue items relevant to their PsA experience, and understood item content and response options as intended. In the psychometric analysis of RCT data, a second-order confirmatory factor model fit the data well (Bentler’s Comparative Fit Index ≥0.92). FACIT-Fatigue demonstrated good internal consistency (Cronbach’s coefficient α ≥ 0.90), test-retest reliability (Intraclass Correlation Coefficient ≥ 0.80) and a strong correlation with SF-36 Vitality (r > 0.80). A robust relationship between disease activity (based on Patient’s Global Assessment of Psoriasis and Arthritis) and FACIT-Fatigue was observed (effect sizes > 1.4), with clinically important difference for the FACIT-Fatigue total score estimated as 3.1 points, and the responder definition estimated as a 4-point improvement for FACIT-Fatigue total score. Conclusion Fatigue was confirmed to be an important symptom to patients with PsA, and FACIT-Fatigue was found to be a reliable and valid measure in this population. Electronic supplementary material The online version of this article (10.1186/s41687-019-0115-4) contains supplementary material, which is available to authorized users.

This study characterizes and quantifies the relationship of vasomotor symptoms (VMS) of menopause with menopause-specific quality of life (MSQOL) and sleep parameters to help predict treatment outcomes and inform treatment decision-making.Data were derived from a 12-week randomized, double-blind, placebo-controlled phase 3 trial that evaluated effects of two doses of conjugated estrogens/bazedoxifene on VMS in nonhysterectomized postmenopausal women (N = 318, mean age = 53.39) experiencing at least seven moderate to severe hot flushes (HFs) per day or at least 50 per week. Repeated measures models were used to determine relationships between HF frequency and severity and outcomes on the Menopause-Specific Quality of Life questionnaire and the Medical Outcomes Study sleep scale. Sensitivity analyses were performed to check assumptions of linearity between VMS and outcomes.Frequency and severity of HFs showed approximately linear relationships with MSQOL and sleep parameters. Sensitivity analyses supported assumptions of linearity. The largest changes associated with a reduction of five HFs and a 0.5-point decrease in severity occurred in the Menopause-Specific Quality of Life vasomotor functioning domain (0.78 for number of HFs and 0.98 for severity) and the Medical Outcomes Study sleep disturbance (7.38 and 4.86) and sleep adequacy (-5.60 and -4.66) domains and the two overall sleep problems indices (SPI: 5.17 and 3.63; SPII: 5.82 and 3.83).Frequency and severity of HFs have an approximately linear relationship with MSQOL and sleep parameters-that is, improvements in HFs are associated with improvements in MSQOL and sleep. Such relationships may enable clinicians to predict changes in sleep and MSQOL expected from various VMS treatments.

Objective Conjugated estrogens/bazedoxifene (CE/BZA) is indicated to treat moderate/severe menopausal vasomotor symptoms and prevent postmenopausal osteoporosis. This analysis examines the impact of the most bothersome vaginal symptom at baseline on effects of CE/BZA. Methods This post hoc analysis used data from a 12-week clinical trial of nonhysterectomized postmenopausal women (n = 664) randomly assigned to double-blind treatment with CE/BZA (0.45/20 mg and 0.625/20 mg), BZA 20 mg, or placebo. At baseline, women indicated which moderate/severe vaginal symptom (dryness, itching/irritation, or pain with intercourse) bothered them most. Repeated measures models were used to explore treatment effects in relationship to the most bothersome symptom. We calculated effect sizes for treatment differences versus placebo (effect sizes: trivial, 0.1; small, 0.2; medium, 0.5; large, 0.8). Results At baseline, 52% of women selected pain with intercourse, 35% selected vaginal dryness, and 13% selected vaginal itching/irritation as most bothersome. For these three symptom groups respectively, CE/BZA was associated with statistically significant improvements in Menopause-Specific Quality of Life sexual functioning (effect size: 0.45/20 mg, -0.36, -0.30, -0.67; 0.625/20 mg, -0.37, -0.40, -0.26) and/or overall score (effect size: 0.45/20 mg, -0.29, -0.41, -0.78; 0.625/20 mg, -0.41, -0.48, -0.68). Both those doses significantly improved the ease of lubrication item on the Arizona Sexual Experiences Scale in those with pain with intercourse (effect size: 0.45/20 mg, -0.43; 0.625/20 mg, -0.50) and produced some statistically significant improvements in vaginal cell counts in women with dryness or pain with intercourse as the most bothersome symptom. The higher dose was associated with greater treatment satisfaction on the Menopause Symptoms Treatment Satisfaction Questionnaire versus placebo in women who selected pain with intercourse (effect size: 0.40) or dryness (effect size: 0.43) as most bothersome. Conclusions The approved dose of CE/BZA had clear benefits, particularly in women with pain with intercourse (the most common bothersome symptom), in whom it improved lubrication, superficial cell counts, and sexual functioning.

The objectives of this study are to describe the implementation process of the Women’s Health Assessment Tool/Clinical Decision Support toolkit and summarize patients’ and clinicians’ perceptions of the toolkit. The Women’s Health Assessment Tool/Clinical Decision Support toolkit was piloted at three clinical sites over a 4-month period in Washington State to evaluate health outcomes among mid-life women. The implementation involved a multistep process and engagement of multiple stakeholders over 18 months. Two-thirds of patients (n = 76/110) and clinicians (n = 8/12) participating in pilot completed feedback surveys; five clinicians participated in qualitative interviews. Most patients felt more prepared for their annual visit (69.7%) and that quality of care improved (68.4%) while clinicians reported streamlined patient visits and improved communication with patients. The Women’s Health Assessment Tool/Clinical Decision Support toolkit offers a unique approach to introduce and address some of the key health issues that affect mid-life women.

Aim: To evaluate outcomes after implementing the women's health assessment tool (WHAT) and clinical decision support toolkit during annual well-women visits. Methods: An observational project involved women aged 45–64 years attending one of three medical sites in Washington (WA, USA). Responses to the WHAT questionnaire and patients' health resource utilization prepost toolkit implementation were analyzed. Results: A total of 110 women completed the WHAT questionnaire. Majority of women were postmenopausal (77.3%) and experienced depressive mood (63.6%), hot flashes (61.8%) or anxiety (60.9%) in the last 3 months. There was a 72.2% increase in the number of diagnoses made during the annual visit versus the previous 12 months. Conclusion: The WHAT/clinical decision support toolkit helped identify conditions relevant to mid-life women.

Background and Aims: This mediation modelling analysis evaluated direct and indirect effects of tofacitinib, an oral, small molecule Janus kinase inhibitor under investigation for ulcerative colitis, on patient treatment satisfaction. Methods: Data from an 8-week randomised Phase 2 trial ([NCT00787202][1]) in adults with moderate-to-severe, active ulcerative colitis receiving twice-daily tofacitinib 0.5-15 mg (n=146), or placebo (n=48) were analysed in patient-reported (n=149) and clinician-reported (n=170) outcomes-based mediation models. Binary predictor variable: treatment (pooled active treatment vs placebo). Eventual dependent variable: Week 8 patient treatment satisfaction (measured on a 5-point Likert scale). Mediators of treatment effect on satisfaction: Week 8 Inflammatory Bowel Disease Questionnaire domains (Bowel Symptoms, Emotional Health, Social Function and Systemic Symptoms) and Mayo scale domains (Stool Frequency, Rectal Bleeding, Physician's Global Assessment and Endoscopic Disease Activity) for patient-reported and clinician-reported models, respectively. Results: Overall tofacitinib indirect effect on satisfaction via Inflammatory Bowel Disease Questionnaire domains was 40.5% (P

Background:Symptomatic osteoarthritis (OA) leads to functional limitations and loss of independence. OA management focuses on pain relief and preserving physical function using non-pharmacologic and pharmacologic therapy. Additionally, patients commonly manage OA pain by avoiding activities that exacerbate their pain. Informal care, i.e. assistance from an unpaid caregiver, plays a major role in the total care provided to patients with chronic diseases like OA.Objectives:To evaluate how OA pain severity affects physical functioning and the subsequent need for assistance with mobility and daily activities in 5 EU countries: France, Germany, Italy, Spain and UK.Methods:Data were drawn from the Adelphi OA Disease Specific Programme (2017-18), a point-in-time study of physicians and their OA patients. Patients rated their average pain intensity over the last week on a 0-10 scale (0 = no pain; 10 = worst possible pain) and were then categorised into mild (0-3), moderate (4-6) and severe (7-10) pain groups. Patients also provided an assessment of their physical function (0-10 WOMAC scale where higher scores indicated greater functional impairment), impact on mobility, whether caregiver assistance was required, daily activities requiring caregiver assistance and home modifications made due to their OA. Physicians also rated patients’ functioning on a 0 to 10 scale (0 = fully functional; 10 = completely impaired). Comparisons among pain severity groups were made using chi-squared tests and analysis of variance.Results:The analysis included 1750 OA patients: 24% mild pain (n=413); 47% moderate pain (n=822); 29% severe pain (n=515). The patients were predominantly women (58%) and had a mean (SD) age of 65.6 (11.5).Increased pain severity was associated with greater functional impairment scores as reported by patients (WOMAC scores: mild pain=2.1; moderate pain=4.1; severe pain=5.9) and physician-rated functional impairment (mild pain=3.5; moderate pain=4.3; severe pain=5.6). Mobility was impacted for 78% of patients with severe pain (vs. 41% mild; 63% moderate) and the need for a walking aid such as a walking stick or walking frame increased with worsening severity; wheelchair assistance was needed for 7% of severe patients (compared with The need for assistance from a caregiver to help with daily activities was associated with an increase in patients’ pain (9% mild; 20% moderate; 42% severe [pConclusion:In this study of European patients, increased pain severity was associated with greater functional impairment and impact on mobility as expected; however, this study highlights the substantial need for assistance with daily activities as well as modifications to the home. The unseen costs to the patient with moderate to severe OA pain are significant.Disclosure of Interests:Philip G Conaghan Consultant of: AbbVie, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, GSK, Novartis, Pfizer, Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Lucy Abraham Shareholder of: Pfizer, Employee of: Pfizer, Peita Graham-Clarke Shareholder of: Eli Lilly and Co, Employee of: Eli Lilly and Co, Lars Viktrup Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Craig Beck Shareholder of: Pfizer, Employee of: Pfizer, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Niall Hatchell: None declared, Emily Clayton: None declared, James Jackson: None declared

Background:PsA is a chronic, systemic inflammatory disease with signs and symptoms across multiple domains, including cutaneous manifestations, which can impact health-related quality of life (HQoL). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. In two Phase 3 randomised studies, patients (pts) with active PsA treated with tofacitinib experienced greater improvements in various dermatologic endpoints, compared with placebo. As pruritus is a bothersome symptom of skin disease in pts with PsA, we sought to determine how tofacitinib affects HQoL via clinical improvements in skin symptoms including itch.Objectives:To determine the relationships between tofacitinib treatment, dermatologic symptoms and pt-reported HQoL related to skin disease in PsA.Methods:Analyses used data (mean scores from Months 1 and 3) from two Phase 3 studies (OPAL Broaden [NCT01877668]; OPAL Beyond [NCT01882439]) of pts with active PsA treated with tofacitinib 5 mg twice daily or placebo; pts were tumour necrosis factor inhibitor (TNFi)-naïve or had previous inadequate response (IR) to ≥1 TNFi. All pts were treated continuously with a single conventional synthetic DMARD. Mediation modelling, a statistical method used to assess mechanisms underlying observed relationships between different variables via other explanatory variables (mediators), was applied. The mediation model included: treatment, as the independent (explanatory) binary variable (tofacitinib 5 mg BID vs placebo); HQoL, measured by Dermatology Life Quality Index (DLQI), as the dependent (outcome) variable; and two mediators, pt-reported Itch Severity Index (ISI) and Physician’s Global Assessment of Psoriasis (PGA-PsO) (a latent variable represented by erythema, induration and scaling). The initial model designated the treatment effect on DLQI mediated via ISI and PGA-PsO as an indirect effect, and treatment effects not attributable to ISI or PGA-PsO as a direct effect (Figure 1).Results:Data were collected from 468 pts, pooled from both studies. In the initial model (pooled data), the effect of tofacitinib treatment on DLQI was largely mediated by itch (measured by ISI) and PGA-PsO (indirect effect) (pConclusion:Dermatology-focused mediation modelling showed that a majority of the effect (~80%) of tofacitinib treatment on DLQI is mediated by improvements in itch, with ~20% mediated via improvements in PGA-PsO.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Pamela Young Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rebecca Germino Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph F. Merola Consultant of: Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB Pharma, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and LEO Pharma, Gil Yosipovitch Grant/research support from: Galderma, Kiniksa, Leo, Menlo, Novartis, Pfizer, Sanofi Regeneron, Consultant of: Eli Lilly, Galderma, Kiniksa, Leo, Menlo Therapeutics, Novartis, Pfizer Inc, Sanofi Regeneron, Trevi, Sienna

Background:Joint pain is the most prevalent symptom for sufferers of osteoarthritis (OA). Pharmacological management of OA is restricted by limited efficacy and considerable toxicity, with growing fears about opioid use.Objectives:To understand the current real-world prescribed drug treatment paradigm related to OA disease severity for patients in 5 EU countries; France, Germany, Italy, Spain and the UK.Methods:Data were drawn from the Adelphi OA Disease Specific Programme (2017-18), a point-in-time study of physicians and their patients. Physicians classified their patients as currently having mild, moderate or severe disease severity, and provided details on currently prescribed OA therapy and physician satisfaction with therapy, rated from very satisfied to very dissatisfied. Patients were excluded from these analyses if they suffered from back and neck OA only, and shoulder OA that had not been diagnosed by X-ray. Comparisons among disease severity groups were made using analysis of variance and chi-squared tests.Results:The study included 489 physicians (primary care physicians, rheumatologists, orthopaedists) reporting on 3596 of their OA patients: 24% mild (n=874), 53% moderate (n=1904), and 23% severe (n=818). Overall, 73% patients were prescribed at least one drug for their OA (65% of mild; 76% of moderate; 77% of severe patients [Table 1.Prescribed treatment by physician-reported OA severityMild(n=874)Moderate(n=1904)Severe(n=818)Current class of medication prescribed for OA, n (%)Paracetamol186 (21.3)663 (34.8)313 (38.3)NSAIDs267 (30.5)605 (31.8)237 (29.0)Any opioid93 (10.6)501 (26.3)386 (47.2)Weak opioid82 (9.4)407 (21.4)255 (31.2)Strong opioid11 (1.3)99 (5.2)146 (17.8)Opioid + analgesic (combined)6 (0.7)15 (0.8)7 (0.9)Corticosteroid31 (3.5)150 (7.9)92 (11.2)Glycosaminoglycan50 (5.7)149 (7.8)62 (7.6)Viscosupplement12 (1.4)93 (4.9)42 (5.1)Number of currently prescribed drug classes, mean (SD)0.9 (0.8)1.4 (1.1)1.6 (1.2)Conclusion:Physicians reported decreasing satisfaction with treatment for their OA patients as disease severity increased, despite increasing use of opioids and numbers of classes of prescribed drugs.Disclosure of Interests:Philip G Conaghan Consultant of: AbbVie, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, GSK, Novartis, Pfizer, Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Lucy Abraham Shareholder of: Pfizer, Employee of: Pfizer, Peita Graham-Clarke Shareholder of: Eli Lilly and Co, Employee of: Eli Lilly and Co, Lars Viktrup Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Craig Beck Shareholder of: Pfizer, Employee of: Pfizer, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Niall Hatchell: None declared, Emily Clayton: None declared, James Jackson: None declared

Background:Osteoarthritis (OA) is a chronic joint disease associated with pain and impaired activity. With increasing obesity trends and an ageing population, the prevalence of OA is expected to rise in the future. This represents an increasing societal problem which will lead to an increased burden on healthcare services.Objectives:To understand the pattern of healthcare resource utilisation (HCRU) across France, Germany, Italy, Spain and the UK, as OA disease severity increases.Methods:Data were drawn from the Adelphi OA Disease Specific Programme (2017-18), a point-in-time study of physicians and their OA patients. OA disease severity was reported by physicians, who categorised patients’ OA severity as mild, moderate or severe. Patients were excluded from the analyses if they suffered from back and neck OA only, and shoulder OA that had not been diagnosed by X-ray. Physicians provided information, on a patient record form, about OA-related visits to healthcare professionals (HCPs), tests/scans conducted, emergency room (ER) visits and surgeries. Statistical comparisons among disease severity groups were made by analysis of variance and chi-squared tests.Results:The study included 489 physicians (primary care physicians, rheumatologists, orthopaedists) reporting on 3596 of their patients with OA: 24% mild (n=874), 53% moderate (n=1904) and 23% severe (n=818). Over the last 12 months, the mean number of consultations with HCPs increased with disease severity (3.7 mild, 4.2 moderate and 5.7 severe [Table 1.Physician-reported healthcare burden by OA disease severityMild(n=874)Moderate(n=1904)Severe(n=818)Number of patient visits to ER in the last 12 months, mean (SD)0.1 (0.4)0.1 (0.6)0.5 (1.0)Patients with ≥1 emergency visit in the last 12 months, n (%)13 (1.5)43 (2.3)79 (9.7)Patients with ≥1 hospitalisation in the last 12 months, n (%)11 (0.1)9 (0.5)26 (3.2)Number of patient outpatient hospital visits in the last 12 months, mean (SD)0.5 (1.4)0.6 (1.1)1.2 (1.4)Conclusion:This real-world data demonstrated an increase in visits to HCPs, monitoring tests and scans, hospitalisations, ER visits and surgery as OA disease severity worsened.Disclosure of Interests:Philip G Conaghan Consultant of: AbbVie, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, GSK, Novartis, Pfizer, Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Lucy Abraham Shareholder of: Pfizer, Employee of: Pfizer, Peita Graham-Clarke Shareholder of: Eli Lilly and Co, Employee of: Eli Lilly and Co, Lars Viktrup Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Craig Beck Shareholder of: Pfizer, Employee of: Pfizer, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Niall Hatchell: None declared, Emily Clayton: None declared, James Jackson: None declared

Background:With multiple disease domains affected in PsA, clinical and patient-reported outcome (PRO) measures are important to assess disease improvement following treatment. Rapid, meaningful improvements in disease activity are a priority for physicians and patients (pts). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Higher proportions of pts achieved responses in PROs and clinical measures when treated with tofacitinib for 3 months vs placebo (PBO).1-5Proportions of responders were also similar between tofacitinib and adalimumab (ADA) after 3, 6 and 12 months.2,3,5Objectives:To determine the time to initial response using responder definitions for selected PROs and clinical endpoints in pts with active PsA treated with tofacitinib, ADA or PBO switching to tofacitinib.Methods:In this post hoc analysis, data were collected from two Phase 3 studies (OPAL Broaden [12 months;NCT01877668]; OPAL Beyond [6 months;NCT01882439]).3,4Pts receiving tofacitinib 5 or 10 mg twice daily (BID), subcutaneous ADA 40 mg once every two weeks (Q2W; OPAL Broaden only), or PBO switching to tofacitinib 5 or 10 mg BID at Month (M)3, were included. Responder definitions included: HAQ-DI ≥0.35-point improvement from baseline (BL), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score ≥4-point improvement from BL, minimal disease activity (MDA) yes/no composite response (meeting at least 5 of 7 criteria) and PsA Disease Activity Score (PASDAS) post-BL score of ≤3.2 and >1.6-point improvement from BL. First post-BL data were collected at Week 2 (eg for HAQ-DI) or M1. Time-to-event analyses were performed using the Kaplan-Meier (KM) method, with pts censored at the last observed visit. Log-rank tests compared time to initial response across treatment groups.Results:KM analyses show days to initial response (Figure 1, Figure 2). Time to initial HAQ-DI response was significantly different between treatment groups in OPAL Broaden (pConclusion:Times to initial response in functional ability and disease activity were similar in pts treated with either tofacitinib or ADA. Time to initial response prior to first post-BL observation (Week 2 or M1) was not estimable in this analysis. These results may help physicians better understand the time frame for a meaningful response in pts receiving tofacitinib.References:[1]Strand et al. RMD Open 2019;5:e000808.[2]Strand et al. RMD Open 2019;5:e000806.[3]Mease et al. NEJM 2017;377:1537-50.[4]Gladman et al. NEJM 2017;377:1525-36.[5]Helliwell et al. Arthritis Res Ther 2018;20:242.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Laura C Coates: None declared, Joseph Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ming-Ann Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Elizabeth Bacci Employee of: Evidera, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Philip Helliwell: None declared

Background The Short Form-36 Health Survey version 2 (SF-36v2) is a generic health-related quality-of-life (HRQoL) instrument [1]. Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). In these exploratory analyses the concordance between total and partial Mayo scores and SF-36v2 scores was evaluated in patients with UC in the Phase 3 tofacitinib 8-week OCTAVE Induction 1&2 (NCT01465763; NCT01458951) and 52-week OCTAVE Sustain (NCT01458574) studies. Methods A repeated measures regression model was used to evaluate the relationship between total and partial Mayo scores (as predictor) and SF-36v2 component and domain scores. A sensitivity analysis to assess the linearity assumption was performed using Mayo score as a categorical anchor (represented by integer values 0–12 [total] or 0–9 [partial]). Previous analyses identified clinically important differences (CIDs) in total and partial Mayo scores as changes of 3 points and 2.25 points, respectively [2]. Mean differences in SF-36v2 component and domain scores were compared with their recommended group-level CID thresholds [3]. Results Clinically meaningful differences of 3 points and 2.25 points in total and partial Mayo scores, respectively, were generally associated with clinically meaningful differences in SF-36v2 component and domain scores, with the exception of Role-Emotional with partial Mayo score in the pooled induction studies and with total Mayo score in the maintenance study. In the induction studies, a 3-point difference in total Mayo score was associated with a mean difference exceeding CIDs in both the SF-36v2 Physical Component Summary score (mean improvement 4.5; 95% confidence interval [CI] 4.2, 4.7) and Mental Component Summary score (mean improvement 5.0; 95% CI 4.6, 5.3). Results were closely aligned when Mayo score was used as a categorical or continuous anchor, supporting a linear relationship between Mayo score and SF-36v2 scores (Figure). Similar results were observed in the maintenance study, and when assessing the relationship of partial Mayo score with SF-36v2 scores. Conclusion Clinically meaningful decreases in disease activity, as measured by Mayo score, were associated with clinically meaningful benefits in HRQoL, as measured by SF-36v2 component and domain scores. These findings highlight the impact that disease activity has on HRQoL and may assist with articulating the treatment effect of tofacitinib on specific domains. References

Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). In patients with UC, associations between endoscopic findings and patient-reported outcomes, such as stool frequency (SF) and rectal bleeding (RB), are not well described. Here, we evaluated the diagnostic accuracy of Mayo SF and RB subscores to predict mucosal healing (MH) in OCTAVE Induction 1 and 2 (NCT01465763; NCT01458951). Methods This post hoc analysis used data from OCTAVE Induction 1 and 2, two identical, randomised, placebo-controlled, 8-week, Phase 3 studies of tofacitinib for the treatment of patients with moderately to severely active UC.1 SF (Mayo subscore 0–3), RB (Mayo subscore 0–3) and endoscopic findings (Mayo endoscopic subscore [ES] 0–3) were assessed at baseline and at Week 8. MH and endoscopic normalisation were defined as an ES of 0 or 1, or an ES of 0, respectively. Based on two-by-two contingency tables, diagnostic test characteristics for SF and RB were evaluated: positive and negative predictive values, sensitivity and specificity. Kappa statistics (chance-corrected measure of agreement) and Pearson correlations (a measure of association) were also calculated. All available data at Week 8 were used. Results A total of 614 and 547 patients received treatment (tofacitinib 15 or 10 mg BID, or placebo) in OCTAVE Induction 1 and 2, respectively. Two-by-two contingency table analyses showed that dichotomised SF (0 vs. ≥1) and RB (0 vs. ≥1) were each or both not good predictors of MH (ES of 0 or 1 vs. ≥2) or endoscopic normalisation (ES 0 vs. ≥1), as ≥1 of the four diagnostic test characteristics was Conclusion In patients with UC treated with tofacitinib or placebo in OCTAVE Induction 1 and 2, SF and RB subscores had slight-to-moderate agreement with ES, but were not predictive of MH or endoscopic normalisation. The presence of blood at Week 8 strongly indicated that patients had endoscopic activity, but the absence of blood was associated with MH in Reference

Background Pruritus is a leading cause of reduced health-related quality of life (QoL) in atopic dermatitis (AD). Crisaborole ointment is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD. In identical Phase 3 studies (NCT02118766, NCT02118792), crisaborole reduced disease and pruritus severity versus vehicle. Objective Quantify the relationship between pruritus and QoL using data from these studies. Methods Patients aged ≥2 years were randomly assigned 2 : 1 to receive crisaborole:vehicle twice daily for 28 days. QoL was measured at baseline and day 29 using the Dermatology Life Quality Index (DLQI; patients aged ≥16 years), the Children's Dermatology Life Quality Index (CDLQI; patients aged 2-15 years) and the Dermatitis Family Impact (DFI; caregivers of patients aged 2-17 years). Pruritus was measured using the Severity of Pruritus Scale (SPS), a 4-point scale from 0 ('no itching') to 3 ('bothersome itching/scratching that disturbs sleep'), and captured morning and evening via electronic diary. Data from crisaborole and vehicle arms were pooled for this analysis. A repeated-measures longitudinal model was used to estimate relationships between pruritus (SPS) and QoL (DLQI, CDLQI and DFI in separate analyses). Results One thousand five hundred and twenty two patients received crisaborole or vehicle. A linearity assumption for the relationship between SPS and DLQI (n = 294), CDLQI (n = 1200), and DFI (n = 1293) was appropriate. For DLQI, SPS score of 0 was associated with 'no negative effect on patient QoL'; SPS score of 1 was associated with 'small effect on patient QoL'; SPS score of 2 was associated with 'moderate effect on patient QoL'; and SPS score of 3 was associated with 'very large effect on patient QoL'. The pattern of relationships between SPS and CDLQI and DFI was similar. Conclusions The relationships between SPS and DLQI, CDLQI and DFI substantiate the significant link between pruritus and patient/caregiver QoL in AD.

Postmenopausal (PM) women taking therapies using estrogens plus progestogens (EPTs) can experience side effects (breast pain, vaginal spotting/bleeding). Sensitivity of the European Quality of Life Five Dimension Five Level (EQ-5D-5L) in measuring quality of life of PM women experiencing side effects of EPTs is unknown. A crosswalk between the Menopause-Specific Quality of Life (MENQOL) questionnaire and the EQ-5D-5L was assessed.The measures were administered to 352 PM women (side effects = 202; control = 75; untreated = 75) in a non-interventional study. MENQOL total scores, treated as continuous and categorical predictors, were mapped onto EQ-5D-5L utilities using regression. Ordinary least-squares regression using averaged scores over time, goodness of fit, and estimated coefficients was also assessed.Mean age was 53.7 years. The first model (MENQOL as a continuous variable) showed a moderate correlation (-0.589) and statistically significant relationship with the EQ-5D-5L (p 0.001), with an equation of EQ-5D-5L = 0.992 - 0.042 × MENQOL. The EQ-5D-5L mean scores were comparable (side effects = 0.854; control = 0.927; untreated = 0.836) to MENQOL mean scores estimated in the first model (side effects = 0.865 [standard deviation 0.07]; control = 0.909; untreated = 0.833). Linearity assumptions were supported with MENQOL scores as a categorical predictor. Goodness of fit was moderate (RThe crosswalk supports conversion of MENQOL scores to EQ-5D-5L-derived health utilities for group-level analyses in PM women.