Improvements in Disease Activity Partially Mediate the Effect of Tofacitinib Treatment on Generic and Disease-Specific Health-Related Quality of Life in Patients with Ulcerative Colitis: Data from the OCTAVE Program.

BACKGROUND: Patients with ulcerative colitis (UC) often report impaired health-related quality of life (HRQoL). Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of UC. In addition to previous demonstrations of improved clinical measures (e.g., Mayo score), tofacitinib has been shown to improve HRQoL in patients with UC. This analysis explored the interrelationships among tofacitinib treatment, HRQoL, and disease activity (measured using Mayo subscores) using mediation modeling. METHODS: Data were collected from two 8-week induction studies (OCTAVE Induction 1 and 2) in patients with moderate to severe UC treated with tofacitinib or placebo. Two mediation models were specified. First, Mayo subscores were mediators between the binary treatment variable (tofacitinib vs. placebo) and the eight Short Form-36 Health Survey (SF-36) domain scores as outcomes. Second, the four Inflammatory Bowel Disease Questionnaire (IBDQ) domain scores served as outcomes. Both models used data collected at week 8. RESULTS: Overall, 1,073 and 1,079 patients were included in the SF-36- and IBDQ-based models, respectively. For all SF-36 domains, improvements in Mayo subscores were estimated to explain 65.6% (bodily pain) to 92.9% (mental health) of the total treatment effect on SF-36 domain scores (all p < 0.05). For all IBDQ domains, improvements in Mayo subscores explained 71.6% (systemic symptoms) to 84.7% (emotional function) of the total treatment effect (all p < 0.05). CONCLUSION: Mayo scores and Mayo subscores are significant but incomplete contributors to tofacitinib's effect on HRQoL in patients with moderate to severe UC. CLINICALTRIALS: gov: NCT01465763; NCT01458951.

Meaningful within-patient change for clinical outcome assessments: model-based approach versus cumulative distribution functions.

OBJECTIVES: The FDA recommends the use of anchor-based methods and empirical cumulative distribution function (eCDF) curves to establish a meaningful within-patient change (MWPC) for a clinical outcome assessment (COA). In practice, the estimates obtained from model-based methods and eCDF curves may not closely align, although an anchor is used with both. To help interpret their results, we investigated and compared these approaches. METHODS: Both repeated measures model (RMM) and eCDF approaches were used to estimate an MWPC on a target COA. We used both real-life (ClinicalTrials.gov: NCT02697773) and simulated data sets that included 688 patients with up to six visits per patient, target COA (range 0 to 10), and an anchor measure on patient global assessment of osteoarthritis from 1 (very good) to 5 (very poor). Ninety-five percent confidence intervals for the MWPC were calculated by the bootstrap method. RESULTS: The distribution of the COA score changes affected the degree of concordance between RMM and eCDF estimates. The COA score changes from simulated normally distributed data led to greater concordance between the two approaches than did COA score changes from the actual clinical data. The confidence intervals of MWPC estimate based on eCDF methods were much wider than that by RMM methods, and the point estimate of eCDF methods varied noticeably across visits. CONCLUSIONS: Our data explored the differences of model-based methods over eCDF approaches, finding that the former integrates more information across a diverse range of COA and anchor scores and provides more precise estimates for the MWPC.

Concern about addiction is associated with lower quality of life in patients with osteoarthritis: an exploratory, real-world data analysis.

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 < 0.0001). 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.

Factors associated with physician-reported treatment status of patients with osteoarthritis pain.

BACKGROUND: Osteoarthritis (OA) is typically associated with pain, but many patients are not treated. METHODS: This point in time study explored factors associated with treatment status, using logistic regression of data from the Adelphi OA Disease Specific Programme conducted in the United States. Patients' treatment status was based on physician-reported, current: 1) prescription medication for OA vs. none; and 2) physician treatment (prescription medication and/or recommendation for specified nonpharmacologic treatment for OA [physical or occupational therapy, acupuncture, transcutaneous electrical nerve stimulation, or cognitive behavior therapy/psychotherapy]) vs. self-management (no prescription medication or specified nonpharmacologic treatment). RESULTS: The 841 patients (including 57.0% knee OA, 31.9% hip OA) reported mild (45.4%) or moderate or severe (54.6%) average pain intensity over the last week. The majority were prescribed medication and/or recommended specified nonpharmacologic treatment; 218 were not prescription-medicated and 122 were self-managed. Bivariate analyses showed less severe patient-reported pain intensity and physician-rated OA severity, fewer joints affected by OA, lower proportion of joints affected by knee OA, better health status, lower body mass index, and lower ratings for cardiovascular and gastrointestinal risks, for those not prescribed medication (vs. prescription-medicated). Multivariate analyses confirmed factors significantly (p < 0.05) associated with prescription medication included (odds ratio): physician-rated current moderate OA severity (vs. mild, 2.03), patient-reported moderate OA severity 6 months ago (vs. mild, 1.71), knee OA (vs. not, 1.81), physician-recommended (0.28) and patient-reported (0.43) over-the-counter medication use (vs. not), prior surgery for OA (vs. not, 0.37); uncertain income was also significant. Factors significantly (p < 0.05) associated with physician treatment included (odds ratio): physician-recommended nonpharmacologic therapy requiring no/minimal medical supervision (vs. not, 2.21), physician-rated current moderate OA severity (vs. mild, 2.04), patient-reported over-the-counter medication use (vs. not, 0.26); uncertain time since diagnosis was also significant. Patient-reported pain intensity and most demographic factors were not significant in either model. CONCLUSIONS: Approximately 1 in 4 patients were not prescribed medication and 1 in 7 were self-managed, although many were using over-the-counter medications or nonpharmacologic therapies requiring no/minimal medical supervision. Multiple factors were significantly associated with treatment status, including OA severity and over-the-counter medication, but not pain intensity or most demographics.

Burden of chronic low back pain: Association with pain severity and prescription medication use in five large European countries.

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.

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

OBJECTIVES: Although the osteoarthritis (OA) burden is well-recognised, the benefit of currently available OA pharmacological therapy is not clear. This study aimed to assess whether the impact of OA pain on health-related quality of life (HRQoL), work, and healthcare resource utilisation (HRU) differed by both pain severity and prescription medication status. METHODS: This cross-sectional study used pooled data from the 2016/2017 European National Health and Wellness Survey. Respondents with self-reported physician-diagnosed OA and pain were included. Outcomes examined included HRQoL, health utility, health status, work productivity and activity impairment, and HRU. Groups derived from self-reported pain severity and prescription medication use were compared using chi-square tests, analysis of variance, and generalised linear models controlling for socio-demographics, health behaviours, and health status. RESULTS: Respondents with OA (n=2417) reported mild (40.4%, of which 44.9% prescription-treated) and moderate to severe pain (59.6%, of which 54.0% prescription-treated). HRQoL, health utility, health status, and work and activity impairment were substantially worse among the moderate/severe pain prescription-treated group compared to the rest (e.g. SF-12v2 physical component score [PCS] for moderate/severe pain prescription-treated=34.5 versus mild pain prescription-treated =39.3, moderate/severe pain prescription-untreated=40.6, and mild pain prescription-untreated=45.6; p<0.01). HRU such as the mean number of emergency room visits for >6 months was higher in the prescription-treated groups (0.51-0.52, 95% CI 0.437-0.71) than the prescription-untreated groups (0.30-0.34, 95% CI 0.21-0.46; p<0.05). CONCLUSIONS: Persons with moderate to severe OA pain treated with available prescription medications have poor health status and HRQoL and increased HRU compared to those not receiving prescription medications.

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

Patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML) can be effectively treated with tyrosine kinase inhibitors (TKIs) and achieve a lifespan similar to the general population. The success of TKIs, however, requires long-term and sometimes lifelong treatment; thus, patient-assessed health-related quality of life (HRQoL) has become an increasingly important parameter for treatment selection. Bosutinib is a TKI approved for CP CML in newly diagnosed adults and in those resistant or intolerant to prior therapy. In the Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment (BFORE), bosutinib demonstrated a significantly higher major molecular response rate compared with imatinib, with maintenance of HRQoL (measured by the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire), after 12 months of first-line treatment. We examined relationships between molecular response (MR) and HRQoL. MR values were represented by a log-reduction scale (MRLR; a continuous variable). A repeated-measures longitudinal model was used to estimate the relationships between MRLR as a predictor and each FACT-Leu domain as an outcome. Effect sizes were calculated to determine strength of effects and allow comparisons across domains. The majority of FACT-Leu domains (with the exception of social well-being and physical well-being) demonstrated a significant relationship with MRLR (p < 0.05). Our results showed variable impact of clinical improvement on different dimensions of HRQoL. For patients who achieved MR5, emotional well-being and leukemia-specific domains showed the greatest improvement, with medium differences in effect sizes, whereas social well-being and physical well-being had the weakest relationship with MR.

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

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.

Direct and Indirect Effects of Crisaborole Ointment on Quality of Life in Patients with Atopic Dermatitis: A Mediation Analysis.

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) and 72% (CDLQI model, p < 0.05). Direct effect (other effects) on QoL was 49% (DLQI model, p < 0.05) and 28% (CDLQI model, p > 0.05). Mediation modeling shows that crisaborole affects QoL mostly indirectly through pruritus severity reduction.

A multi-item Physician Global Assessment scale to assess psoriasis disease severity: validation based on four phase III tofacitinib studies.

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.

Important Group Differences on the Functional Assessment of Cancer Therapy-Kidney Symptom Index Disease-Related Symptoms in Patients with Metastatic Renal Cell Carcinoma.

BACKGROUND: The Functional Assessment of Cancer Therapy-Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS) is important to gauge clinical benefit in metastatic renal cell carcinoma (mRCC). OBJECTIVES: To estimate important difference (ID) in FKSI-DRS scores that is considered to be meaningful when comparing treatment effect between groups, using mRCC trial data. METHODS: Data were derived from two pivotal phase III mRCC trials comparing sunitinib versus interferon alfa (N = 750) in first-line mRCC, and axitinib versus sorafenib (N = 723) in second-line mRCC. The change from baseline in FKSI-DRS score was examined as a function of a set of anchors using the repeated-measures model. Several anchors were evaluated: FKSI item "I am bothered by side effects of treatment," EuroQol five-dimensional questionnaire utility score, and adverse events. RESULTS: When the "I am bothered by side effects of treatment" score was used as an anchor, the ID ranged between 1.2 and 1.3 points. When change in the EuroQol five-dimensional questionnaire utility score was used as an anchor, the FKSI-DRS ID ranged between 0.62 and 0.63 points. Selecting the adverse events that corresponded to a maximum worsening in the FKSI-DRS score in either trial, the ID ranged between 0.62 and 0.74 points. CONCLUSIONS: Among patients undergoing treatment for mRCC, between-group differences in FKSI-DRS scores as low as 1 point might be meaningful.

Psychometric validation of the SF-36® Health Survey in ulcerative colitis: results from a systematic literature review.

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Validation of the Itch Severity Item as a Measurement Tool for Pruritus in Patients with Psoriasis: Results from a Phase 3 Tofacitinib Program.

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.

Quantifying Barriers to Improvement of Treatment Satisfaction in Men With Erectile Dysfunction: Use of Person-Item Maps.

INTRODUCTION: Patient-reported outcomes are a valuable tool used to gauge treatment satisfaction in different conditions, including erectile dysfunction (ED). AIM: To use person-item maps to quantify barriers to improvement of treatment satisfaction in men with ED. METHODS: Men 18 to 65 years old with documented ED received sildenafil 50 mg, sildenafil 100 mg, or placebo for 8 weeks in a double-blinded manner. Post hoc analyses were conducted on Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) data (11 items rating treatment satisfaction; each item score range = 0-4). MAIN OUTCOME MEASURES: Person-item maps were developed based on Rasch models. To quantify barriers to improvement of treatment satisfaction, responses to the 11 items of the EDITS questionnaire were dichotomized to indicate improvement (responses of 3 or 4 were combined to a score of 1) vs no change or worsening (responses of 0, 1, or 2 were combined to a score of 0). RESULTS: Analyses were conducted using data from 278 men who completed the EDITS questionnaire at the end of double-blinded treatment. The person-item map indicated that EDITS item 4 (ease of use of treatment) was the easiest barrier to overcome, whereas the most difficult barrier to improvement of treatment satisfaction was EDITS item 2 (degree to which treatment met expectations). Most men in the sildenafil 100-mg group endorsed most EDITS items, consistent with substantial improvement. The sildenafil 50-mg group was similar, but with smaller frequencies for endorsing improvement of the more difficult EDITS items. In contrast, men receiving placebo endorsed mainly the easiest EDITS items, with only a small number of men endorsing the difficult items. CONCLUSION: A person-item map is a useful means for quantifying barriers to improvement of treatment satisfaction represented by EDITS items in patients with ED.

Validation of overactive bladder questionnaire (1-week recall version) in medically complex elderly patients with overactive bladder.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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 of >1.96, and standardized path coefficients of >0.40. OAB-q domains demonstrated good internal consistency (CCA >0.7). 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. CONCLUSIONS: 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.

Randomized trial of tofacitinib in active ulcerative colitis: analysis of efficacy based on patient-reported outcomes.

BACKGROUND: Tofacitinib, a novel, oral Janus kinase inhibitor, demonstrated a dose-dependent efficacy for induction of clinical response and remission in patients with active ulcerative colitis (UC). The objective of the current study was to determine the effect of tofacitinib on patient-reported outcomes (PROs). METHODS: Eligible patients (≥18 years of age) with a diagnosis of active UC (total Mayo score of 6-12 points and moderately-to-severely active disease on sigmoidoscopy) were randomized in a 2:2:2:3:3 ratio to receive oral tofacitinib 0.5 mg, 3 mg, 10 mg, or 15 mg, or placebo twice daily (BID) for 8 weeks. PROs were assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Inflammatory Bowel Disease Patient-Reported Treatment Impact (IBD PRTI) survey. RESULTS: At Week 8, mean IBDQ total scores had improved relative to baseline across all five treatment groups (baseline range 123.2-134.5; Week 8 range 149.6-175.4). Improvement from baseline was significantly greater (P = 0.001) for tofacitinib 15 mg BID versus placebo. For tofacitinib 15 mg BID, most patients reported satisfaction or extreme satisfaction, definite preference for tofacitinib, and definite willingness to use tofacitinib again on the IBD PRTI at week 8. Patients achieving endoscopic remission (Mayo endoscopy score of 0) had significantly higher IBDQ scores and favorable PRTI scores than those not achieving endoscopic remission. CONCLUSIONS: Short-term treatment with tofacitinib BID was associated with dose-dependent improvement in health-related quality of life and patient preferences for tofacitinib. The results complement previously reported efficacy and safety data for the Phase II study. (NCT 00787202, November 6, 2008).

Prevalence of menopausal symptoms among mid-life women: findings from electronic medical records.

BACKGROUND: To assess the prevalence of menopausal symptoms among women prescribed hormone therapy (HT) using electronic medical record data from a regional healthcare organization. METHODS: Retrospective data from the Reliant Medical Group from 1/1/2006-12/31/2011 were assessed for 102 randomly-selected patients. Study eligibility criteria included: females aged 45 to 65; prescribed oral or transdermal HT; no history of breast cancer, venous thromboembolism, stroke, gynecological cancer, or hysterectomy; continuously enrolled in the health plan for 1 year before and after the first observed HT prescription. Prevalence of menopause-related symptoms was analyzed descriptively at both the patient and visit levels. RESULTS: Mean age of patients was 54 years. The most common menopausal symptoms were: hot flushes (40%), night sweats (17%), insomnia (16%), vaginal dryness (13%), mood disorders (12%), and weight gain (12%). Among the 102 patients, 163 individual visits listing menopausal symptoms were identified, of which hot flushes (71 visits) were the most common symptom identified. CONCLUSION: Our findings provide recent data on the types of menopausal symptoms experienced by mid-life women prescribed HT. Electronic medical records may be a rich source of data for future studies of menopausal symptoms in this population.

Characterizing fatigue associated with sunitinib and its impact on health-related quality of life in patients with metastatic renal cell carcinoma.

BACKGROUND: Using phase 3 trial data for sunitinib versus interferon (IFN)-α in treatment-naive patients with metastatic renal cell carcinoma, retrospective analyses characterized sunitinib-associated fatigue and its impact on patient-reported health-related quality of life (HRQoL). METHODS: Patients received sunitinib at a dose of 50 mg/day on a schedule of 4 weeks on/2 weeks off (375 patients) or IFN-α at a dose of 9 MU subcutaneously 3 times per week (360 patients). HRQoL was self-assessed using the Functional Assessment of Cancer Therapy-Kidney Symptom Index-15-item (FKSI-15) questionnaire, with fatigue assessed using its Disease-Related Symptoms subscale. Fatigue was also assessed by providers using Common Terminology Criteria for Adverse Events (CTCAE). A repeated-measures model (M1) and random intercept-slope model (M2) characterized sunitinib-associated fatigue over time. Another repeated-measures model examined the relationship between HRQoL scores and CTCAE fatigue grade. RESULTS: M1 demonstrated that the initial increase in patient-reported fatigue with sunitinib was worst during cycle 1, with mean values numerically better at subsequent cycles; most pairwise comparisons of consecutive CTCAE fatigue cycle means were not found to be statistically significant. M2 demonstrated that the overall trend (slope) for patient-reported and CTCAE fatigue with sunitinib was not statistically different from 0. The relationship between most HRQoL scores and CTCAE fatigue was close to linear regardless of treatment, with lower scores (worse HRQoL) corresponding to higher fatigue grade. The majority of HRQoL scores were better with sunitinib versus IFN-α for the same CTCAE fatigue grade. CONCLUSIONS: Patients reported worse fatigue during the first sunitinib cycle. However, in subsequent consecutive cycles, less fatigue was reported with no statistically significant worsening. CTCAE fatigue assessment may not fully capture patient treatment experience.

Time to improvement of pain, morning stiffness, fatigue, and disease activity in patients with ankylosing spondylitis treated with tofacitinib: a post hoc analysis.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Time to improvement in core domains of AS was estimated in tofacitinib-treated patients with AS. METHODS: This post hoc analysis used phase 3 trial data from patients with AS receiving tofacitinib 5 mg twice daily or placebo to week (W)16; all patients received open-label tofacitinib W16-48. OUTCOMES: nocturnal pain; total back pain; fatigue, spinal pain, peripheral joint pain/swelling, enthesitis, and morning stiffness (Bath AS Disease Activity Index [BASDAI] questions 1-6); BASDAI total score; AS Disease Activity Score (ASDAS). Median time to improvement events was estimated using non-parametric Kaplan-Meier models. Improvement events were defined as initial (first post-baseline observation) and continued (sustained for 2 consecutive visits) ≥ 30% and ≥ 50% improvement in back/nocturnal pain or BASDAI questions/total scores, or ASDAS improvement ≥ 1.1 and ≥ 2.0 points. RESULTS: 269 patients (tofacitinib: n = 133; placebo-to-tofacitinib: n = 136) were assessed. Median time to improvement was shorter, and more patients experienced improvements with tofacitinib vs. placebo-to-tofacitinib; differences observed from W2 (first post-baseline assessment). Median time to initial (continued) ≥ 30% pain improvement was 4 (4-8) weeks for tofacitinib vs. 24 (24) weeks for placebo-to-tofacitinib (8 [8] weeks post-switch). Median time to initial (continued) ≥ 50% improvement of pain, peripheral joint pain/swelling and enthesitis, morning stiffness, BASDAI total score, and fatigue was 8-24 (12-40) weeks with tofacitinib vs. 24-32 weeks (32 weeks-not estimable [NE]) with placebo-to-tofacitinib. Median time to initial (continued) ASDAS improvement ≥ 1.1 points was 4 (8) weeks for tofacitinib vs. 24 (24) weeks for placebo-to-tofacitinib, and NE for improvement ≥ 2.0 points with either treatment. CONCLUSIONS: Improvements in AS core domains occurred more rapidly with tofacitinib vs. placebo-to-tofacitinib. Half of tofacitinib-treated patients with AS will likely experience improvements ≥ 30% in pain and ≥ 1.1 points in ASDAS during month (M)1, ≥ 50% improvement in nocturnal pain and enthesitis by M2, and in morning stiffness by M3. Results show that initiating tofacitinib as soon as possible is associated with quicker improvements in AS core domains vs. delaying treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03502616, 11 April 2018.

Relationships of Work Productivity and Activity Impairment With Patient-Reported Outcomes in Ankylosing Spondylitis: Results From Two Trials.

OBJECTIVE: We examined the relationships of work productivity and activity impairment with key patient-reported outcomes (PROs) assessing pain, disease activity, and health-related quality of life (HRQoL) in patients with ankylosing spondylitis (AS). METHODS: This post hoc analysis pooled available data from baseline to end of the double-blind phase of phase 2 and 3 placebo-controlled tofacitinib trials in patients with active AS. A repeated-measures longitudinal model assessed the relationships (linear or nonlinear) between Work Productivity and Activity Impairment questionnaire in Spondyloarthritis (WPAI:SpA) domains (absenteeism, activity impairment, presenteeism, and productivity loss) as outcomes and key PROs (total back pain, nocturnal spinal pain, Patient Global Assessment of Disease Activity, AS Quality of Life, EuroQol 5-Dimension 3-Level [EQ-5D-3L], and EQ-5D Visual Analog Scale [EQ-5D-VAS]) as predictors. RESULTS: Data from 330 to 475 patients were available, depending on the analysis. Relationships between WPAI:SpA domains and PROs were approximately linear. The worst PRO scores were associated with a decline in patients' work capacity (measured by activity impairment, presenteeism, and productivity loss [>65%]); the best scores were associated with improvements in WPAI:SpA domains (8%-23%). Incremental PRO improvements were associated with improvement of activity impairment, presenteeism, and productivity loss. Relationships between absenteeism and PROs were the weakest, owing to absenteeism being low in the study population. CONCLUSION: Evidence of linear relationships between work productivity and activity impairment with patient-reported pain, disease activity, and HRQoL was observed. Interventions to control pain and disease activity and improve HRQoL are therefore likely to improve work productivity and reduce activity impairment in patients with AS.