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Progression-free survival (PFS) is a common primary endpoint in newly diagnosed multiple myeloma (NDMM). Patients with NDMM typically have longer PFS and are more likely to achieve minimal residual disease (MRD) or complete response (CR) compared to patients with relapsed or refractory multiple myeloma. Response-based surrogate endpoints may hold value given the longer follow-up time required to evaluate PFS in NDMM. In this work, systematic literature reviews of Medline, Embase, and Cochrane databases (2010-06/2020) and relevant congresses (2018–2020) were performed to identify randomized clinical trials (RCTs) and real-world studies in NDMM reporting median PFS and objective response. Associations between PFS and each response endpoint were evaluated using Pearson's product-moment correlation weighted by sample size in each RCT arm. Unadjusted and adjusted weighted linear regression models were applied to estimate the gain in median PFS associated with each response endpoint. Statistically significant correlations were identified for median PFS with overall response rate (ORR; Pearson r = 0.59), CR (r = 0.48), stringent CR (sCR; r = 0.68), and MRD (r = 0.69). The unadjusted models estimated 0.50 (95% CI: 0.36, 0.64; p<0.001), 0.42 (95% CI: 0.25, 0.58; p<0.001), 1.05 (95% CI: 0.58, 1.52; p<0.001), and 0.35 (95% CI: 0.12, 0.58; p = 0.006) months of median PFS gained per point of ORR, CR, sCR, and MRD, respectively. Associations for median PFS remained statistically significant in models adjusted for age and treatment type with ORR (0.35, 95% CI: 0.21, 0.49; p<0.001), and adjusted for age and International Staging System risk stage with CR (0.29, 95% CI: 0.16, 0.41; p<0.001). Due to small sample size, adjusted models could not be constructed for sCR or MRD. Nevertheless, evidence of significant survival benefit (p<0.05) associated with MRD negativity and sCR was identified across real-world studies. These findings provide support for the use of response outcomes as surrogate endpoints to estimate PFS benefit in NDMM. [ABSTRACT FROM AUTHOR]

Objective: Bosutinib, nilotinib and dasatinib are approved for the treatment of patients with newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML). In the absence of head-to-head comparisons between second-generation tyrosine kinase inhibitors (TKIs), the objective of this study was to indirectly compare the efficacy of bosutinib with nilotinib and dasatinib in first-line (1L) CP-CML.Methods: Cross-trial heterogeneity in terms of patient baseline characteristics and imatinib dose escalation are difficult to adjust for in network meta-analyses and anchored matching-adjusted indirect treatment comparisons (MAICs). Therefore, an unanchored MAIC was performed using patient level data from bosutinib (BFORE trial) and published aggregated data from nilotinib (ENESTnd) and dasatinib (DASISION) trials. After matching, cytogenetic and molecular responses, and disease progression, after a minimum follow-up of 24 months were compared between nilotinib versus bosutinb and dasatinib versus bosutinib.Results: The comparison of nilotinib versus bosutinib resulted in no statistically significant differences for MMR at and by 24 months, MR4 by 24 months, MR4.5 at and by 24 months, CCyR by 24 months, and disease progression, however, a decreased odds of MR4 at 24 months in favor of bosutinib versus nilotinib was observed. The comparison of dasatinib versus bosutinib by 24 months resulted in no statistically significant differences for MMR, disease progression, and CCyR, however a decreased odds of MR4.5 in favor of bosutinib versus dasatinib was observed.Conclusions: Overall, in these analyses bosutinib demonstrates equivalent efficacy to nilotinib and dasatinib in the treatment of patients with newly diagnosed CP-CML. [ABSTRACT FROM AUTHOR]

Background: Gemtuzumab ozogamicin (GO) was approved in 2017 in the US for the treatment of adults with newly diagnosed CD33-positive (CD33+) acute myeloid leukemia (AML), and adults and pediatric patients with CD33+ relapsed/refractory (R/R) AML.Objective: The aim of this study was to estimate the budgetary impact of introducing GO to a 1-million-member US health plan over a 5-year period.Methods: We developed models to estimate the impact of introducing GO in combination with conventional induction chemotherapy or as monotherapy for newly diagnosed AML, and as monotherapy for R/R AML. Models were built using data on drug costs and treatment-related outcomes obtained from published clinical trials and other publicly available sources. Results were reported on a per member/per year and per member/per month (PMPM) basis.Results: Base-case results of the newly diagnosed model indicated that the addition of GO in the combination setting reduced the overall budget of a 1-million-member health plan. The estimated net cost (US$) savings ranged from $72,969 ($0.006 PMPM) in year 1 to $745,426 ($0.062 PMPM) in year 5. In the monotherapy setting, GO was associated with increased net costs ranging from $4118 (0.0003 PMPM) in year 1 to $31,885 ($0.003 PMPM) in year 5. Base-case results of the R/R AML model demonstrated increased net costs that ranged from $17,326 ($0.001 PMPM) in year 1 to $46,163 ($0.004 PMPM) in year 5. Scenario analyses in all settings indicated the budget impact was not overly sensitive to the selected input assumptions, with the exception of the scenario considering only the pharmacy budget impact in the combination setting.Conclusions: The introduction of GO for newly diagnosed and R/R AML would have a minimal impact on the budget of a US health plan and could result in cost savings in the combination therapy setting for newly diagnosed AML. [ABSTRACT FROM AUTHOR]

Background: Health-related quality of life (HRQOL) in patients with chronic-phase chronic myeloid leukemia (CML) is important because of the requirement for long-term treatment. This study assessed HRQOL in bosutinib-treated patients with Philadelphia chromosome-positive CML and resistance or intolerance to 1 (chronic-phase second-line [CP2L]) or more (chronic-phase third-line [CP3L]) tyrosine kinase inhibitors who had 264 weeks or more of follow-up (ClinicalTrials.gov identifier NCT00261846).Methods: Patient-reported HRQOL was assessed with the EuroQol 5-Dimensions Questionnaire (EQ-5D) and the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu).Results: In total, 284 and 119 patients composed the CP2L and CP3L cohorts, respectively. At treatment completion, more than 50% of the patients in the CP2L and CP3L cohorts completed the EQ-5D and FACT-Leu assessments. The EQ-5D and EQ-5D visual analog scale scores were stable in both cohorts throughout treatment. The mean FACT-Leu scores were generally stable over time but were lower in magnitude in the CP3L cohort versus the CP2L cohort. The FACT-Leu scale scores of a subset of patients with chronic diarrhea (CP2L, n = 101; CP3L, n = 30) were similar to the scores of the larger cohorts. Minimally important differences (MIDs) from baseline for the FACT-Leu scale scores were observed for the following: emotional well-being (EWB), Functional Assessment of Cancer Therapy-General (FACT-G) Total, FACT-Leu Total, and Functional Assessment of Cancer Therapy Trial Outcome Index (FACT-TOI) in the CP2L cohort and FACT-Leu Total in the CP3L cohort. Among patients with chronic diarrhea, MIDs were observed for EWB, FACT-G Total, FACT-Leu Total, and FACT-TOI in the CP2L cohort and for EWB, FACT-G Total, and FACT-Leu Total in the CP3L cohort.Conclusions: HRQOL was maintained with long-term bosutinib treatment for patients with CP2L and CP3L CML. Cancer 2018;124:587-95. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. [ABSTRACT FROM AUTHOR]

Objective: Tofacitinib is a novel, oral Janus kinase inhibitor being investigated for psoriasis. This study assessed the relationship between pruritus and clinical signs of psoriasis (assessed by Physician's Global Assessment [PGA]) in patients with moderate-to-severe chronic plaque psoriasis receiving tofacitinib. Methods: In this 16-week (12-week treatment period, 4-week observation period), double-blind, placebo-controlled, phase IIb study (NCT00678210), 197 patients were randomized to tofacitinib 2, 5 or 15 mg BID, or placebo. Pruritus was patient assessed using the Itch Severity Score (ISS), a 0-10 (10 = worst itching) rating scale recorded daily from baseline to week 2 and at study visits. Mediation modeling was used to determine relationships between ISS (average score weeks 2-12), PGA (average score weeks 2-12) and treatment groups. Results: Mediation analysis showed that 70.2-80.5% ( p < 0.001 versus placebo) of tofacitinib's effect on pruritus was direct, and mostly independent of improvements in erythema, induration and scaling. ISS measurements had acceptable test-retest reliability. Correlation analyses with clinical outcomes supported the validity of the ISS as a pruritus measure. Conclusions: Tofacitinib has a direct, beneficial effect on patient-reported pruritus independent from improvements in clinician-reported psoriasis severity signs. The ISS demonstrated favorable psychometric characteristics, supporting its use as a pruritus assessment tool. [ABSTRACT FROM AUTHOR]

The Itch Severity Score (ISS), a 0-10 numeric rating scale, was used to assess pruritus due to psoriasis in a Phase 2 b trial of tofacitinib, a novel oral Janus kinase inhibitor. 197 patients with moderate-to-severe plaque psoriasis were randomized to tofacitinib 2, 5 or 15 mg twice daily, or placebo. The ISS was recorded daily from baseline to week 2 and at study visits. Following good and recommended research practice, we performed analyses to examine the clinically important differences (CID) (between-group difference or within-group difference) and clinically important responders (CIR) (within-patient change) for the ISS. The CID and CIR were defined using Patient Global Assessment of psoriasis as an anchor and were estimated with a longitudinal model. A CID on the ISS was 1.64 and, by day 10, the mean changes from baseline in ISS values for the tofacitinib doses (placebo-adjusted) exceeded CID. A CIR on the ISS was a 30% improvement from baseline and, at week 12, 87.2% to 100% of patients receiving tofacitinib reached ≥30% improvement versus 29.4% of patients receiving placebo ( p < 0.0001). Overall, the CID and CIR analyses play vital roles in the interpretation of the treatment effects measured by ISS. [ABSTRACT FROM AUTHOR]

Abstract: Previous research in our laboratory has examined the distribution of preferred hand (PH) reaches in working space with right-handed participants. In one study, we examined the effects of tool position and task demands on the frequency of PH reaches with right-handers (). We found that PH reaches were at a maximum within ipsilateral space, and predominated within contralateral space. This was mediated by the task demands, as shown by an increased frequency of PH reaches for the more skill demanding tasks. In the current study, we tested left-handed participants on the same procedure. Five different tools were placed in an array in front of the participant, who was required to reach for, and perform one of three tasks with the tool: Lift the tool; lift and Pantomime its use; or lift and Use the tool on its corresponding object. The results showed that PH reaches were at a maximum within ipsilateral space for all three tasks. Significantly fewer PH reaches were made for tools in contralateral space. In particular, almost no PH reaches were made for the Lift task at the most extreme contralateral position. This indicates the willingness of left-handers to use their non-preferred (i.e., right) hand. One possible explanation supported by these results is that left-handers have adapted to an environment designed for right-handers. [Copyright &y& Elsevier]

Performance-based measures of hand preference have been developed as an objective method of examining handedness. Previous research using this method by showed that both skill demands and the position of the object in working space affect preferential hand reaching. Specifically, preferred hand reaches predominated in left hemispace, in spite of the biomechanical inefficiency involved in reaching across the body midline. This was mediated by the skill demands, with a higher frequency of preferred hand reaches for tasks requiring more skill. To further examine this issue, we increased the task skill demands. Twenty-two right-handed adults reached for five tools located in an array of five positions in front of them. Participants were required to pick up the tool, pick up and demonstrate how to use it, or pick up and actually use the tool on the materials provided. The results showed that the frequency of right hand reaches was greatest for the tool use condition. This effect was mediated by the position of the object in hemispace, with more right hand reaches occurring for the Use task in left hemispace than the other tasks, in support of our previous work (). [Copyright &y& Elsevier]

Objective: In clinical trials of second-line therapies for chronic phase chronic myeloid leukemia (CP-CML), to date, only single-arm trials have been conducted for the available tyrosine kinase inhibitor treatments (bosutinib, dasatinib and nilotinib). These trials included heterogeneous patient populations in terms of disease and baseline characteristics. These hamper the use of standard network meta-analyses for indirect treatment comparison of relative efficacy. In this situation, a matching-adjusted indirect comparison (MAIC) in second-line CP-CML was performed. The aim was to compare the relative efficacies of bosutinib, dasatinib and nilotinib in second-line CP-CML patients.Methods: The MAIC was preceded by a systematic literature review that ensured inclusion of the underlying data for the analyses. The outcomes were measured in terms of overall survival (OS), progression-free survival (PFS) and major cytogenetic response (MCyR). The treatments were quantitatively compared based on Cox proportional hazard ratio (HR) regressions, on restricted mean survival (RMST, when the proportionality assumption showed evidence of violation) and on odds ratios (for response measures).Results: Comparing with dasatinib, bosutinib resulted in HRs for PFS and OS of 0.63 (0.44-0.90, p < .05) and 0.82 (0.54-1.26, p = .37) respectively, and resulted in an OR for MCyR of 0.78 (0.53-1.16). Although the proportionality of hazards assumption was violated for PFS, the RMST analyses confirmed the findings of the Cox regression. When compared with nilotinib, bosutinib showed a significant HR of 0.54 (0.38-0.76, p < .01) in favor of bosutinib for PFS, a non-significant HR of 0.72 (0.46-1.13, p = .16) for OS and a non-significant OR of 0.98 (0.71-1.35) for MCyR.Conclusions: Bosutinib had a significantly greater PFS than both dasatinib and nilotinib. For OS, the findings were numerically in favor of bosutinib, but not statistically significant. For MCyR, the findings were numerically in favor of dasatinib and nilotinib, but not statistically significant. [ABSTRACT FROM AUTHOR]

Estimates of direct and indirect costs of psoriasis are limited. The aim of this study was to estimate: (i) costs in patients with psoriasis compared with controls; and (ii) impact on costs from initiating biologics. The study extracted data from Swedish administrative registers and compared 31,043 patients with 111,645 sex-, age- and residency-matched referents. Mean direct and indirect costs were estimated as US dollars (USD) 1,365 (62%) and USD 3,319 (50%) higher in patients compared with referents, respectively. The study included 352 patients treated with biologics who had at least 1-year follow-up before and after initiation of biologics. Among the 193 patients persistent with biologics for one year, 1-year costs of biologics were estimated at USD 23,293 (95% confidence interval (95% CI) 22,372-24,199). This cost was partially offset, with savings in direct costs estimated to range from USD -1,135 (95% CI -2,050 to -328) to USD -4,422 (95% CI -6,552 to -2,771), depending on assumptions. The corresponding estimates for indirect costs savings were from USD -774 (95% CI -2,019-535) to USD -1,875 (95% CI -3,650 to -188). The study suggests that psoriasis is associated with substantial costs, which may be modifiable with treatment. [ABSTRACT FROM AUTHOR]

Several studies have shown excess risk for a number of comorbidities in patients with psoriasis compared with the general population, but data on cause-specific mortality in this patient population are limited. The aim of this study was to estimate the associations of psoriasis and 12 specific causes of death and all-cause mortality in patients with mild and severe psoriasis. The study was based on data from Swedish administrative registers and compared the risk of death in 39,074 patients with psoriasis with 154,775 sex-, age- and residency-matched referents using Cox proportional hazards models. In patients with mild and severe psoriasis, the strongest associations were observed for deaths due to kidney disease (hazard ratio [HR]=2.20, p < 0.01) and liver disease (HR = 4.26, p < 0.001), respectively. Whilst cardiovascular disease was the main driver of excess mortality in absolute terms, the risks for other causes of death were also substantially elevated in patients with psoriasis compared with matched referents. [ABSTRACT FROM AUTHOR]

Background and Objective: The phase III ALFA-0701 study demonstrated the efficacy and safety of gemtuzumab ozogamicin (GO) versus standard of care (SOC) chemotherapy (daunorubicin and cytarabine) for the treatment of adult patients with de novo CD33+ acute myeloid leukaemia (AML). This study analysed the cost-effectiveness of GO from the perspective of the UK health care payer.A cohort state-transition model was developed to estimate direct health care costs and quality-adjusted life-years (QALYs) over a lifetime time horizon from AML diagnosis to death using monthly cycles. Data on complete remission, overall survival, relapse-free survival (RFS), haematopoietic stem-cell transplantation, and adverse events for GO plus SOC versus SOC were obtained from the ALFA-0701 study. Overall survival and RFS were extrapolated beyond the trial horizon using mixture cure models. Unit costs were obtained from standard national sources. Utilities were identified in a systematic literature review. Costs and outcomes were discounted at 3.5%. Analyses were performed for the base-case population, excluding patients with an unfavourable cytogenetic profile, and the overall population.For the base-case and overall populations respectively, incremental per-patient costs (£13,456 and £14,773) and QALYs (0.99 and 0.68) for GO plus SOC versus SOC resulted in incremental cost-effectiveness ratios (ICERs) of £13,561 and £21,819 per QALY gained. The mean probabilistic ICERs were £14,217 and £23,245, respectively. Univariate sensitivity analyses supported the robustness of the results.The ICERs for both populations met NICE’s £20,000–£30,000 willingness-to-pay threshold for medicines and supported the current approval for GO.Methods: The phase III ALFA-0701 study demonstrated the efficacy and safety of gemtuzumab ozogamicin (GO) versus standard of care (SOC) chemotherapy (daunorubicin and cytarabine) for the treatment of adult patients with de novo CD33+ acute myeloid leukaemia (AML). This study analysed the cost-effectiveness of GO from the perspective of the UK health care payer.A cohort state-transition model was developed to estimate direct health care costs and quality-adjusted life-years (QALYs) over a lifetime time horizon from AML diagnosis to death using monthly cycles. Data on complete remission, overall survival, relapse-free survival (RFS), haematopoietic stem-cell transplantation, and adverse events for GO plus SOC versus SOC were obtained from the ALFA-0701 study. Overall survival and RFS were extrapolated beyond the trial horizon using mixture cure models. Unit costs were obtained from standard national sources. Utilities were identified in a systematic literature review. Costs and outcomes were discounted at 3.5%. Analyses were performed for the base-case population, excluding patients with an unfavourable cytogenetic profile, and the overall population.For the base-case and overall populations respectively, incremental per-patient costs (£13,456 and £14,773) and QALYs (0.99 and 0.68) for GO plus SOC versus SOC resulted in incremental cost-effectiveness ratios (ICERs) of £13,561 and £21,819 per QALY gained. The mean probabilistic ICERs were £14,217 and £23,245, respectively. Univariate sensitivity analyses supported the robustness of the results.The ICERs for both populations met NICE’s £20,000–£30,000 willingness-to-pay threshold for medicines and supported the current approval for GO.Results: The phase III ALFA-0701 study demonstrated the efficacy and safety of gemtuzumab ozogamicin (GO) versus standard of care (SOC) chemotherapy (daunorubicin and cytarabine) for the treatment of adult patients with de novo CD33+ acute myeloid leukaemia (AML). This study analysed the cost-effectiveness of GO from the perspective of the UK health care payer.A cohort state-transition model was developed to estimate direct health care costs and quality-adjusted life-years (QALYs) over a lifetime time horizon from AML diagnosis to death using monthly cycles. Data on complete remission, overall survival, relapse-free survival (RFS), haematopoietic stem-cell transplantation, and adverse events for GO plus SOC versus SOC were obtained from the ALFA-0701 study. Overall survival and RFS were extrapolated beyond the trial horizon using mixture cure models. Unit costs were obtained from standard national sources. Utilities were identified in a systematic literature review. Costs and outcomes were discounted at 3.5%. Analyses were performed for the base-case population, excluding patients with an unfavourable cytogenetic profile, and the overall population.For the base-case and overall populations respectively, incremental per-patient costs (£13,456 and £14,773) and QALYs (0.99 and 0.68) for GO plus SOC versus SOC resulted in incremental cost-effectiveness ratios (ICERs) of £13,561 and £21,819 per QALY gained. The mean probabilistic ICERs were £14,217 and £23,245, respectively. Univariate sensitivity analyses supported the robustness of the results.The ICERs for both populations met NICE’s £20,000–£30,000 willingness-to-pay threshold for medicines and supported the current approval for GO.Conclusions: The phase III ALFA-0701 study demonstrated the efficacy and safety of gemtuzumab ozogamicin (GO) versus standard of care (SOC) chemotherapy (daunorubicin and cytarabine) for the treatment of adult patients with de novo CD33+ acute myeloid leukaemia (AML). This study analysed the cost-effectiveness of GO from the perspective of the UK health care payer.A cohort state-transition model was developed to estimate direct health care costs and quality-adjusted life-years (QALYs) over a lifetime time horizon from AML diagnosis to death using monthly cycles. Data on complete remission, overall survival, relapse-free survival (RFS), haematopoietic stem-cell transplantation, and adverse events for GO plus SOC versus SOC were obtained from the ALFA-0701 study. Overall survival and RFS were extrapolated beyond the trial horizon using mixture cure models. Unit costs were obtained from standard national sources. Utilities were identified in a systematic literature review. Costs and outcomes were discounted at 3.5%. Analyses were performed for the base-case population, excluding patients with an unfavourable cytogenetic profile, and the overall population.For the base-case and overall populations respectively, incremental per-patient costs (£13,456 and £14,773) and QALYs (0.99 and 0.68) for GO plus SOC versus SOC resulted in incremental cost-effectiveness ratios (ICERs) of £13,561 and £21,819 per QALY gained. The mean probabilistic ICERs were £14,217 and £23,245, respectively. Univariate sensitivity analyses supported the robustness of the results.The ICERs for both populations met NICE’s £20,000–£30,000 willingness-to-pay threshold for medicines and supported the current approval for GO. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: In the phase 3 BFORE trial (NCT02130557), treatment with bosutinib resulted in a significantly higher major molecular response rate at 12 months versus imatinib in the modified intent-to-treat (mITT) population of patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML). Assessment of patient-reported outcomes (PROs) was an exploratory objective. Methods: Patients with newly diagnosed CP CML were randomized 1:1 to receive once-daily bosutinib 400 mg or imatinib 400 mg as first-line therapy. Patients completed the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) and EuroQoL-5 Dimensions (EQ-5D) questionnaires at baseline, every 3 months for the first 24 months of treatment, every 6 months thereafter, and at treatment completion. We report PRO results at month 12 in the mITT population (bosutinib: n = 246; imatinib: n = 241). Results: Mean FACT-Leu combined and subscale scores were similar at baseline in the bosutinib and imatinib arms; at month 12, all scores demonstrated improvement or maintenance of health-related quality of life (HRQoL) in both treatment arms. Repeated-measures mixed-effects models showed no significant difference between bosutinib and imatinib for any FACT-Leu score. Functional health status, as measured by EQ-5D, also demonstrated improvement or maintenance with bosutinib and imatinib at month 12. Conclusions: Similar improvements in PROs compared with baseline were seen after 12 months of treatment with first-line bosutinib or imatinib in the BFORE trial. Newly diagnosed patients with CP CML receiving bosutinib or imatinib can preserve or improve HRQoL during treatment, although clinical efficacy was superior with bosutinib. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Psoriasis patients frequently switch among multiple therapies while managing their psoriasis. Determining treatment transitions is fundamental to understanding how patients access and use treatments. Objective: We aimed to identify patterns of treatment transitions of US patients with moderate to severe psoriasis over 5 years. Methods: This was a retrospective, longitudinal cohort study in which US patients aged ≥18 years who had at least one psoriasis claim (International Classification of Diseases, Ninth Revision [ICD-9] diagnosis) were continuously enrolled in a health plan between October 2007 and September 2012. Data from eligible patients were projected to reflect the total US insured population with moderate to severe psoriasis, and the proportions of patients who started, stopped, switched, and restarted treatment at any time between September 2011 and September 2012 were analyzed. Treatment categories were biologics, traditional oral systemics, topicals, phototherapy, lapsed from treatment, and treatment-naive. Results: There were 8.9 million patients in the claims database, of whom 0.9 million (10.4%) had a psoriasis diagnosis and 46,369 (0.5%) met the inclusion criteria. When projected, 1.7 million insured patients had moderate to severe psoriasis. Of these, an estimated 807,000 patients had lapsed treatment, an additional 346,000 were receiving treatment, and 547,000 were defined as being treatment-naive. A total of 81,000 of 346,000 patients had switched treatment in the preceding year. In addition, many patients stopped (438,000) and restarted (384,000) treatment in the 12-month period. Conclusion: Based on health claims data, undertreatment of moderate to severe psoriasis appeared to be common. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis is a chronic inflammatory disorder with significant morbidity and mortality, but a persistent gap appears to exist for the adequate treatment of patients with moderate to severe disease. As the extent of under-treatment is unknown, we attempted to determine overall treatment patterns and estimate under-treatment using a large database. Methods: Data from the US National Health and Wellness Survey was used to estimate the proportion of patients with mild, moderate or severe psoriasis. The proportion with moderate to severe disease was estimated by excluding those with mild disease, and projecting this to the total insured US population, weighted by age and gender. Using US health plan claims data, patient totals by treatment type were determined between October 1, 2007 and September 30, 2012. Patients had to be continuously enrolled in a health plan and be ≥18 years at the end of the analysis window. Psoriasis was confirmed if patients had at least one claim of any type of psoriasis except psoriatic arthropathy (ICD-9 code 696.1). A monthly treatment history, classified by biologic, traditional oral systemic, phototherapy and topical therapy, was recorded for each patient. Results: There were an estimated 1.7 million insured US patients with moderate to severe psoriasis. Of these, 1 million (59%) were not treated for their condition in the preceding year. Among 695,488 patients who were treated for psoriasis in the preceding year, 346,201 were currently receiving treatment and 349,287 had lapsed treatment. Of the patients lapsed and currently treated in this period, the numbers who received each treatment type were 156,409 (biologic), 222,657 (traditional oral systemic), 22,911 (phototherapy), and 293,511 (topical). A limitation of the study was that only insurance claims were analyzed. Conclusion: Moderate to severe psoriasis remains persistently untreated or under-treated. We suggest that potential barriers preventing access to care be explored. Funding: This study was sponsored by Pfizer Inc. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Background: Health state (HS) utility values for patients with acute myeloid leukemia (AML), a hematological malignancy, are not available in the United Kingdom (UK). This study aims to develop clinically sound HSs for previously untreated patients with AML and to assign utility values based on preferences of the general UK population.Methods: This study was conducted in the UK and comprised 2 stages. During the first stage, AML HSs were drafted based on evidence from a literature review of AML clinical and health-related quality-of-life studies (published January 2000-June 2016) and patient-reported outcome measures previously used in this population. A panel of UK hematologists with AML experience validated the clinical relevance and accuracy of the HSs. During the second stage, validated HSs were valued in an elicitation survey with a representative UK population sample using the time trade-off (TTO) method. Descriptive statistics and bivariate tests were obtained and performed.Results: A total of eight HSs were developed and clinically validated, including treatment with chemotherapy, consolidation therapy, transplant, graft-vs-host disease (GvHD), remission, relapse, refractory, and functionally cured. In total, 125 adults participated (mean age, 49.6 years [range, 18-87 years], 52.8% female). Mean (95% confidence interval [CI]) TTO preference values (n = 120), ranked from lowest (worst HS) to highest (best HS) were as follows: refractory - 0.11 (- 0.21 to - 0.01), relapse 0.10 (0.00-0.20), transplant 0.28 (0.20-0.37), treatment with chemotherapy 0.36 (0.28-0.43), GvHD 0.43 (0.36-0.50), consolidation 0.46 (0.40-0.53), remission 0.62 (0.57-0.67), and functionally cured 0.76 (0.72-0.79). Mean (95% CI) visual analog scale preference values followed the same rank order, ranging from 0.15 (0.13-0.17) for refractory to 0.71 (0.68-0.73) for functionally cured.Conclusions: To our knowledge, this is the first study to report utility values for AML from the UK societal perspective. Participants were able to distinguish differences in severity among AML HSs, and preference values were consistent with clinical perception of HS severity. HS preference values observed in this study may be useful in future evaluations of treatment benefit, including cost-effectiveness analyses and improved patient well-being. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]