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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]

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]

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]