Background In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton’s tyrosine kinase, in patients at risk for a poor outcome. Methods In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points. Results At a median follow-up of 9.4 months, ibrutinib significantly improved progression-free survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall survival (hazard ratio for death, 0.43; P = 0.005). At 12 months, the overall survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues. The most frequent nonhematologic adverse events were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue, infusion-related reactions, and cough in the ofatumumab group. Conclusions Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL. (Funded by Pharmacyclics and Janssen; RESONATE ClinicalTrials.gov number, NCT01578707.)

Key Points Our 5-year experience shows sustained single-agent efficacy of ibrutinib in CLL patients, with complete response rates increasing over time. Long-term ibrutinib was well tolerated with no new safety signals; rates of grade ≥3 cytopenias decreased with continued therapy.

No abstract

No abstract

No abstract

IMPORTANCE Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease with an unmet need for treatments that provide rapid and high levels of skin clearance and itch improvement.OBJECTIVE To assess the safety and efficacy of upadacitinib vs dupilumab in adults with moderate-to-severe AD.DESIGN, SETTING, AND PARTICIPANTS Heads Up was a 24-week, head-to-head, phase 3b, multicenter, randomized, double-blinded, double-dummy, active-controlled clinical trial comparing the safety and efficacy of upadacitinib with dupilumab among 692 adults with moderate-to-severe AD who were candidates for systemic therapy. The study was conducted from February 21, 2019, to December 9, 2020, at 129 centers located in 22 countries across Europe, North and South America, Oceania, and the Asia-Pacific region. Efficacy analyses were conducted in the intent-to-treat population.INTERVENTIONS Patients were randomized 1:1 and treated with oral upadacitinib, 30 mg once daily, or subcutaneous dupilumab, 300 mg every other week. MAIN OUTCOMES AND MEASURESThe primary end point was achievement of 75% improvement in the Eczema Area and Severity Index (EASI75) at week 16. Secondary end points were percentage change from baseline in the Worst Pruritus Numerical Rating Scale (NRS) (weekly average), proportion of patients achieving EASI100 and EASI90 at week 16, percentage change from baseline in Worst Pruritus NRS at week 4, proportion of patients achieving EASI75 at week 2, percentage change from baseline in Worst Pruritus NRS (weekly average) at week 1, and Worst Pruritus NRS (weekly average) improvement of 4 points or more at week 16. End points at week 24 included EASI75, EASI90, EASI100, and improvement of 4 points or more in Worst Pruritus NRS from baseline (weekly average). Safety was assessed as treatment-emergent adverse events in all patients receiving 1 or more dose of either drug. RESULTSOf 924 patients screened, 348 (183 men [52.6%]; mean [SD] age, 36.6 [14.6] years) were randomized to receive upadacitinib and 344 were randomized to receive dupilumab (194 men [56.4%]; mean [SD] age, 36.9 [14.1] years); demographic and disease characteristics were balanced among treatment groups. At week 16, 247 patients receiving upadacitinib (71.0%) and 210 patients receiving dupilumab (61.1%) achieved EASI75 (P = .006). All ranked secondary end points also demonstrated the superiority of upadacitinib vs dupilumab, including improvement in Worst Pruritus NRS as early as week 1 (mean [SE], 31.4% [1.7%] vs 8.8% [1.8%]; P < .001), achievement of EASI75 as early as week 2 (152 [43.7%] vs 60 [17.4%]; P < .001), and achievement of EASI100 at week 16 (97 [27.9%] vs 26 [7.6%]; P < .001). Rates of serious infection, eczema herpeticum, herpes zoster, and laboratory-related adverse events were higher for patients who received upadacitinib, whereas rates of conjunctivitis and injection-site reactions were higher for patients who received dupilumab.CONCLUSIONS AND RELEVANCE During 16 weeks of treatment, upadacitinib demonstrated superior efficacy vs dup...

февраля 2021 года ЯрославльУчастники: • Насонов Евгений Львович -академик РАН, д. м.н., профессор, Заслуженный деятель науки РФ, президент Общероссийской общественной организации «Ассоциация ревматологов России», главный внештатный специалист-ревматолог Минздрава России. • Мазуров Вадим Иванович -академик РАН, д. м.н., профессор, Заслуженный деятель науки РФ, Первый вице-президент Общероссийской общественной организации «Ассоциация ревматологов России», главный специалист-ревматолог Северо-Западного федерального округа и г. Санкт-Петербурга, директор НИИ ревматологии ФГБОУ ВО «Северо-Западный государственный медицинский университет им. И. И. Мечникова» Минздрава России. • Лила Александр Михайлович -д. м.н., профессор, директор ФГБНУ «Научно-исследовательский институт ревматологии им. В. А. Насоновой». • Дубинина Татьяна Васильевна -к. м.н., и. о. генерального секретаря Общероссийской общественной организации «Ассоциация ревматологов России», главный внештатный специалист (Центральный федеральный округ), секретарь профильной комиссии, заведующая лабораторией медикосоциальных проблем ревматологии ФГБНУ «Научноисследовательский институт ревматологии им. В. А. Насоновой». • Коротаева Татьяна Викторовна -д. м.н., заведующая лабораторией спондилоартритов и спориатического артрита ФГБНУ «Научно-исследовательский институт ревматологии им. В. А. Насоновой». • Лапшина Светлана Анатольевна -к. м.н., доцент кафедры госпитальной терапии ФГБОУ ВО «Казанский государственный медицинский университет» Минздрава России. • Гайдукова Инна Зурабиевна -д. м.н., профессор кафедры терапии, ревматологии, экспертизы временной нетрудоспособности и качества медицинской помощи

NCT01162681.