Long-term outcomes of peginterferon beta-1a in multiple sclerosis: results from the ADVANCE extension study, ATTAIN

Abstract

Background:ADVANCE was a phase III trial of the efficacy and safety of subcutaneous peginterferon beta-1a 125 µg every 2 or 4 weeks in patients with relapsing-remitting multiple sclerosis (RRMS). ATTAIN was a 2-year extension study of ADVANCE. The aim was to evaluate the long-term safety, tolerability, and efficacy of peginterferon beta-1a 125 µg every 2 or 4 weeks in ATTAIN.Methods:ADVANCE dosing schedules were maintained in ATTAIN, except that every-4-weeks dosing patients were switched to every-2-weeks dosing after conversion of the study to an open-label protocol. ATTAIN was considered complete when the last patient completed the 96-week extension study. Primary endpoints included adverse event (AE) and serious AE (SAE) incidence. Secondary endpoints included relapse, magnetic resonance imaging, and disability outcomes.Results:Of the 1512 patients randomized in ADVANCE, 1076 (71%) continued treatment in ATTAIN; of these, 842 (78%) completed the open-label extension study. During ATTAIN, 478 patients (87%) in the every-2-weeks group and 471 patients (89%) in the every-4-weeks group experienced an AE; SAEs were reported in 90 patients (16%) in the every-2-weeks group and 113 patients (21%) in the every-4-weeks group. The most frequent AEs reported were injection site reactions and flu-like symptoms, both of which numerically decreased over time. Peginterferon beta-1a every 2 weeks versus every 4 weeks significantly reduced the adjusted annualized relapse rate over 6 years (0.188 versus 0.263, p = 0.0052) and the risk of relapse over 5 years (36% versus 49%, p = 0.0018). Fewer new T1, new/newly enlarging T2, and gadolinium-enhancing magnetic resonance imaging lesions were observed with every-2-weeks dosing than every-4-weeks dosing over 4 years.Conclusions:Results from the ADVANCE extension study, ATTAIN, confirm the favorable long-term safety and tolerability profile of peginterferon beta-1a in patients with RRMS and provide additional evidence for the clinical and radiological benefits associated with this therapy.

Matching-adjusted comparisons demonstrate better clinical outcomes in patients with relapsing multiple sclerosis treated with peginterferon beta-1a than with teriflunomide

“…For this analysis, individual patient data of peginterferon beta-1a efficacy and safety from the randomized, double-blind, pivotal phase 3 study, ADVANCE (NCT00906399) (Kieseier et al, 2015), and its openlabel extension study, ATTAIN (NCT01332019) (Newsome et al, 2018), were compared with pooled aggregate teriflunomide efficacy and safety data from the randomized, double-blind, pivotal phase 3 studies TEMSO (O'Connor et al, 2011) (NCT00134563) and TOWER (Confavreux et al, 2014) (NCT00751881).…”

“…Patients in the ADVANCE/ATTAIN (Kieseier et al, 2015;Newsome et al, 2018) studies met a diagnosis of RRMS as defined by the 2005 McDonald criteria (Polman et al, 2005). In ADVANCE, patients were randomized 1:1:1 to receive subcutaneous (SC) injections of placebo, peginterferon beta-1a 125 mcg every 2 weeks, or peginterferon beta-1a 125 mcg every 4 weeks in year 1.…”

“…In order to help provide relevant information for clinicians on the comparative efficacy of peginterferon beta-1a and teriflunomide, we performed a matching-adjusted comparison (Signorovitch et al, 2012) of weighted individual data from patients receiving peginterferon beta-1a in the ADVANCE and ATTAIN clinical trials (Calabresi et al, 2014;Kieseier et al, 2015;Newsome et al, 2018) with pooled aggregate data from patients treated with teriflunomide in the TEMSO and TOWER clinical trials (Confavreux et al, 2014;O'Connor et al, 2011). A subset analysis of patients who were newly diagnosed with RMS (diagnosis ≤1 year before study enrollment and DMT naïve) was also performed.…”

The pegylated form of interferon beta in the treatment of multiple sclerosis

“…Клиническую эффективность ПЭГ-ИФН-β оценивали в крупном 2-летнем исследовании III фазы ADVANCE (1512 пациентов), и были получены доказательства 1-го класса позитивного влияния препарата на частоту обострений и прогрессирование инвалидизации при ремиттирующем РС [16]. Анализ долгосрочной безопасности и эффективности ПЭГ-ИФН-β проводили в расширении ADVANCE -исследовании ATTAIN (1076 пациентов) с максимальным сроком наблюдения пациентов в течение 6 лет [17]. В исследовании IIIb фазы ALLOW (194 пациентов) получены данные по безопасности переключения на ПЭГ-ИФН-β с других препаратов высокодозных ИФН-β [18].…”

“…При этом показана высокая приверженность пациентов лечению, так как число пациентов, отказавшихся от участия в исследовании из-за нежелательных явлений, составляло всего около 6% в каждой из исследуемых групп. Исследование ATTAIN изначально проводили как заслепленное по частоте введения ПЭГ-ИФН-β (каждые 2 или 4 нед) продолжение исследования ADVANCE [17]. Однако, учитывая результаты ADVANCE, продемонстрировавшие более высокую эффективность введения ПЭГ-ИФН-β каждые 2 нед, все пациенты, получавшие ПЭГ-ИФН-β каждые 4 нед, были переведены на 2-недельную схему приема.…”