SAT0233 Comparison of Abatacept and Other Biologic DMARDS for the Treatment of Rheumatoid Arthritis Patients: A Systematic Literature Review and Network Meta-Analysis: Table 1.

Abstract

Background Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that, if inadequately treated, often progresses to joint destruction. Currently, patients are initially treated with conventional disease- modifying anti-rheumatic drugs (DMARDs); in patients with an inadequate response (IR), biologic DMARDs are often combined with methotrexate (MTX) or other DMARDs to improve efficacy. Objectives To compare the relative efficacy and safety of abatacept versus all relevant biologic DMARDs in MTX-IR patients with RA. Methods A systematic literature review identified randomised controlled trials (RCTs) investigating the efficacy and safety of abatacept subcutaneous (sc) and intravenous (iv), adalimumab, certolizumab, etanercept, infliximab, golimumab, tocilizumab and tofacitinib, in combination with MTX. The efficacy endpoints were American College of Rheumatology (ACR) 20/50/70 response rates and disease activity score 28 joints (DAS28) remission rates (DAS28≤2.6). Safety endpoints were incidence of serious adverse events (AE), infections, and serious infections. Abatacept sc and iv were compared to tocilizumab and the combined group of anti-TNFs (adalimumab, certolizumab, etanercept, infliximab, golimumab). Results were analysed with Bayesian hierarchical network meta-analysis (NMA) models to estimate the relative efficacy and safety effects of the biologic DMARDs. Although tofacitinib RCTS were identified in the systematic literature search, they were not included in the NMA because the study population of the three tofacitinib RCTs was different than that of the other RCTs; the majority of the patients in the tofacitinib RCTs were previously exposed to biologic DMARDs, while the patients in the other RCTs were naive to biologic DMARDs. Results The search was performed in October 2013. A total of 21 RCTs were included. Results indicate that abatacept sc has similar ACR20/50/70 response rates and DAS28 remission rates compared to other biologic DMARDs after 24 weeks of treatment (Table 1). Similar efficacy results were found for abatacept iv (data not shown). Abatacept sc seems to have slightly better safety in comparison to tocilizumab and the combined anti-TNFs in terms of incidence of infections, serious infections, and serious AE (Table 1); however, none of these differences were statistically significant. Similar results were found when comparing abatacept iv with tocilizumab and the combined anti-TNFs (data not shown). Table 1. Odds ratios (OR) and 95% credible intervals Abatacept sc versus ACR 20 ACR 50 ACR 70 DAS28<2.6 No infection* No serious infection* No serious AE* Tocilizumab 1.12 (0.91; 1.49) 1.03 (0.86; 1.26) 0.98 (0.70; 1.22) 0.82 (0.28; 1.10) 0.96 (0.68; 1.20) 1.51 (0.76; 4.26) 1.11 (0.73; 1.83) Combined anti-TNFs 0.96 (0.78; 1.13) 1.01 (0.87; 1.17) 0.98 (0.79; 1.16) 0.94 (0.73; 1.13) 1.06 (0.88; 1.32) 1.54 (0.85; 3.79) 1.25 (0.89; 1.95) *Modelled as the odds of not having an infection, serious infection or serious AE. Conclusions Both abatacept sc and iv showed ...

2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty

“…This recommendation was based on evidence that was rated down in quality for indirectness, as no RCTs were performed in patients undergoing THA or TKA. We abstracted data from a systematic review of literature that included systematic reviews and meta‐analyses of biologic agents versus placebo (and occasionally versus control treatment including nonbiologic DMARDs) in nonsurgical patients, which revealed that the risk of serious infections was increased with biologic agents, with most odds/hazards/risk ratios ∼1.5 (range 0.61–8.87) and a higher risk of serious adverse events with most odds/hazards/risk ratios ∼1.5 (range 0.33–2.54) . Our systematic review did not provide ample evidence that would support a differential risk of serious infection among available biologic agents .…”

“…We abstracted data from a systematic review of literature that included systematic reviews and meta‐analyses of biologic agents versus placebo (and occasionally versus control treatment including nonbiologic DMARDs) in nonsurgical patients, which revealed that the risk of serious infections was increased with biologic agents, with most odds/hazards/risk ratios ∼1.5 (range 0.61–8.87) and a higher risk of serious adverse events with most odds/hazards/risk ratios ∼1.5 (range 0.33–2.54) . Our systematic review did not provide ample evidence that would support a differential risk of serious infection among available biologic agents . Because avoiding infection was significantly more important to patients than flares in the postoperative period, the Panel did not support separating biologic agents regarding infection risk in the perioperative period until further studies clarify and establish differences in risk .…”

Abatacept for Rheumatoid Arthritis: A Novel Formulation, New Mechanisms, New Possibilities

“…Иммуногенность под-кожной формы АБЦ не зависела от сопутствующего при-менения МТ и была сходной на фоне как монотерапии АБЦ подкожно (2%), так и комбинированной терапии АБЦ и МТ (3,9%) [27]. Завершая обсуждение основных результатов, касаю-щихся эффективности и безопасности подкожного введе-ния АБЦ при РА, следует обратить внимание на материалы недавно подготовленного систематического обзора и мета-анализа (сетевой) 21 РПКИ, посвященных сравнению эф-фективности и безопасности подкожной и внутривенной форм АБЦ и 5 ингибиторов ФНОα, моноклональных ан-тител к рецепторам ИЛ6 (тоцилизумаб -ТЦЗ), а также пе-рорального ингибитора JAK -тофацитиниба -в комбина-ции с МТ [38]. Установлено, что и подкожная, и внутри-венная формы АБЦ обладают сходной эффективностью, но безопасность (риск инфекционных осложнений, тяже-лых инфекций и тяжелых НР) был ниже на фоне подкож-ного введения АБЦ, чем других ГИБП (табл.…”

“…Сравнительная эффективность и безопасность подкожной формы АБЦ по сравнению с ингибиторами ФНОα и ТЦЗ, ОШ (95% ДИ) [38] CD4+ИЛ17A в периферической крови, что коррелирова-ло с положительной динамикой индекса DAS28, умень-шением концентрации ИЛ6 и ММП3. Принимая во вни-мание, что Т рег обладают способностью дифференциро-ваться в Th17-клетки, в том числе и при участии ИЛ6, а ИЛ17 (и ИЛ6) являются мощными индукторами RANKL на остеобластах (ОБ) и синовиальных фибробла-стах, эти результаты позволяют объяснить многоплано-вый механизм действия АБЦ на синовиальное воспале-ние и костную резорбцию при РА.…”

“…Например, в пользу назначения АБЦ при РА могут свидетельствовать клинические данные о его эф-фективности при синдроме Шегрена [189,190], который нередко сочетается с РА, особенно у АЦЦП-позитивных пациентов [191], при ревматоидном васкулите [192], бо-лезни Стилла взрослых [193,194], у пациентов с РА, име-ющих избыточную массу тела (в отличие от ингибиторов ФНОα) [195], а также с сахарным диабетом 1-го типа [196], риск развития которого повышен при РА. При вы-боре терапевтической тактики необходимо принимать во внимание, что АБЦ относится к числу наиболее «безо-пасных» ГИБП, особенно в отношении риска инфекци-онных осложнений [38,[197][198][199], реактивации латент-ной туберкулезной инфекции [200] и обострения интер-Л И Т Е Р А Т У Р А стициального заболевания легких (характерное систем-ное проявление РА) [201][202][203]. В этом отношении АБЦ может иметь преимущества перед другими ГИБП, в пер-вую очередь ингибиторами ФНОα.…”