Comparison of long‐term clinical outcome with etanercept treatment and adalimumab treatment of rheumatoid arthritis with respect to immunogenicity

Abstract

Objective. To compare rates of sustained low and minimal disease activity and remission according to the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria during 3-year followup in rheumatoid arthritis (RA) patients treated with etanercept and adalimumab in routine care.Methods. Four hundred seven RA patients previously unexposed to tumor necrosis factor antagonists were treated with etanercept (n ‫؍‬ 203) or adalimumab (n ‫؍‬ 204) and assessed at 3-and later 6-month intervals. Treatment allocation was at the discretion of the treating rheumatologist. Clinical parameters were measured at each time point, as were anti-adalimumab antibodies in adalimumab-treated patients. Achievement of clinical outcome was defined as the occurrence of sustained (at least 12 consecutive months) low disease activity (28-joint Disease Activity Score [DAS28] <3.2), minimal disease activity (DAS28 <2.6), or ACR/ EULAR remission based on the Simplified Disease Activity Index (SDAI). Non-overlapping response rates were calculated.Results. Among the adalimumab group, 13% reached sustained low disease activity but not sustained minimal disease activity, 15% reached sustained minimal disease activity but not sustained remission according to the SDAI, and 16% reached sustained ACR/ EULAR remission. In the etanercept group the corresponding rates were 16%, 11%, and 12%, respectively (P ‫؍‬ 0.42, overall test for linear trend). Adalimumabtreated patients without anti-adalimumab antibodies (n ‫؍‬ 150 [74%]) had the best outcomes, and adalimumab-treated patients with anti-adalimumab antibodies the worst, with outcomes in etanercepttreated patients in between (P < 0.0001). Differences were most apparent in the sustained SDAI remission and sustained minimal disease activity categories. For example, 40% of anti-adalimumab antibody-negative patients, 23% of etanercept-treated patients, and 4% of anti-adalimumab antibody-positive patients achieved at least sustained minimal disease activity.Conclusion. Overall, etanercept and adalimumab treatment appear similar in inducing a good long-term clinical outcome. However, in the case of adalimumab this is strongly dependent on the presence or absence of anti-adalimumab antibodies.

Candidate antirheumatic genotherapeutic plasmid constructions have low immunogenicity

“…На примере адалимумаба и эта нерцепта при лечении ревматоидного артрита пока-зано, что уровень таких антител обратно коррелирует с эффективностью терапии и уровнем биотерапевтических молекул в сыворотке пациентов (Krieckaert et al, 2012;Chen et al, 2015). Показано, что в присутствии специфи-ческих антител инфликсимаб слабо детектируется в сы-воротке пациентов (Eng et al, 2015).…”

“…В раз-личных лабораторных моделях показано, что реком-бинантный белок CrmB (47 кДа) можно использовать в качестве эффективного блокатора TNF (Гилева и др., 2006; Gileva et al, , 2015Цырендоржиев и др., 2013. Однако препараты для терапии заболеваний должны обладать низкой иммуногенностью, поскольку выявлено, что эффективность лечения может снижаться из-за развития иммунного ответа на терапевтический белок (Krieckaert et al, 2012;Bendtzen et al, 2015;Chen et al, 2015;Eng et al, 2015). Показано, что синтезированный в бактериальных клетках укороченный TNF-BD (17 кДа) эффективно связывается с человеческим TNF и обладает меньшей по сравнению с CrmB иммуногенностью при многократном введении лабораторным животным (Тре-губчак и др., 2015).…”

Combination Therapy of Etanercept and Fumarates versus Etanercept Monotherapy in Psoriasis: A Randomized Exploratory Study

“…Anti-etanercept antibodies have only sporadically been observed in clinical studies, indicating that loss of clinical efficacy for etanercept is probably caused by other, yet unidentified factors [25]. We argued that for improvement of the clinical efficacy of etancercept, inhibition of antidrug antibodies was less important, and that combination with oral fumarates could have an additive clinical effect.…”

Biosimilars: Clinical Interpretation and Implications for Drug Development

“…Minor changes in the molecular structure, including but not limited to protein sequence, aggregation, deamination, and glycosylation, may have a significant effect on drug performance and/or on the patient [20,21]. Loss of efficacy also is a frequent manifestation resulting from antibody production, and it has been reported with biologics [22].…”