Long-term outcome of patients with active ankylosing spondylitis with etanercept-sustained efficacy and safety after seven years

Abstract

IntroductionData from clinical studies on the long-term efficacy and safety of anti-tumor necrosis factor (TNF)-α therapy in patients with ankylosing spondylitis (AS) are scarce. This is the first report on continuous treatment with the TNFα fusion protein etanercept over seven years (y).MethodsOverall, 26 patients with active AS were initially treated with etanercept 2 × 25 mg s.c./week with no concomitant disease modifying anti-rheumatic drugs (DMARDs) or steroids. The clinical response was assessed by standardized parameters. The primary outcome was the proportion of patients in the Spondyloarthritis International Society (ASAS) partial remission at seven years. AS disease activity scores (ASDAS) for status and improvement were compared to conventional outcome measures.ResultsOverall, 21/26 patients (81%) completed two years of treatment and 16/26 patients (62%) completed seven years. In the completer analysis, 31% patients were in ASAS partial remission at seven years, while 44% patients showed an ASDAS inactive disease status. Mean Bath AS activity index (BASDAI) scores, which were elevated at baseline (6.3 ± 0.9), showed constant improvement and remained low: 3.1 ± 2.5 at two years and 2.5 ± 2.2 at seven years, while ASDAS also improved (3.9 ± 0.7 at baseline, 1.8 ± 0.9 at two years, 1.6 ± 0.8 at seven years), all P <0.001. From the 10 dropouts, only 5 patients discontinued treatment due to adverse events. Patients who completed the study had lower baseline Bath AS function index (BASFI) scores vs. patients who discontinued. No other clinical parameter at baseline could predict any long-term outcome.ConclusionsThis study confirms the clinical efficacy and safety of etanercept in patients with active AS over seven years of continuous treatment. After seven years, more than half of the initially treated patients remained on anti-TNF therapy, and one-third were in partial remission.Trial RegistrationClinicalTrials.gov: NCT01289743

Cytokines as Therapeutic Targets in Rheumatoid Arthritis and Other Inflammatory Diseases

“…Tumor Necrosis Factor Inhibitor Withdrawal or Dose Reduction in Axial Spondyloarthritis. Long-term extension studies have shown sustained clinical efficacy of TNF inhibitors in patients who continue treatment (Baraliakos et al, 2011a(Baraliakos et al, , 2013a. A number of small and open-label extension studies have evaluated withdrawal of TNF inhibitors in AS and axSpA patients who are in remission.…”

Instrumented BASFI (iBASFI) Shows Promising Reliability and Validity in the Assessment of Activity Limitations in Axial Spondyloarthritis

“…For example, several longterm followup studies on anti-TNF now exist 45 and uniformly show a mean BASFI of about 7/10 at baseline which, after initial therapy response, remains stable at about 3/10 during the 8-year followup. In contrast, performance-based tests in AS may be more sensitive to change because they are able to detect improvement even in nonresponders 21 during anti-TNF therapy at 3 months of followup, although learning effects could not be excluded.…”

Clinical Experience With Etanercept in the Treatment of Patients With Ankylosing Spondylitis

“…В исследовании Х. Baraliakos и соавт. [3] был продемонстрирован устойчи-вый эффект длительного (>7 лет) применения ЭТЦ: ста-бильная эффективность по всем критериям улучшения АС была получена у 62% пациентов, частичная ремиссия по критериям ASAS -у 31,3% пациентов, низкая актив-ность по ASDAS -у 43,8% пациентов, сохранение BASDAI <3 и умеренной активности по ASDAS -у 68,8% пациентов. Полученные результаты свидетельствуют о высокой эффективности и хорошей переносимости препарата.…”

“…[2] было показано, что стойкий ответ по критери-ям Международного общества по оценке спондилоартри-тов (ASAS) на фоне терапии ЭТЦ сохранялся в течение 4 лет, причем частичная ремиссия наблюдалась у 44% паци-ентов, 40% улучшение по критериям ASAS и 50% сниже-ние BASDAI получено у 69% пациентов [2]. Одно из самых длительных наблюдений за эффективностью и переноси-мостью ЭТЦ у больных АС, начавшееся в 2005 г. в Герма-нии, продолжается свыше 10 лет, при этом более 7 лет те-рапию получали 62% больных (16 из 26), у трети из них со-хранялась клиническая ремиссия, у 44% -низкая актив-ность анкилозирующего спондилита (АС) [3]. ЭТЦ, в отли-чие от моноклональных антител (мАТ), стабильно снижает активность заболевания даже при возобновлении терапии после годичного перерыва [4], что может быть связано с более низкой, по сравнению с мАТ, выработкой антиней-трализующих антител [5].…”