Serum markers associated with clinical improvement in patients with ankylosing spondylitis treated with golimumab

Abstract

ObjectiveIdentify serum biomarkers modulated by golimumab treatment and associated with clinical response in patients with ankylosing spondylitis (AS).MethodsSera were collected at weeks 0, 4 and 14 from 100 patients with active AS in the GO–RAISE study. Patients were randomly assigned subcutaneous injections of placebo, golimumab 50 mg, or golimumab 100 mg every 4 weeks. Samples were tested for select inflammatory, bone and cartilage markers, and protein profiling was also performed.ResultsGolimumab treatment resulted in significant decreases in several serum proteins at weeks 4 and 14 compared with placebo. Patients who achieved clinical response at week 14, as assessed by a ≥20% improvement in the Assessment in SpondyloArthitis international Society response criteria (ASAS 20), demonstrated a distinct biomarker profile with lower levels of acute phase reactants and inflammatory biomarkers compared with patients who did not. Notably, combinations of two or three biomarkers assessed at baseline were predictive of various clinical outcomes (ASAS 20, Bath ankylosing spondylitis disease activity index 50 or Bath ankylosing spondylitis functional index) using a logistic regression analysis, and the overall predictive values for these combined biomarkers were greater than observed for C-reactive protein (CRP) alone.ConclusionGolimumab modulated acute phase reactants and inflammatory markers in patients with active AS. Specific combinations of biomarkers at baseline demonstrated a stronger prediction for clinical efficacy than CRP alone. These data provide insights into the mechanism of golimumab on inflammatory processes driving AS pathology, and may have utility in managing the treatment of patients with AS.

Serum Vascular Endothelial Growth Factor Levels Lack Predictive Value in Patients with Active Ankylosing Spondylitis Treated with Golimumab

“…The lack of corroboration with findings of Poddubnyy, et al 13 , suggesting that VEGF is predictive of radiographic progression, is most likely explained by the major difference in treatment. In the GO-RAISE trial, all patients with AS had been treated with GOL, known to strongly suppress VEGF levels 19 , whereas about 3% of the German Spondyloarthritis Inception Cohort (GESPIC) patients, a large proportion of whom had axial spondyloarthritis, had been exposed to TNF antagonists 13 .…”

“…Serum samples collected at weeks 0, 4, 14, 24, and 104 of the GO-RAISE trial were tested for selected markers using an ELISA platform by Quintiles Laboratories 19 .…”

Efficacy of golimumab in the treatment of patients with ankylosing spondylitis (according to the data of a long-term follow-up)

“…В более ранних работах было показано, что повышение концентрации ФНО, межклеточных молекул адгезии 1 (ICAM1), фактора роста эндотелия сосудов (VEGF) в сыворотке больных АС коррелирует с уровнем СРБ и активностью заболевания, а увеличение уровня матриксной металлопротеиназы (ММР) 3 может рассматриваться как независимый предиктор струк-турных повреждений [8].…”

“…Исходный уровень тканевого ингибитора ММП1 и P1NP лучше прогнозирует ответ функционального улучшения, оцениваемого по индексу BASFI (Bath Ankylosing Spondylitis Functional Index) [4,8].…”

Role of laboratory biomarkers in monitoring and prediction of the effectiveness of treatment of rheumatic diseases using genetically engineered drugs

“…У больных АС хороший ответ на ГЛМ по ASAS20 через 14 нед терапии сопровождался снижением базального уров-ня P1NP, остеокальцина, инсулина, фактора Виллебранда, лептина и аполипопротеина С3, а также концентрации дан-ных показателей, С3-компонента комплемента, СРБ, сыво-роточного амилоидного белка Р, ИЛ6 и повышением уровня гаптоглобина и воспалительного маркера ENA78 на 4-й и 14-й неделе применения ГЛМ [24]. В той же работе показа-но, что комбинация базальных уровней 2 и более биомарке-ров (P1NP и инсулин; лептин, IgM и VEGF; TIMP1 и VEGF) позволяет более достоверно прогнозировать достижение от-вета на ГЛМ по критериям ASAS20, BASDAI50 и BASFI, чем исходная концентрация СРБ.…”