Serum IL-33, a new marker predicting response to rituximab in rheumatoid arthritis

Abstract

BackgroundRecent works have suggested a possible link between interleukin (IL)-33 and B-cell biology. We aimed to study the possible association between serum IL-33 detection and response to rituximab (RTX) in rheumatoid arthritis (RA) patients in different cohorts with an accurate enzyme-linked immunosorbent assay (ELISA).MethodsSerum IL-33, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and high serum immunoglobulin (Ig)G levels were assessed in 111 RA patients receiving a first course of 2 g RTX (cohort 1) in an observational study and in 74 RA patients treated with the same schedule in routine care (cohort 2). Univariate and multivariate analyses identified factors associated with a European League Against Rheumatism (EULAR) response at 24 weeks.ResultsAt week 24, 84/111 (76%) and 54/74 (73%) patients reached EULAR response in cohorts 1 and 2, respectively. Serum IL-33 was detectable in only 33.5% of the patients. In the combined cohorts, the presence of RF or anti-CCP (odds ratio (OR) 3.27, 95% confidence interval (CI) 1.13–9.46; p = 0.03), high serum IgG (OR 2.32, 95% CI 1.01–5.33; p = 0.048), and detectable serum IL-33 (OR 2.40, 95% CI 1.01–5.72; p = 0.047) were all associated with RTX response in multivariate analysis. The combination of these three factors increased the likelihood of response to RTX. When serum IL-33 detection was added to seropositivity and serum IgG level, 100% of the patients with the three risk factors (corresponding to 9% of the population) responded to RTX (OR versus patients with none of the three risk factors 29.61, 95% CI 1.30–674.79; p = 0.034).ConclusionDetectable serum IL-33 may predict clinical response to RTX independently of, and synergistically with, auto-antibodies and serum IgG level.Trial registration NCT01126541; 18 May 2010.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1190-z) contains supplementary material, which is available to authorized users.

Using the Immunophenotype to Predict Response to Biologic Drugs in Rheumatoid Arthritis

“…IL-33 is a Th2 polarizing cytokine and, when detected and added to ACPA status and serum IgG level, predicted 100 % of rituximab responders with an OR of almost 30 in one study [39], although this work is yet to be validated in an independent cohort.…”

Cytokines in the pathogenesis of rheumatoid arthritis: new players and therapeutic targets

“…Secondly, RA patients with lower sST2 levels at baseline are those who more likely achieved remission following 12 months of treatment with disease modifying anti-rheumatic drugs (DMARDs) and anti-TNF-α agents [30]. Finally, baseline detectable serum IL-33 levels have been associate to a good clinical response to rituximab [31]. Interestingly, baseline IL-33 and sST2 levels have been also associated to cardiovascular risk factors.…”

The Role of Laboratory Biomarkers in Predicting the Efficiency of Rituximab Therapy for Rheumatoid Arthritis: New Evidence

“…В недавнем исследовании французских ученых была продемонстрирована роль ИЛ33 в сочетании с другими биомаркерами для прогнозирования эффективности тера-пии РТМ при РА [38].…”

“…Для оценки сывороточного уровня ИЛ33 X. Mariette и соавт. [38] использовали метод иммуноферментного ана-лиза. В исследование было включено 111 пациентов из ко-горты исследования SMART (1-я группа), а также 32 паци-ента из Великобритании и 42 больных из Франции (эти па-циенты составили 2-ю группу -реальной клинической практики).…”