Levels of interleukin-1 beta can predict response to tocilizumab therapy in rheumatoid arthritis: the PETITE (predictors of effectiveness of tocilizumab therapy) study

Abstract

Predicting the responses of patients with rheumatoid arthritis (RA) to tocilizumab is difficult, because inflammatory markers such as C-reactive protein rapidly normalize regardless of clinical efficacy. We aimed to identify factors that could predict response to tocilizumab. Sixty-five patients completed 52 weeks of tocilizumab therapy. Serum fibrinogen, D-dimer and interleukin (IL)-1β levels were measured at baseline and after 4 weeks of therapy. Clinical responses to tocilizumab were assessed using disease activity score 28-erythrocyte sedimentation rate and the clinical disease activity index at baseline and after 52 weeks of therapy (UMIN Clinical Trials Registry No. UMIN000002246). Mean age was 60.5 years (range 22-85 years). Mean disease duration was 11.2 years (range 0-45 years). All patients had moderate-to-severe disease activity and were resistant to disease-modifying anti-rheumatic drugs and/or other biologics. Baseline IL-1β levels were significantly lower in responders than in non-responders (p = 0.045), but multiple logistic regression analysis found no significant difference (adjusted odds ratio 2.74; 95 % confidence interval 0.84-8.95; p = 0.096). Low D-dimer and IL-1β levels at 4 weeks predicted greater decrease in disease activity after 52 weeks of treatment (p = 0.005 and p < 0.001, respectively). Effects of tocilizumab at 52 weeks could be predicted from D-dimer and IL-1β levels after 4 weeks of tocilizumab treatment. These markers might be more useful than current inflammatory markers for early-stage prediction of response to tocilizumab in RA.

Prediction of Response to Targeted Treatment in Rheumatoid Arthritis

“…77 Other relatively small studies suggested baseline serum IL-6 receptor levels as a predictor of clinical remission at week 24 78 and serum levels of IL-1b and D-dimer at 4 weeks after treatment as predictors of response at week 52. 79 High baseline natural killer cell numbers were also associated with remission after 3 months of tocilizumab therapy. 80 All these studies need to be confirmed in independent cohorts.…”

Systems model identifies baseline cytokine concentrations as potential predictors of rheumatoid arthritis inflammatory response to biologics

“…In practice, lower remission rates in rheumatoid arthritis patients receiving treatments including anti-TNFα biologics are significantly associated with obesity and greater body mass index (BMI) (Levitsky et al, 2017), which are related to higher serum IL-1β concentrations (Shoda et al, 2017). The PETITE study also demonstrated that rheumatoid arthritis patients with lower baseline IL-1β concentrations significantly responded to tocilizumab compared with those with higher values (Okano et al, 2016). Therapies targeting IL-1β have been shown to reduce disease activity in rheumatoid arthritis patients refractory to anti-TNFα therapy (Cavalli & Dinarello, 2015).…”

Predictive value of serum amyloid a levels for requirement of concomitant methotrexate in tocilizumab initiation: A post hoc analysis of the SURPRISE study

“…Several studies have so far aimed to predict the response to tocilizumab therapy in patients with RA. Although several predictive factors were identified [14][15][16][17][18][19], including serum levels of CRP, IL-6, soluble IL-6 receptor, soluble gp130, IL-1b, and osteopontin and platelet counts, most of the studies did not focus on the response to tocilizumab monotherapy, except one study by Kojima et al [20]. They analyzed the data from their registry and showed a positive association between concomitant use of methotrexate and remission achievement by tocilizumab therapy in patients with high baseline disease activity (DAS28-ESR > 5.1), which is compatible with our results showing DAS28-ESR at baseline as a predictive factor for remission achievement in SWITCH.…”