title: 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.
authors.affiliation: Departments of Orthopaedic Surgery, Osaka City University Medical School, Osaka, 545-8585, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okano
authors.affiliation: Departments of Orthopaedic Surgery, Osaka City University Medical School, Osaka, 545-8585, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Inui
authors.affiliation: Departments of Orthopaedic Surgery, Osaka City University Medical School, Osaka, 545-8585, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tada
authors.affiliation: Center for Senile Degenerative Disorders, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sugioka
authors.affiliation: Departments of Orthopaedic Surgery, Osaka City University Medical School, Osaka, 545-8585, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Mamoto
authors.affiliation: Department of Health and Sports Sciences, Mukogawa Women's University, Hyogo, 663-8558, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Wakitani
authors.affiliation: Center for Senile Degenerative Disorders, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan. tatsuya@med.osaka-cu.ac.jp.|Search Institute for Bone and Arthritis, Shirahama Health and Welfare Foundation, Wakayama, 649-2211, Japan. tatsuya@med.osaka-cu.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Koike
authors.affiliation: Departments of Orthopaedic Surgery, Osaka City University Medical School, Osaka, 545-8585, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001168:Arthritis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D053583:Interleukin-1beta / Q000097:blood*; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012074:Remission Induction; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C508585:IL1B protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; C036309:fibrin fragment D; C502936:tocilizumab
keywords: Biomarker; D-dimer; Fibrinogen; Interleukin-1 beta; Predictor; Rheumatoid arthritis; Tocilizumab