Radiographic progression based on baseline characteristics from TNF inhibitor biosimilar studies in patients with rheumatoid arthritis.
OBJECTIVE
Phase III clinical trials of the tumour necrosis factor inhibitors SB4, SB2, and SB5 (biosimilars to etanercept, infliximab, and adalimumab, respectively) have demonstrated efficacy in moderate-to-severe rheumatoid arthritis (RA). Data from these trials were used to identify baseline characteristics associated with radiographic progression and to build a matrix risk model for its prediction.


METHODS
Patients with radiographic progression and baseline demographic and disease characteristic data were pooled across the 3 phase III studies of each biosimilar and its reference product. Baseline demographics and disease characteristics were evaluated for their relationship with radiographic progression (1-year mean change in mTSS > 0); 3 factors were selected based on strongest Pearson's correlation coefficient with the change in modified Total Sharp Score. Univariate logistic regression was performed to assess the association between each baseline factor and the rate of radiographic progression, with subsequent matrix model development performed using multivariate logistic regression.


RESULTS
A total of 1371 patients were included in the analysis, with a radiographic progression rate of 27.4%. The 3 baseline predictors of radiographic progression, based on Pearson's correlation coefficient, were 28 swollen joint count (SJC28), C-reactive protein (CRP), and physician global assessment (PhGA). A matrix model showed that the predicted risk of radiographic progression was higher with the increased level of SJC28, CRP, and PhGA (P < 0.001).


CONCLUSIONS
In this pooled analysis of phase III clinical trial data of biosimilars for RA, identifiable baseline factors (SJC28, CRP, and PhGA) associated with radiographic progression were similar to those described in prior studies. Even though radiographic progression was minimal, a small number of patients who have increased SJC28, CRP, and PhGA at baseline should be closely monitored and follow treat-to-target approach.


CLINICAL TRIAL REGISTRATION NUMBERS
EudraCT 2012-005026-30. Registered 30 April 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005026-30/results EudraCT 2012-005733-37. Registered 10 July 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005733-37/results EudraCT 2013-005013-13. Registered 01 April 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-005013-13/results.
['Smolen|Josef S|JS|0000-0002-4302-8877', 'Kang|Young Mo|YM|', 'Yoo|Wan-Hee|WH|', 'Emery|Paul|P|', 'Weinblatt|Michael E|ME|', 'Keystone|Edward C|EC|', 'Genovese|Mark C|MC|', 'Myung|Gihyun|G|', 'Baek|Inyoung|I|', 'Ghil|Jeehoon|J|']
D018501:Antirheumatic Agents D001172:Arthritis, Rheumatoid D059451:Biosimilar Pharmaceuticals D018450:Disease Progression D000068800:Etanercept D006801:Humans D016896:Treatment Outcome D000079424:Tumor Necrosis Factor Inhibitors
TNF inhibitors Biosimilar Rheumatoid arthritis Radiography