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Association of Baseline Peptidylarginine Deiminase 4 Autoantibodies With Favorable Response to Treatment Escalation in Rheumatoid Arthritis
Author(s) -
Darrah Erika,
Yu Fang,
Cappelli Laura C.,
Rosen Antony,
O'Dell James R.,
Mikuls Ted R.
Publication year - 2019
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40791
Subject(s) - medicine , rheumatoid arthritis , sulfasalazine , autoantibody , hydroxychloroquine , methotrexate , antibody , etanercept , arthritis , gastroenterology , rheumatology , immunology , disease , covid-19 , ulcerative colitis , infectious disease (medical specialty)
Objective To determine if the baseline presence of autoantibodies to peptidylarginine deiminase 4 ( PAD 4) predicts therapeutic response to biologic and conventional disease‐modifying antirheumatic drugs ( DMARD s) in patients with rheumatoid arthritis ( RA ) in whom methotrexate ( MTX ) monotherapy was unsuccessful. Methods Baseline serum from 282 RA patients in whom MTX monotherapy was unsuccessful was screened for the presence of anti‐ PAD 4 antibodies by immunoprecipitation. Clinical response to either triple DMARD ( MTX , sulfasalazine, and hydroxychloroquine) or MTX /etanercept combination therapy was determined at 24 and 48 weeks post–treatment initiation. Disease activity was measured using the Disease Activity Score 28‐joint assessment ( DAS 28), and erosive disease was quantified using the Sharp/van der Heijde scoring method. Generalized estimating equations ( GEE s) were used to model the clinical responses to treatment in patients with and those without baseline anti‐ PAD 4 antibodies. Results Anti‐ PAD 4 antibody positivity was associated with male sex, a history of never smoking, and anti–citrullinated protein antibodies. At baseline, patients with anti‐ PAD 4 antibodies had longer disease duration and significantly more radiographic joint damage than anti‐ PAD 4–negative patients, but did not differ in disease activity according to the DAS 28. In unadjusted analyses and multivariable GEE models, patients with anti‐ PAD 4 antibodies exhibited greater improvements in DAS 28 (adjusted P = 0.02 and P = 0.008, respectively) and less radiographic progression (adjusted P = 0.01 and P = 0.002, respectively) compared to anti‐ PAD antibody–negative patients, independent of treatment received. Conclusion Although anti‐ PAD 4 antibodies were associated with worse baseline radiographic joint damage, suggesting a history of active or undiagnosed disease, treatment escalation therapy was more effective in reducing disease activity and slowing the progression of joint damage in this patient subset.