Association of Baseline Peptidylarginine Deiminase 4 Autoantibodies With Favorable Response to Treatment Escalation in Rheumatoid Arthritis

Erika Darrah, Fang Yu, Laura C. Cappelli, Antony Rosen, James Robert O'Dell, Ted R Mikuls

Research output: Contribution to journalArticle

Abstract

Objective: To determine if the baseline presence of autoantibodies to peptidylarginine deiminase 4 (PAD4) predicts therapeutic response to biologic and conventional disease-modifying antirheumatic drugs (DMARDs) 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-PAD4 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 (DAS28), and erosive disease was quantified using the Sharp/van der Heijde scoring method. Generalized estimating equations (GEEs) were used to model the clinical responses to treatment in patients with and those without baseline anti-PAD4 antibodies. Results: Anti-PAD4 antibody positivity was associated with male sex, a history of never smoking, and anti–citrullinated protein antibodies. At baseline, patients with anti-PAD4 antibodies had longer disease duration and significantly more radiographic joint damage than anti-PAD4–negative patients, but did not differ in disease activity according to the DAS28. In unadjusted analyses and multivariable GEE models, patients with anti-PAD4 antibodies exhibited greater improvements in DAS28 (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-PAD4 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.

Original languageEnglish (US)
Pages (from-to)696-702
Number of pages7
JournalArthritis and Rheumatology
Volume71
Issue number5
DOIs
StatePublished - May 1 2019

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Autoantibodies
Rheumatoid Arthritis
Joints
Antibodies
Methotrexate
Antirheumatic Agents
Therapeutics
Hydroxychloroquine
protein-arginine deiminase
Sulfasalazine
Immunoprecipitation
Research Design
Smoking
Serum

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Association of Baseline Peptidylarginine Deiminase 4 Autoantibodies With Favorable Response to Treatment Escalation in Rheumatoid Arthritis. / Darrah, Erika; Yu, Fang; Cappelli, Laura C.; Rosen, Antony; O'Dell, James Robert; Mikuls, Ted R.

In: Arthritis and Rheumatology, Vol. 71, No. 5, 01.05.2019, p. 696-702.

Research output: Contribution to journalArticle

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abstract = "Objective: To determine if the baseline presence of autoantibodies to peptidylarginine deiminase 4 (PAD4) predicts therapeutic response to biologic and conventional disease-modifying antirheumatic drugs (DMARDs) 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-PAD4 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 (DAS28), and erosive disease was quantified using the Sharp/van der Heijde scoring method. Generalized estimating equations (GEEs) were used to model the clinical responses to treatment in patients with and those without baseline anti-PAD4 antibodies. Results: Anti-PAD4 antibody positivity was associated with male sex, a history of never smoking, and anti–citrullinated protein antibodies. At baseline, patients with anti-PAD4 antibodies had longer disease duration and significantly more radiographic joint damage than anti-PAD4–negative patients, but did not differ in disease activity according to the DAS28. In unadjusted analyses and multivariable GEE models, patients with anti-PAD4 antibodies exhibited greater improvements in DAS28 (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-PAD4 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.",
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