Prognosis of seronegative patients in a large prospective cohort of patients with early inflammatory arthritis.

Lillian Barra Janet E Pope John E Orav Gilles Boire Boulos Haraoui Carol Hitchon Edward C Keystone J Carter Thorne Diane Tin Vivian P Bykerk

J Rheumatol

From the Department of Medicine, Division of Rheumatology, St. Joseph's Health Care London, University of Western Ontario, London; Rebecca McDonald Center for Arthritis and Autoimmune Disease, Mount Sinai Hospital, University of Toronto, Toronto; Southlake Regional Health Centre, Newmarket, Ontario; Rheumatology Division, Université de Sherbrooke, Sherbrooke; Rheumatic Disease Unit, Institut de Rheumatologie, Université de Montréal, Montreal, Quebec; Arthritis Center, University of Manitoba, Winnipeg, Manitoba, Canada; Inflammatory Arthritis Center, Hospital for Special Surgery, Department of Biostatistics, Harvard University, Boston, Massachusetts; Weill Cornell Medical College, Cornell University, New York, New York, USA.Dr. Barra has received honoraria from Hoffmann-La Roche Ltd., Amgen Canada Inc., AbbVie, and United Chemicals of Belgium (UCB). The CATCH study was designed and implemented by the investigators and financially supported initially by Amgen Canada Inc. and Pfizer Canada Inc. through an unrestricted research grant since inception of CATCH. As of 2011, further support was provided by Hoffmann-La Roche Ltd., UCB Canada Inc., Bristol-Myers Squibb Canada Co., Abbott Laboratories Ltd., and Janssen Biotech Inc. (a wholly owned subsidiary of Johnson & Johnson Inc.).L. Barra, MD, MPH; J.E. Pope, MD, MPH, Department of Medicine, Division of Rheumatology, St. Joseph's Health Care London, University of Western Ontario; J.E. Orav, PhD, Department of Biostatistics, Harvard University; G. Boire, MD, MSc, Rheumatology Division, Université de Sherbrooke; B. Haraoui, MD, Rheumatic Disease Unit, Institut de Rheumatologie, Université de Montréal; C. Hitchon, MD, MSc, Arthritis Center, University of Manitoba; E.C. Keystone, MD, Rebecca McDonald Center for Arthritis and Autoimmune Disease, Mount Sinai Hospital, University of Toronto; J.C. Thorne, MD; D. Tin, BPharm, Southlake Regional Health Centre; V.P. Bykerk, MD, Rebecca McDonald Center for Arthritis and Autoimm

Published: December 2014

Objective: Rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) are believed to be associated with more severe rheumatoid arthritis; however, studies in early inflammatory arthritis (EIA) have yielded conflicting results. Our study determined the prognosis of baseline ACPA-negative and RF-negative patients.

Methods: Patients enrolled in the Canadian Early Arthritis Cohort had IgM RF and IgG anticyclic citrullinated peptide antibodies 2 (anti-CCP2) measured at baseline. Remission was defined as a Disease Activity Score of 28 joints (DAS28) < 2.6 using logistic regression accounting for confounders at 12-month and 24-month followup.

Results: Of the 841 patients, 216 (26%) were negative for both RF and anti-CCP2. Compared to seropositive subjects, seronegative subjects were older (57 ± 15 vs 51 ± 14 yrs), more males proportionately (31% vs 23%), and had shorter length of symptoms (166 ± 87 vs 192 ± 98 days), and at baseline had higher mean swollen joint count (SJC; 8.8 ± 6.8 vs 6.5 ± 5.6), DAS28 (5.0 ± 1.6 vs 4.8 ± 1.5), and erosive disease (32% vs 24%, p < 0.05). Treatment was similar between the 2 groups. At 24-month followup, seronegative compared to seropositive subjects had greater mean change (Δ ± SD) in disease activity measures: ΔSJC counts (-6.9 ± 7.0 vs -5.1 ± 5.9), ΔDAS28 (-2.4 ± 2.0 vs -1.8 ± 1.8), and ΔC-reactive protein (-11.0 ± 17.9 vs -6.4 ± 17.5, p < 0.05). Accounting for confounders, antibody status was not significantly associated with remission. However, at 12-month followup, ACPA-positive subjects were independently more likely to have new erosive disease (OR 2.94, 95% CI 1.45-5.94).

Conclusion: Although seronegative subjects with EIA have higher baseline DAS28 compared to seropositive subjects, they have a good response to treatment and are less likely to develop erosive disease during followup.

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