Heterogeneous Disease Trajectories Explain Variable Radiographic, Function and Quality of Life Outcomes in the Canadian Early Arthritis Cohort (CATCH)

Cheryl Barnabe, Ye Sun, Gilles Boire, Carol A Hitchon, Boulos Haraoui, J Carter Thorne, Diane Tin, Désirée van der Heijde, Jeffrey R Curtis, Shahin Jamal, Janet E Pope, Edward C Keystone, Susan Bartlett, Vivian P Bykerk, CATCH Investigators, Vivian Bykerk, Majed Kraishi, Michel Zummer, Murray Baron, Ines Colmegna, Boulos Haraoui, Gilles Boire, Louis Bessette, Pooneh Akhavan, Ed Keystone, Laurence Rubin, Janet Pope, William Bensen, Maggie Larche, Carter Thorne, Vandana Ahluwalia, Carol Hitchon, Bindu Nair, Cheryl Barnabe, Glen Hazlewood, Dianne Mosher, Chris Penney, Christopher Lyddell, Shahin Jamal, Alice Klinckhoff, Cheryl Barnabe, Ye Sun, Gilles Boire, Carol A Hitchon, Boulos Haraoui, J Carter Thorne, Diane Tin, Désirée van der Heijde, Jeffrey R Curtis, Shahin Jamal, Janet E Pope, Edward C Keystone, Susan Bartlett, Vivian P Bykerk, CATCH Investigators, Vivian Bykerk, Majed Kraishi, Michel Zummer, Murray Baron, Ines Colmegna, Boulos Haraoui, Gilles Boire, Louis Bessette, Pooneh Akhavan, Ed Keystone, Laurence Rubin, Janet Pope, William Bensen, Maggie Larche, Carter Thorne, Vandana Ahluwalia, Carol Hitchon, Bindu Nair, Cheryl Barnabe, Glen Hazlewood, Dianne Mosher, Chris Penney, Christopher Lyddell, Shahin Jamal, Alice Klinckhoff

Abstract

Our objective was to identify distinct trajectories of disease activity state (DAS) and assess variation in radiographic progression, function and quality of life over the first two years of early rheumatoid arthritis (ERA). The CATCH (Canadian early ArThritis CoHort) is a prospective study recruiting ERA patients from academic and community rheumatology clinics in Canada. Sequential DAS28 scores were used to identify five mutually exclusive groups in the cohort (n = 1,586) using growth-based trajectory modeling. Distinguishing baseline sociodemographic and disease variables, treatment required, and differences in radiographic progression and quality of life measures over two years were assessed. The trajectory groups are characterized as: Group 1 (20%) initial high DAS improving rapidly to remission (REM); Group 2 (21%) initial moderate DAS improving rapidly to REM; Group 3 (30%) initial moderate DAS improving gradually to low DAS; Group 4 (19%) initial high DAS improving continuously to low DAS; and Group 5 (10%) initial high DAS improving gradually only to moderate DAS. Groups differed significantly in age, sex, race, education, employment, income and presence of comorbidities. Group 5 had persistent steroid requirements and the highest biologic therapy use. Group 2 had lower odds (OR 0.22, 95%CI 0.09 to 0.58) and Group 4 higher odds (OR 1.94, 95%CI 0.90 to 4.20) of radiographic progression compared to Group 1. Group 1 had the best improvement in physical function (Health Assessment Questionnaire 1.08 (SD 0.68) units), Physical Component Score (16.4 (SD 10.2) units), Mental Component Score (9.7 (SD 12.5) units) and fatigue (4.1 (SD 3.3) units). In conclusion, distinct disease activity state trajectories explain variable outcomes in ERA. Early prediction of disease course to tailor therapy and addressing social determinants of health could optimize outcomes.

Conflict of interest statement

Competing Interests: The CATCH study was designed and implemented by the investigators and financially supported initially by Amgen Canada Inc. and Pfizer Canada Inc. via an unrestricted research grant since inception of CATCH. As of 2011, further support was provided by Hoffmann-La Roche Ltd., United Chemicals of Belgium (UCB) Canada Inc., Bristol-Myers Squibb Canada Co., Abbott Laboratories Ltd., and Janssen Biotech Inc. (a wholly owned subsidiary of Johnson & Johnson Inc.). Cheryl Barnabe received advisory board honoraria from the following commercial sources: Amgen Canada Inc. and Pfizer Canada Inc. Hoffmann-La Roche Ltd., United Chemicals of Belgium (UCB) Canada Inc., Bristol-Myers Squibb Canada Co., Abbott Laboratories Ltd., and Janssen Biotech Inc. (a wholly owned subsidiary of Johnson & Johnson Inc.). There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Cohort Derivation.
Fig 1. Cohort Derivation.
Flow diagram of subjects included in the study.
Fig 2. Predicted Group Trajectories in Early…
Fig 2. Predicted Group Trajectories in Early Rheumatoid Arthritis based on DAS28 with 95% CI (n = 1,586).
Five predicted group trajectories (solid or dashed lines) and 95% confidence interval limits (shaded) are depicted from the group-based trajectory modelling. Percentages reflect the predicted proportion of subjects in each group, which differs marginally from the actual group characterization in the dataset.
Fig 3. Treatment by Trajectory Group.
Fig 3. Treatment by Trajectory Group.
(A) Group Proportion on Methotrexate (≥15 mg), by Visit Month. (B) Group Proportion on Combination Methotrexate and DMARD Therapy, by Visit Month. (C) Group Proportion on Biologics, by Visit Month. (D) Group Proportion on Corticosteroids, by Visit Month.
Fig 4. Significant Radiographic Progression During First…
Fig 4. Significant Radiographic Progression During First Year of Follow-up, by Trajectory Group.

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