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      Predicting Remission Among Patients With Rheumatoid Arthritis Starting Tocilizumab Monotherapy: Model Derivation and Remission Score Development

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          Abstract

          Objective

          Most patients with rheumatoid arthritis ( RA) strive to consolidate their treatment from methotrexate combinations. The objective of this analysis was to identify patients with RA most likely to achieve remission with tocilizumab ( TCZ) monotherapy by developing and validating a prediction model and associated remission score.

          Methods

          We identified four TCZ monotherapy randomized controlled trials in RA and chose two for derivation and two for internal validation. Remission was defined as a Clinical Disease Activity Index score less than 2.8 at 24 weeks post randomization. We used logistic regression to assess the association between each predictor and remission. After selecting variables and assessing model performance in the derivation data set, we assessed model performance in the validation data set. The cohorts were combined to calculate a remission prediction score.

          Results

          The variables selected included younger age, male sex, lower baseline Clinical Disease Activity Index score, shorter RA disease duration, region of the world (Europe and South America [increased odds of remission] versus Asia and North America), no previous exposure to disease‐modifying antirheumatic drugs and/or methotrexate, lower baseline Health Assessment Questionnaire Disability Index score, and baseline hematocrit. The area under the receiver operating characteristic curve was 0.739 in the derivation data set and 0.756 in the validation data set. Patients were categorized into three remission prediction categories based on the remission prediction score: 40% in the low (less than 10% probability of remission), 45% in the intermediate (10%‐25% probability), and 15% in the moderate remission prediction category (greater than 25% probability).

          Conclusion

          We used easily accessible factors to develop a remission prediction score to predict RA remission at 24 weeks after initializing TCZ monotherapy. These results may provide guidance to clinicians tailoring treatment options based on clinical characteristics.

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          Most cited references7

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          Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study

          Background: The anti-interleukin (IL) 6 receptor antibody tocilizumab inhibits signalling of IL6, a key cytokine in rheumatoid arthritis (RA) pathogenesis. Objective: To evaluate through the AMBITION study the efficacy and safety of tocilizumab monotherapy versus methotrexate in patients with active RA for whom previous treatment with methotrexate/biological agents had not failed. Methods: This 24-week, double-blind, double-dummy, parallel-group study, randomised 673 patients to either tocilizumab 8 mg/kg every 4 weeks, or methotrexate, starting at 7.5 mg/week and titrated to 20 mg/week within 8 weeks, or placebo for 8 weeks followed by tocilizumab 8 mg/kg. The primary end point was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 24. Results: The intention-to-treat analysis demonstrated that tocilizumab was better than methotrexate treatment with a higher ACR20 response (69.9 vs 52.5%; p 3×–<5× upper limit of normal (1.0% vs 2.5%), respectively. Conclusion: Tocilizumab monotherapy is better than methotrexate monotherapy, with rapid improvement in RA signs and symptoms, and a favourable benefit–risk, in patients for whom treatment with methotrexate or biological agents has not previously failed. Trial registration number: NCT00109408
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            The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): a review of their usefulness and validity in rheumatoid arthritis.

            Composite indices or pooled indices are useful tools for the evaluation of disease activity in patients with rheumatoid arthritis (RA). They allow the integration of various aspects of the disease into a single numerical value, and may therefore facilitate consistent patient care and improve patient compliance, which both can lead to improved outcomes. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) are two new tools for the evaluation of disease activity in RA. They have been developed to provide physicians and patients with simple and more comprehensible instruments. Moreover, the CDAI is the only composite index that does not incorporate an acute phase response and can therefore be used to conduct a disease activity evaluation essentially anytime and anywhere. These two new tools have not been developed to replace currently available instruments such as the DAS28, but rather to provide options for different environments. The comparative construct, content, and discriminant validity of all three indices--the DAS28, the SDAI, and the CDAI--allow physicians to base their choice of instrument on their infrastructure and their needs, and all of them can also be used in clinical trials.
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              The Health Assessment Questionnaire (HAQ).

              Patient-reported outcomes (PROs) provide intrinsic knowledge about a patient's health, functional status, symptoms, treatment preferences, satisfaction, and quality of life. They have become an established approach for assessing health outcomes. The Health Assessment Questionnaire (HAQ), introduced in 1980, is among the first PRO instruments designed to represent a model of patient-oriented outcome assessment. The HAQ is based on five patient-centered dimensions: disability, pain, medication effects, costs of care, and mortality. It has been validated by mail, in the office, by telephone, and by comparison with paraprofessional and physician judgments as a reliable instrument, and has been significantly correlated with other PRO instruments. Typically, one of two HAQ versions is used: the Full HAQ, which assesses all five dimensions, and the Short or 2-page HAQ, which contains only the HAQ disability index (HAQ-DI) and the HAQ's patient global and pain visual analog scales (VAS). The HAQ-DI and the global and pain VAS (i.e., the short HAQ) have essentially retained their original content since their inception, while the Full HAQ undergoes periodic revision to address issues of contemporary scientific interest. The HAQ-DI has been translated or culturally adapted into more than 60 different languages or dialects and has become part of the National Institutes of Health "Road-map" Project, the Patient-Reported Outcomes Measurement Information System (PROMIS).
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                Author and article information

                Contributors
                Jcollins13@bwh.harvard.edu
                Journal
                ACR Open Rheumatol
                ACR Open Rheumatol
                10.1002/(ISSN)2578-5745
                ACR2
                ACR Open Rheumatology
                John Wiley and Sons Inc. (Hoboken )
                2578-5745
                01 January 2020
                February 2020
                : 2
                : 2 ( doiID: 10.1002/acr2.v2.2 )
                : 65-73
                Affiliations
                [ 1 ] Brigham and Women's Hospital Boston Massachusetts
                [ 2 ] Institute for Medical Engineering and Science Massachusetts Institute of Technology Cambridge
                [ 3 ] Genentech South San Francisco California
                Author notes
                [*] [* ]Address correspondence to Jamie E. Collins, PhD, Brigham and Women's Hospital, Orthopaedic and Arthritis Center for Outcomes Research, 75 Francis Street, BTM 5016, Boston, MA 02115. E‐mail: Jcollins13@ 123456bwh.harvard.edu .
                Author information
                https://orcid.org/0000-0001-8413-007X
                https://orcid.org/0000-0002-2517-3579
                https://orcid.org/0000-0002-3424-0892
                Article
                ACR211101
                10.1002/acr2.11101
                7011418
                32043832
                9145a37b-40e0-46ed-a513-95b11a250cfe
                © 2020 The Authors. ACR Open Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 01 October 2019
                : 04 October 2019
                Page count
                Figures: 1, Tables: 3, Pages: 9, Words: 7220
                Funding
                Funded by: Roche/Genentech
                Categories
                Original Article
                Original Article
                Custom metadata
                2.0
                February 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.5 mode:remove_FC converted:11.02.2020

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