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

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.

SUBMITTER: Collins JE

PROVIDER: S-EPMC7011418 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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

Collins Jamie E JE Johansson Fredrik D FD Gale Sara S Kim Seoyoung S Shrestha Swastina S Sontag David D Stratton Jacklyn J Trinh Huong H Xu Chang C Losina Elena E Solomon Daniel H DH

ACR open rheumatology 20200101 2

<h4>Objective</h4>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.<h4>Methods</h4>We identified four TCZ monotherapy randomized controlled trials in RA and chose two for derivation and two for internal validation. Remissio ...[more]

PMID: 32043832

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Project description:BACKGROUND:Reliable assessment of remission is important for the optimal management of rheumatoid arthritis (RA) patients. In this study, we used the multi-biomarker disease activity (MBDA) test to explore the role of biomarkers in predicting point remission and sustained remission. METHODS:RA patients on >?6?months stable therapy in stable low disease activity (DAS28-ESR ??3.2) were assessed every 3?months for 1?year. Baseline, intermittent (IR) and sustained (SR) remission were defined by DAS28-ESR, DAS28-CRP, simple disease activity index (SDAI), clinical disease activity index (CDAI) and ACR/EULAR Boolean criteria. Patients not fulfilling any remission criteria at baseline were classified as 'low disease activity state' (LDAS). Patients not fulfilling any remission criteria over 1?year were classified as 'persistent disease activity' (PDA). MBDA score was measured at baseline/3/6?months. The baseline MBDA score, the 6-month time-integrated MBDA score and MBDA biomarkers were used for analyses. The area under the receiver operating characteristic curve (AUROC) assessed the ability of the MBDA score to discriminate between remission and non-remission. Biomarkers were analysed at baseline using the Mann-Whitney test and over time using the Jonckheere-Terpstra trend test. RESULTS:Of 148 patients, 27% were in the LDAS, 65% DAS28-ESR remission, 51% DAS28-CRP remission, 40% SDAI remission, 43% CDAI remission and 25% ACR/EULAR Boolean remission at baseline. Over 1?year, 9% of patients were classified as PDA. IR and SR were achieved in 42%/47% by DAS28-ESR, 46%/29% by DAS28-CRP, 45%/20% by SDAI, 44%/21% by CDAI and 35%/9% by ACR/EULAR Boolean criteria, respectively. By all remission criteria, baseline MBDA score discriminated baseline remission (AUROCs 0.68-0.75) and IR/SR (AUROCs 0.65-0.74). The 6-month time-integrated MBDA score discriminated IR/SR (AUROCs 0.65-0.79). Baseline MBDA score and concentrations of IL-6, leptin, SAA and CRP were significantly lower in all baseline remission criteria groups vs LDAS. They and the 6-month time-integrated values were lower among patients who achieved IR/SR vs PDA over 1?year. CONCLUSIONS:This study demonstrated that the MBDA score and its biomarkers IL-6, leptin, SAA and CRP differentiated between small differences in disease activity (i.e. between low disease activity and remission states). They were also predictors of remission over 1 year.

Project description:IntroductionTocilizumab (TCZ) monotherapy has been proven as an effective treatment for rheumatoid arthritis (RA) in clinical trials. However, there are limited data available regarding the effectiveness of TCZ monotherapy in real-world clinical settings in the United States. The objective of this study was to evaluate the impact of TCZ monotherapy on disease activity and patient-reported outcomes (PROs) in a US-based observational cohort of patients with RA seen in routine clinical practice.MethodsEligible patients had active RA, no prior use of TCZ, and initiated TCZ as monotherapy. Changes in disease activity and PROs were assessed 1 year after TCZ initiation for the overall cohort and stratified by number of prior tumor necrosis factor inhibitors (TNFis; 0, 1, or ≥2). Primary outcomes were change in Clinical Disease Activity Index (CDAI); change in patient global disease activity, pain, fatigue; and the proportions of patients with improvement in modified Health Assessment Questionnaire (mHAQ), morning stiffness, and EQ-5D.ResultsOf 255 eligible TCZ monotherapy initiators, 9.4% were TNFi naive, 36.5% had one prior TNFi, and 54.1% had ≥2 prior TNFis. Clinical and PRO measures indicated that patients were substantially impacted by their disease at baseline. The median decrease in CDAI from baseline to 1 year was 9.8 and median patient global and pain scores improved by 10 mm, indicative of clinically meaningful improvement; the median fatigue score improved by 5 mm. Approximately 26% of patients reported clinically meaningful improvement in mHAQ, 54% experienced improvement in morning stiffness, and 20% to 36% experienced improvement in EQ-5D domains (walking, self-care, usual activities, pain/discomfort, and anxiety/depression). Improvements were similar across TNFi groups.ConclusionsPatients with active, refractory RA who initiated TCZ monotherapy experienced improvements in both composite disease activity scores and PROs at 1 year, regardless of prior TNFi exposure.FundingCorrona, LLC and Genentech.

Project description:Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by joint pain, swelling, stiffness, and progressive destruction of the small joints of the hands and feet. Treatment of RA has improved over the past decade. With multiple cytokines well-known now to play a role in the pathogenesis of RA, including tumor necrosis factor alpha, interleukin (IL)-1?, and IL-6, many targeted biological treatments against these cytokines have emerged, changing the treatment of this disease. Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody against the IL-6 receptor and has been approved in many countries, including the United States, for the treatment of moderate to severe RA in patients who have not adequately responded to one or more disease-modifying antirheumatic drugs (DMARDs) or cannot tolerate other approved drug classes for RA. The aim of this review is to discuss the role of IL-6 in RA, and to provide an overview of the mode of action, pharmacokinetics, and safety of TCZ. Furthermore, efficacy studies of TCZ as both monotherapy and combination therapy will be evaluated. There have been several important clinical trials evaluating the efficacy and safety of TCZ in RA patients; this review summarizes this data from 14 key trials with emphasis on Phase III trials. Review of these trials provides strong evidence that its use, both as monotherapy and in combination with methotrexate or other DMARDs, is an effective treatment in reducing the signs and symptoms of RA. TCZ showed tolerable safety but care is required for its use since there are some important safety concerns including elevated liver enzymes, elevated low-density lipoprotein, infections, and gastrointestinal perforations. Additionally, given the efficacy of TCZ in the treatment of RA, this review discusses how TCZ may be beneficial in the treatment of other autoimmune diseases, spinal disease, cardiovascular disease, organ transplantation, and malignancies where elevated levels of IL-6 may play a role in the pathogenesis of these diseases.

Project description:IntroductionControlled clinical studies have shown that the efficacy of tocilizumab (TCZ) monotherapy is superior to that of tumor necrosis factor inhibitor (TNFi) monotherapy and comparable to that of TCZ plus methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). This study compared the real-world effectiveness of TCZ monotherapy vs. TNFis plus MTX in US patients with RA.MethodsTCZ-naïve patients from the Corrona RA registry with prior exposure to ≥ 1 TNFi who initiated TCZ monotherapy or TNFi + MTX were included. Outcomes included mean change in Clinical Disease Activity Index (CDAI), achievement of low disease activity (LDA; CDAI ≤ 10), achievement of modified American College of Rheumatology (mACR) 20/50 responses, and mean change in modified Health Assessment Questionnaire (mHAQ) at 6 months. Patients initiating TNFi + MTX were grouped by MTX dose (≤ 10 mg; > 10 to ≤ 15 mg; > 15 to ≤ 20 mg; > 20 mg); outcomes in each group were compared with TCZ monotherapy using trimmed populations (excluding patients outside the propensity score distribution overlap).ResultsPatients in all groups experienced improvement in CDAI at 6 months (mean change, - 6.9 to - 9.7), with no significant differences between the TCZ monotherapy and TNFi + MTX groups. Achievement of LDA and mACR responses at 6 months were comparable between the TCZ monotherapy and TNFi + MTX groups; overall, 26.8-38.0% of patients achieved LDA, 24.3-37.6% achieved mACR20 response and 13.2-20.8% achieved mACR50 response. The mean change in mHAQ at 6 months was - 0.1 in all groups.ConclusionsIn this real-world population of US patients with RA who had prior TNFi exposure, there was no evidence of a difference in the effectiveness of TCZ monotherapy compared with that of TNFi + MTX, regardless of MTX dose, at 6 months for improving RA disease activity.FundingCorrona, LLC. Plain language summary available for this article.

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

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

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