The online version of this article (https://doi.org/10.1186/s13075-017-1484-9) contains supplementary material, which is available to authorized users.
The aim was to analyze characteristics that predict remission induction and subsequent loss of remission in patients with moderately active rheumatoid arthritis (RA) who received full-dose combination etanercept plus methotrexate induction therapy followed by reduced-dose etanercept or etanercept withdrawal.
Patients with Disease Activity Score based on 28-joint count (DAS28) >3.2 and ≤5.1 received open-label etanercept 50 mg once weekly (QW) plus methotrexate for 36 weeks. Those who achieved DAS28 low disease activity by 36 weeks were randomized to double-blind treatment with etanercept 50 mg or 25 mg QW plus methotrexate or placebo plus methotrexate for 52 weeks. All analyses were adjusted for the continuous baseline variables of their respective remission outcomes.
Younger age, body mass index (BMI) <30 kg/m2, and lower Health Assessment Questionnaire (HAQ) score at baseline were significant predictors of week-36 remission (P < 0.05) based on DAS28, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI). Baseline DAS28, SDAI, and CDAI were significantly predictive of all three remission endpoints (P < 0.05). For all three treatments, the strongest predictors of loss of DAS28 remission included failure to achieve sustained remission (DAS28 < 2.6 at weeks 12, 20, 28, and 36) with induction therapy, higher DAS28/SDAI/CDAI at randomization and at 1 month, increase in DAS28/SDAI/CDAI at 1 month, and increase in DAS28/CDAI/SDAI components and patient-reported outcomes (PROs) at 1 month. With the exception of not achieving sustained remission, very similar significant predictors were observed for loss of SDAI and CDAI remission.
These findings suggest that patients with moderately active RA who are younger and have lower BMI, lower HAQ, and lower disease activity at baseline are most likely to achieve remission when receiving combination etanercept and methotrexate induction therapy. In addition, patients who fail to achieve sustained remission with induction therapy and those with worse disease activity and PROs at early time points after initiating maintenance therapy with a full-dose or reduced-dose etanercept-methotrexate regimen or methotrexate monotherapy are most likely to lose remission across all treatment arms. These findings may help guide clinicians’ decision-making as they treat patients to remission and beyond.
ClinicalTrials.gov, NCT00565409. Registered on 28 November 2007
Additional file 1: Appendix 1 and Appendix 2. (DOCX 22 kb)13075_2017_1484_MOESM1_ESM.docx
Additional file 2: Figure S1. Summary of patient disposition in the open-label and double-blind periods. CDAI Clinical Disease Activity Index, DAS28 Disease Activity Score based on a 28-joint count, ETN etanercept, LDA low disease activity, MTX methotrexate, QW once weekly, SDAI Simplified Disease Activity Index. (EPS 1688 kb)13075_2017_1484_MOESM2_ESM.eps
Additional file 3: Figure S2. Predicted probability (95% CI) of the loss of SDAI remission and LDA (a) and the loss of CDAI remission and LDA (b) in patients receiving reduced-dose combination therapy or methotrexate monotherapy in the double-blind period based on mean SDAI/CDAI at week 36 of the open-label period, using logistic regression models. Circles at the top indicate patients who lost response; circles at bottom indicate patients who did not lose response; smooth line, model-predicted probability of loss of response as a function of week-36 DAS28; shadowed area, 95% CI. (EPS 2683 kb)13075_2017_1484_MOESM3_ESM.eps
Additional file 4: Figure S3. Mean DAS28 levels in patients who lost remission at ≥1 time point and who never lost remission in the double-blind period. mITT population in double-blind period who had remission at week 36. CI confidence interval, DAS28 Disease Activity Score based on a 28-joint count, ETN etanercept, mITT modified intent-to-treat, MTX methotrexate. (EPS 1406 kb)13075_2017_1484_MOESM4_ESM.eps
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- Predictors of remission with etanercept-methotrexate induction therapy and loss of remission with etanercept maintenance, reduction, or withdrawal in moderately active rheumatoid arthritis: results of the PRESERVE trial
Josef S. Smolen
Andrew S. Koenig
Thomas V. Jones
- BioMed Central
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