Etanercept-Methotrexate Combination Therapy Initiators Have Greater Adherence and Persistence Than Triple Therapy Initiators With Rheumatoid Arthritis

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Arthritis Care & Research
Volume 67, Issue 12, pages 1656–1663, December 2015

Machaon Bonafede et al.

Objective
To estimate adherence and persistence with etanercept plus methotrexate (ETN-MTX) combination therapy and MTX, hydroxychloroquine, and sulfasalazine triple therapy at 1 year following treatment initiation in adults with rheumatoid arthritis (RA).

Methods
This retrospective analysis used data from the Truven Health MarketScan Commercial and Medicare Supplemental databases from January 2009 to July 2013. Adherence was defined as having percentage of days covered >80% for all drugs within each regimen. Persistence was defined as no treatment gap >45 days for any drug and no addition or switching to other disease-modifying antirheumatic drugs. Multiple logistic regression models were employed in the analyses to control for potential confounders.

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Perspectives From Masters in Rheumatology and Autoimmunity: Can We Get Closer to a Cure for Rheumatoid Arthritis?

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An interesting review from two Masters of Rheumatology. Are we close to cure Rheumatoid Arthritis? Don’t miss it

Marc Feldmann and Ravinder N. Maini

Article first published online: 26 AUG 2015

We have lived through amazing times in rheumatology, with progress in drug discovery based on intuition (e.g., gold, sulfasalazine) to discovery driven by advances in understanding of the molecular basis of disease pathogenesis and application of technology, chiefly based on molecular biology and immunology. When we were medical students autoimmunity was a vague concept, inflammatory mediators were a few small chemicals, cellular signaling was a mystery, and therapeutics was dominated by the organic medicinal chemists. Rheumatoid arthritis (RA) was an incurable, painful, life-damaging, and life-shortening disease [1] for which prior attempts at a cure, as with the lauded discovery of corticosteroids, ended lamentably [2]. But through empiricism, there was progress, even without access to modern technological tools.

Abatacept more effective in RA patients with high levels ACPA

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Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial

Sokolove J, et al. Ann Rheum Dis 2015;0:1–6. doi:10.1136

ABSTRACT Objectives To examine whether baseline anti-cyclic citrullinated peptide-2 (CCP2) antibody status and concentration correlated with clinical outcomes in patients treated with abatacept or adalimumab on background methotrexate (MTX) in the 2-year AMPLE (Abatacept versus adaliMumab comParison in bioLogicnaïvE rheumatoid arthritis subjects with background MTX) study. Methods In this exploratory analysis, anti-CCP2 antibody concentration was measured at baseline, and antibody-positive patients were divided into equal quartiles, Q1–Q4, representing increasing antibody concentrations. Clinical outcomes analysed by baseline anti-CCP2 status and quartile included change from baseline in disease activity and disability and remission rates. Results Baseline characteristics were generally comparable across quartiles and treatment groups. In both treatment groups, anti-CCP2 antibody-negative patients responded less well than antibody-positive patients. At year 2, improvements in disease activity and disability and remission rates were similar across Q1–Q3, but were numerically higher in Q4 in the abatacept group; in contrast, treatment effects were similar across all quartiles in the adalimumab group. Conclusions In AMPLE, baseline anti-CCP2 positivity was associated with a better response for abatacept and adalimumab. Patients with the highest baseline antiCCP2 antibody concentrations had better clinical response with abatacept than patients with lower concentrations, an association that was not observed with adalimumab.

Comparison of the efficacies of abatacept and tocilizumab in patients with rheumatoid arthritis by propensity score matching

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Ann Rheum Dis doi:10.1136/annrheumdis-2015-20778 Satoshi KuboShingo NakayamadaKazuhisa NakanoShintaro HirataShunsuke FukuyoIppei MiyagawaKentaro HanamiKazuyoshi Saito,Yoshiya Tanaka

Abstract

Objective To compare the clinical outcomes at 1 year after the treatment with either abatacept or tocilizumab in patients with rheumatoid arthritis in routine clinical practice.

Methods To overcome potential bias in allocation to treatment with abatacept or tocilizumab, a propensity score based on multiple baseline characteristics variables was calculated and 102 of 194 patients treated with abatacept and 102 of 273 patients treated with tocilizumab were statistically extracted. Clinical outcomes were assessed.

Results The baseline characteristics were statistically comparable. At week 52, 72%/69% of patients (abatacept/tocilizumab) were still receiving treatment. The Simplified Disease Activity Index (SDAI) decreased from 28.7/27.7 at baseline to 14.0/12.5 at week 52 with abatacept/tocilizumab, respectively. At week 52, the remission rates for abatacept/tocilizumab were 18%/20%, respectively. No statistical difference in clinical efficacy between abatacept and tocilizumab was seen. Moreover, a subanalysis showed that abatacept and tocilizumab had similar effectiveness with or without methotrexate. However, prognostic factors at baseline contributing to the Clinical Disease Activity Index at week 52 were different between the two groups by multiple regression analysis. A higher rheumatoid factor (RF) titre and lower SDAI at baseline were associated with lower SDAI at week 52 in patients treated with abatacept, whereas patients receiving tocilizumab with a lower Health Assessment Questionnaire Disability Index and who were biologics-naïve at baseline had a lower SDAI at week 52.

Conclusions We compared patients treated with abatacept or tocilizumab after statistical adjustment by propensity score matching. Clinical efficacies, including SDAI, were comparable in both treatment groups. However, the predictive factors were different: abatacept appears to benefit patients with higher RF titres, and early induction of tocilizumab is an important factor for good clinical efficacy.

Epratuzumab Results Disappointing, but Adalimumab Promising

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The Rheumatologist

August 19, 2015 • By

Epratuzumab is a monoclonal antibody targeting CD22, which modulates B cells. Epratuzumab is thought to bind to CD22, resulting in diminishedsystemic lupus erythematosus (SLE)–related hyperactivity of B cells without depleting them.

In each study, patients (n = 786 for EMBODY 1; n = 788 for EMBODY 2) received placebo or treatment with 2,400 mg epratuzumab over four, 12-week treatment cycles administered as 600 mg every week for four weeks or 1,200 mg every two weeks for four weeks. Patients were all receiving corticosteroids at the beginning of the studies, along with either epratuzumab or placebo. Immunosuppressant and antimalarial drugs were given per their standard therapy regimen.

Adalimumab Effective in Juvenile ERA
In other drug news, adalimumab was recently studied in a Phase 3, multicenter, randomized, double-blind trial in patients age 6 years to younger than 18 years withenthesitis-related arthritis (ERA) for 12 weeks (n = 46).2 Patients received 24 mg/m2 adalimumab (maximum dose of 40 mg every other week) or placebo, followed by adalimumab for up to 192 weeks in an open-label design. If a predefined worsening occurred, early escape to the open-label adalimumab treatment period was available at Week 4. Adverse events were evaluated throughout the study. The primary endpoint was the percentage change from baseline at Week 12 in the number of active joints with arthritis (AJC). At baseline, the mean patient age was 12.9 years, with a mean duration of ERA symptoms being 2.6 years. The mean AJC was 7.8 and the mean enthesitis count was 8.1.

At Week 12, there was a 63% reduction in the number of joints with active disease in the adalimumab-treated patients compared with placebo-treated patients (12% reduction). By Week 52, there was an 89% reduction from baseline in the number of joints with active disease. (All patients had been receiving adalimumab after Week 12.) By Week 52, 35% of patients had stopped taking non-steroidal antiinflammatory drugs, 15% had stopped taking corticosteroids, and 11% were no longer taking other disease modifying antirheumatic drugs (e.g., sulfasalazine or methotrexate).

The most common adverse effects were upper respiratory infections, injection site pain, gastroenteritis, ALT elevations, abdominal pain nausea and syncope. Serious adverse events included worsening of ERA and appendicitis.

Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

  1. UCB. News release: UCB announces Phase 3 clinical trial program for epratuzumab in systemic lupus erythematosus did not meet primary endpoint. 2015 July 28.
  2. Burgos-Varga R, Tse SML, Horneff G, et al. Adalimumab in pediatric enthesitis-related arthritis A randomized, double-blind, placebo-controlled, multicenter study of adalimumab in pediatric patients with enthesitis-related arthritis.Arthritis Care Res (Hoboken). 2015 Jul 20. doi: 10.1002/acr.22657. [Epub ahead of print]

Similar RA Outcomes with Abatacept & Tocilizumab

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The Rheumatologist

August 17, 2015 • By Will Boggs, MD

NEW YORK (Reuters Health)—Clinical outcomes of rheumatoid arthritis (RA) are similar with abatacept and tocilizumab treatment, but the factors that predict efficacy differ for the two agents.

Abatacept targets T cells, whereas tocilizumab targets interleukin-6, and both are used in patients whose disease has proven refractory to methotrexate.

Dr. Tanaka’s team used a propensity score-matched analysis to compare clinical outcomes of abatacept and tocilizumab treatment of 102 patients in each group and sought to determine the predictive factors of the efficacy of each treatment.

Retention rates at 52 weeks were similar for abatacept (71.6%) and tocilizumab (68.6%). Discontinuation for inadequate effect was more common with abatacept (22.5%) than with tocilizumab (16.7%), according to the Aug. 5 online report in Annals of the Rheumatic Diseases.

Patients experienced similar improvements in Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire Disability Index (HAQ-DI), and Clinical Disease Activity Index (CDAI) with abatacept and tocilizumab treatment.

In contrast, the improvement in DAS28-ESR (the 28-joint count disease activity score-erythrocyte sedimentation rate) was greater with tocilizumab than with abatacept.

Lower baseline SDAI and higher baseline rheumatoid factor titer predicted better CDAI outcomes of abatacept treatment, whereas previous use of a biological agent and lower baseline HAQ-DI score predicted better tocilizumab outcomes.

“These factors should be considered when choosing one of these drugs,” Dr. Tanaka said. “Thus, this report may contribute (to) progress in ‘precision medicine’ in the field of RA.”

Lupus Nephritis. MMF not superior to AZA as maintenance therapy

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Nature Reviews Rheumatology 11, 258 (2015) doi:10.1038/nrrheum.2015.47
Published online 31 March 2015

The 10-year follow-up data from the MAINTAIN nephritis trial showed that mycophenolate mofetil (MMF) was not superior to azathioprine (AZA) as maintenance therapy for a population of white patients with proliferative lupus nephritis. Survival, kidney function, 24 h proteinuria and renal flares were assessed in 92 of 105 patients originally…