Effectiveness of biologic DMARDs in monotherapy versus in combination with synthetic DMARDs in rheumatoid arthritis: data from the Swiss Clinical Quality Management Registry

Rheumatoid arthritis (RA) is an autoimmune disease that involves multiple joints bilaterally. It is characterized by an inflammation of the tendon (tenosynovitis) resulting in both cartilage destruction and bone erosion. While until the 1990s RA frequently resulted in disability, inability to work, and increased mortality, newer treatment options have made RA a manageable disease. Here, great progress has been made in the development of disease-modifying anti-rheumatic drugs (DMARDs) which target inflammation and thereby prevent further joint damage. The available DMARDs are subdivided into (1) conventional synthetic DMARDs (methotrexate, hydrochloroquine, and sulfadiazine), (2) targeted synthetic DMARDs (pan-JAK- and JAK1/2-inhibitors), and (3) biologic DMARDs (tumor necrosis factor (TNF)-α inhibitors, TNF-receptor (R) inhibitors, IL-6 inhibitors, IL-6R inhibitors, B cell depleting antibodies, and inhibitors of co-stimulatory molecules). While DMARDs have repeatedly demonstrated the potential to greatly improve disease symptoms and prevent disease progression in RA patients, they are associated with considerable side-effects and high financial costs. This review summarizes our current understanding of the underlying pathomechanism, diagnosis of RA, as well as the mode of action, clinical benefits, and side-effects of the currently available DMARDs.

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Clinical quality management in rheumatoid arthritis: putting theory into practice

Rheumatology ◽

10.1093/rheumatology/39.5.542 ◽

2000 ◽

Vol 39 (5) ◽

pp. 542-549 ◽

Cited By ~ 48

Author(s):

E. Uitz ◽

J. Fransen ◽

T. Langenegger ◽

G. Stucki

Keyword(s):

Rheumatoid Arthritis ◽

Quality Management ◽

Clinical Quality

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Risk for lower intestinal perforations in patients with rheumatoid arthritis treated with tocilizumab in comparison to treatment with other biologic or conventional synthetic DMARDs

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2016-209773 ◽

2016 ◽

Vol 76 (3) ◽

pp. 504-510 ◽

Cited By ~ 67

Author(s):

A Strangfeld ◽

A Richter ◽

B Siegmund ◽

P Herzer ◽

K Rockwitz ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Daily Practice ◽

Incidence Rates ◽

Biologic Dmards ◽

Reactive Protein ◽

Intestinal Perforations ◽

History Of ◽

Synthetic Dmards ◽

Randomised Controlled ◽

Factor Α

ObjectiveTo investigate the risk of developing lower intestinal perforations (LIPs) in patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ).MethodsIn 13 310 patients with RA observed in the German biologics register Rheumatoid Arthritis: Observation of Biologic Therapy, 141 serious gastrointestinal events possibly associated with perforations were reported until 31 October 2015. All events were validated independently by two physicians, blinded for treatment exposure.Results37 LIPs (32 in the colon/sigma) were observed in 53 972 patient years (PYs). Only two patients had a history of diverticulitis (one in TCZ). Age, current/cumulative glucocorticoids and non-steroidal anti-inflammatory drugs were significantly associated with the risk of LIP. The crude incidence rate of LIP was significantly increased in TCZ (2.7/1000 PYs) as compared with all other treatments (0.2−0.6/1000 PYs). The adjusted HR (ref: conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs)) in TCZ was 4.48 (95% CI 2.0 to 10.0), in tumour necrosis factor-α inhibitor (TNFi) 1.04 (0.5 to 2.3) and in other biologic DMARDs 0.33 (0.1 to 1.4). 4/11 patients treated with TCZ presented without typical symptoms of LIP (acute abdomen, severe pain). Only one patient had highly elevated C reactive protein (CRP). One quarter of patients died within 30 days after LIP (9/37), 5/11 under TCZ, 2/13 under TNFi and 2/11 under csDMARD treatment.ConclusionsThe incidence rates of LIP under TCZ found in this real world study are in line with those seen in randomised controlled trials of TCZ and higher than in all other DMARD treatments. To ensure safe use of TCZ in daily practice, physicians and patients should be aware that, under TCZ, LIP may occur with mild symptoms only and without CRP elevation.

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Impact of the COVID-19 pandemic on the disease course of patients with inflammatory rheumatic diseases: results from the Swiss Clinical Quality Management cohort

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-218705 ◽

2020 ◽

pp. annrheumdis-2020-218705 ◽

Cited By ~ 1

Author(s):

Adrian Ciurea ◽

Eleftherios Papagiannoulis ◽

Kristina Bürki ◽

Isabell von Loga ◽

Raphael Micheroli ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Quality Management ◽

Disease Activity ◽

Activity Index ◽

Statistical Significance ◽

Disease Activity Index ◽

Inflammatory Rheumatic Diseases ◽

Disease Course ◽

Clinical Quality ◽

Patient Reported

ObjectivesTo investigate whether the transient reduction in rheumatology services imposed by virus containment measures during the COVID-19 pandemic was associated with disease worsening in axial spondyloarthritis (axSpA), rheumatoid arthritis (RA) or psoriatic arthritis (PsA).MethodsPatient-reported disease activity assessed during face-to-face visits and/or via a smartphone application were compared between three periods of each 2 months duration (before, during and after the COVID-19-wave) from January to June 2020 in 666 patients with axSpA, RA and PsA in the Swiss Clinical Quality Management cohort.ResultsThe number of consultations dropped by 52%, whereas the number of remote assessments increased by 129%. The proportion of patients with drug non-compliance slightly increased during the pandemic, the difference reaching statistical significance in axSpA (19.9% vs 13.2% before the pandemic, p=0.003). The proportion of patients with disease flares remained stable (<15%). There was no increase in mean values of the Bath Ankylosing Disease Activity Index, the Rheumatoid Arthritis Disease Activity Index-5 and the Patient Global Assessment in patients with axSpA, RA and PsA, respectively.ConclusionA short interruption of in-person patient–rheumatologist interactions had no major detrimental impact on the disease course of axSpA, RA and PsA as assessed by patient-reported outcomes.

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Changes in Market Share of Biologic and Targeted Synthetic DiseaseModifying Anti-Rheumatic Drugs for Treatment of Rheumatoid Arthritis: Results from the Ontario Best-Practice Research Initiative Database

Current Rheumatology Reviews ◽

10.2174/1573397116666201211130337 ◽

2020 ◽

Vol 16 ◽

Author(s):

Elliot Hepworth ◽

Mohammad Movahedi ◽

Emmanouil Rampakakis ◽

Reza Mirza ◽

Arthur Lau ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Best Practice ◽

Descriptive Analysis ◽

Practice Research ◽

First Line ◽

Biologic Dmards ◽

Research Initiative ◽

Advanced Therapy ◽

Advanced Therapies ◽

Synthetic Dmards

Objective: For patients with Rheumatoid Arthritis (RA) who do not achieve adequate clinical response with combined conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), initiation of advanced therapies such as biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) is recommended. Tumour necrosis factor inhibitors (TNFi) are the oldest, and most commonly used subgroup of advanced therapies. In the last decade, new non-TNFi advanced therapy options have become available. We described the relative use of TNFi vs. non-TNFi in Ontario-based practices from 2008-2017. Methods: Adult patients with RA enrolled in the Ontario Best Practices Research Initiative (OBRI) database who started bDMARDs or tsDMARDs anytime during, or within 30 days prior to enrollment were included. The proportion of patients treated with TNFi vs. non-TNFi agents between 2008 and 2017 was described for: all patients, and those initiating their first bDMARD/tsDMARD. All TNFi therapies are included. Non-TNFi included: Abatacept, Rituximab, Tocilizumab, and Tofacitinib. Results: A total of 1,057 patients were included of whom 72.0% were bDMARD/tsDMARD naïve. In 2008, the relative non-TNFi use was 5.4% in all patients while it was 0% in bDMARD/tsDMARD-naïve patients. By 2017, the proportion of patients using non-TNFi increased to 33.8% among all patients and 33.3% in bDMARD/tsDMARD-naïve patients. Conclusion: This descriptive analysis of data from the OBRI cohort reveals TNFi are still used in the majority of cases, however, there has been an increase in the use of non-TNFi therapies both overall and as first line advanced therapy. This trend towards non-TNFi therapies as first line advanced therapy may be partially explained by the shift in guideline recommendations from TNFi as first-line, to any of the advanced therapeutics.

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Sarilumab: Review of a Second IL-6 Receptor Antagonist Indicated for the Treatment of Rheumatoid Arthritis

Annals of Pharmacotherapy ◽

10.1177/1060028018761599 ◽

2018 ◽

Vol 52 (8) ◽

pp. 780-791 ◽

Cited By ~ 16

Author(s):

Eric G. Boyce ◽

Edward L. Rogan ◽

Deepti Vyas ◽

Neel Prasad ◽

Yvonne Mai

Keyword(s):

Rheumatoid Arthritis ◽

Receptor Antagonist ◽

Data Extraction ◽

Safety Data ◽

Health Assessment ◽

Response Rates ◽

Double Blind ◽

Biologic Dmards ◽

Das28 Remission ◽

Synthetic Dmards

Major Objectives: To review the efficacy, safety, and economics of sarilumab, an interleukin-6 (IL-6) receptor antagonist, in the treatment of rheumatoid arthritis (RA). Data Sources: PubMed (1966 to January 2018), Clinicaltrials.gov (January 2018), and Scopus (1970 to January 2018) were searched using sarilumab, Kevzara, REGN88, and SAR153191. Study Selection and Data Extraction: Human studies published in peer-reviewed publications in English were the primary sources for efficacy and safety. Data Synthesis: Data from randomized, double-blind, controlled, published clinical studies weeks demonstrated statistically significantly higher American College of Rheumatology (ACR) 20, ACR50, and Disease Activity Score-28 (DAS28) remission response rates and improvements in DAS28 and Health Assessment Questionnaire–Disability Index scores for sarilumab monotherapy versus adalimumab monotherapy (P < 0.05) and for sarilumab versus placebo in patients receiving methotrexate or other conventional synthetic disease-modifying antirheumatic drugs (DMARDs); P < 0.05. The ACR20 and ACR50 response rates were, respectively, 56-72% and 35-46% for sarilumab, 58% and 30% for adalimumab, and 33-34% and 15-18% for placebo. DAS28 remission rates were 20-34% for sarilumab, 7% for adalimumab, and 7-10% for placebo. Sarilumab has a higher risk for neutropenia than tocilizumab, the other IL-6 inhibitor, but a lower risk for dyslipidemia, injection site reactions, and gastrointestinal perforation. The acquisition costs of sarilumab are expected to be similar to those of most other biologic DMARDs. Conclusion: Sarilumab is an alternative to biologic DMARDs or targeted synthetic DMARDs in patients with moderate to severely active RA who have not responded adequately to prior conventional synthetic DMARDs or tumor necrosis factor-α inhibitors.

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Response to ‘Correspondence on ‘Impact of the COVID-19 pandemic on the disease course of patients with inflammatory rheumatic diseases: results from the Swiss Clinical Quality Management cohort’ by Ruyssen-Witrand et al

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-219420 ◽

2020 ◽

pp. annrheumdis-2020-219420

Author(s):

Adrian Ciurea ◽

Axel Finckh

Keyword(s):

Quality Management ◽

Rheumatic Diseases ◽

Inflammatory Rheumatic Diseases ◽

Disease Course ◽

Clinical Quality

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POS0517 A LONGITUDINAL STUDY OF SARCOPENIA, LOCOMOTIVE SYNDROME, AND FRAILTY IN PATIENTS WITH RHEUMATOID ARTHRITIS: FROM THE CHIKARA STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1245 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 492.2-492

Author(s):

K. Mandai ◽

M. Tada ◽

Y. Yamada ◽

T. Koike ◽

T. Okano ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Multivariate Logistic Regression Analysis ◽

Locomotive Syndrome ◽

Chi Squared ◽

Higher Doses ◽

Rheumatoid Arthritis Data ◽

Onset Rate ◽

New Onset

Background:Rheumatoid arthritis (RA) patients have a high frequency of sarcopenia, and they commonly have reduced physical function. We previously reported that the prevalence of sarcopenia was 28%, that of frailty was 18.9%, and that of pre-frailty was 38.9% in RA patients1,2, and 13.2% of RA patients developed sarcopenia within a year 3.Objectives:To investigate the risk factors for new onset of sarcopenia, locomotive syndrome, and frailty in patients with RA and the course of each disease.Methods:Two-year follow-up data from the rural group of the prospective, observational CHIKARA study were used. Sarcopenia was diagnosed using the criteria of the Asian Working Group for Sarcopenia 2014, locomotive syndrome was diagnosed using locomotive 5, and frailty was diagnosed using the basic checklist. New onset of the disease over the 2-year follow-up period was studied, excluding cases that had the disease at baseline. Improvement was defined as cases with disease at baseline that no longer met the diagnostic criteria after 2 years. Differences in the characteristics of each disease were tested using the Chi-squared test and the paired t-test.Results:The 81 patients with RA (82.7% female) had mean age 66.9±11.5 years, mean DAS28-ESR 2.9±1.2, methotrexate use in 81.5% (with a dose of 9.9±2.7 mg/week), and glucocorticoid (GC) use in 22.2% (with a dose of 3.1±1.7 mg/week). The baseline prevalence was 44.4% for sarcopenia, 35.8% for locomotive syndrome, and 25.9% for frailty, and the new onset rate was 4.4% for sarcopenia, 15.4% for locomotive syndrome, and 13.3% for frailty. Of the patients with each disease at baseline, 36.1% had sarcopenia, 20.7% had locomotive syndrome, and 33.3% had frailty, and of those with each disease at 2 years, 36.1% had sarcopenia, 20.7% had locomotive syndrome, and 33.3% had frailty. The new onset sarcopenia and locomotive syndrome groups had significantly higher rates of GC use (p=0.036, p=0.007, paired t-test) and significantly higher doses (p=0.01, p=0.001, paired t-test) than the groups without new onset sarcopenia and locomotive syndrome. High baseline disease activity was an independent predictor of new onset of locomotive syndrome on multivariate logistic regression analysis (OR=3.21, p=0.015).Conclusion:The new onset rates at 2 years were 4.4% for sarcopenia, 15.4% for locomotive syndrome, and 13.3% for frailty. In the new onset sarcopenia and locomotive syndrome groups, both GC use and dosage were significantly higher.References:[1]Tada M, et al. Matrix metalloprotease 3 is associated with sarcopenia in rheumatoid arthritis - results from the CHIKARA study. Int J Rheum Dis. 2018 Nov;21(11):1962-1969.[2]Tada M, et al. Correlation between frailty and disease activity in patients with rheumatoid arthritis: Data from the CHIKARA study. Geriatr Gerontol Int. 2019 Dec;19(12):1220-1225.[3]Yamada Y, et al. Glucocorticoid use is an independent risk factor for developing sarcopenia in patients with rheumatoid arthritis: from the CHIKARA study. Clin Rheumatol. 2020 Jun;39(6):1757-1764.Disclosure of Interests:None declared

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AB1119 U9: A NOVEL CLINICALLY ORIENTED ULTRASONOGRAPHIC SCALE AS A USEFUL MARKER FOR MONITORING THERAPEUTIC RESPONSE IN RHEUMATOID ARTHRITIS (MULTI CENTERS STUDY)

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2733 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1848.2-1849

Author(s):

M. A. Mortada ◽

H. Eitta ◽

R. Elmallah ◽

A. Radwan ◽

A. Elsaman

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Clinical Laboratory ◽

Pearson Correlation ◽

Response To Treatment ◽

P Value ◽

Clinical Parameters ◽

Biologic Dmards ◽

Das 28 ◽

Significant Difference

Background:Musculoskeletal Ultrasonography (MSUS) is now a widely used tool for monitoring of rheumatoid arthritis (RA). Although there are many proposed sets of composite scores, a fixed set of joints may not be an ideal tool to assess a disease like RA, which affects many joints and tendons in different presentations. In previous study (1) U9 score was proven to be correlated with disease activity parameters.Objectives:To determine whether US assessment using U9 score is useful for monitoring response to treatment for RA or not?Methods:A prospective, multicenter study were conducted in period from July 2019 to December 2019. All recruited RA patients were subjected to: Disease activity assessment by clinical disease activity indices (CDAI and DAS28 ESR). Functional status assessment by (HAQ) and ultrasonographic assessment using U9 score which include 8 joints (bilateral wrists,2ndMCP,3RDMCP and knees) plus most clinically affected joint or tendon (one joint or one tendon). Most clinically affected joints from 48 joints. Any affected tendons could be choosing. All targeted joints were evaluated according to EULAR guidlines and by EULAR/ OMERACT combined score (0-3). Targeted tendons were scored (0-3).All patients received their treatment (biologic and non biologic DMARDs) according to the decision of the treating physicians. No specific therapy is needed. CDAI and DAS28 ESR, HAQ and U9 score were repeated after 3 months to detect the response to change after receiving the therapy.Results:One hundred and forty patients (23.6% were male) with mean age 39.26±11.30 were recruited from 4 tertiary referral university hospitals.There was a significant difference (<0.001) between the first and second visits as regards clinical, laboratory and ultrasonographic parameters. DAS 28 decreased form (5.29±1.21) to (3.95±0.99), ESR decreased from (42.12±15.24) to (26.84±12.32), HAQ2 improved from (0.652±0.350) to (0.510±0.237) and U9 total US score decreased from (13.56±5.18) to (8.02±4.28).There was significant correlation between U9 ultrasonographic score and clinical parameters at both visits (table 1).Table 1.correlation between U9 ultrasonographic score and clinical parameters.U9 at 1stvisitU9 at 2ndvisitDAS-28Pearson Correlation(P value)0.806<0.0010.790<0.001CDAIPearson Correlation(P value)0.787<0.0010.773<0.001HAQPearson Correlation(P value)0.431<0.0010.317<0.001We found that the most suitable cut-off value of U9 score to predict high disease activity was 11.5 (sensitivity 85.7% and specificity 80.6%), cut off value for moderate disease activity was 5.5(sensitivity 83.2% and specificity 88%) and cut off value for low disease activity was 3.5 (sensitivity of 83.3% and specificity 57.1%). These results are summarized in the following table:Conclusion:U9 ultrasonographic score is very useful method for evaluating the monitoring the response of treatment.References:[1]Mortada, et al. Annals of the Rheumatic Diseases 2019;78:1009.Disclosure of Interests:None declared

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POS0642 THE IMPACT OF AGE ON DISCONTINUATION OF BIOLOGIC DMARDs IN PATIENTS WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3759 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 559.2-560

Author(s):

V. Rivera Teran ◽

S. Sicsik ◽

D. Vega-Morales ◽

F. Irazoque-Palazuelos ◽

D. Miranda ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Adverse Effects ◽

Adverse Events ◽

Cox Regression ◽

Retention Rate ◽

Drug Discontinuation ◽

Discontinuation Rate ◽

Biologic Dmards ◽

Conventional Dmards ◽

The Impact

Background:Rheumatoid arthritis (RA) is the most common autoimmune disease. Older patients treated with biologic DMARDs (bDMARDs) are at a significantly greater risk of adverse effects (AEs) [1]. However, the rate of drug discontinuation because of adverse effects caused by bDMARDs has not differed in elderly compared to younger patients in different registries.Objectives:Determine if drug discontinuation of bDMARDs differs by age in patients with rheumatoid arthritis in the Mexican Adverse Events Registry (BIOBADAMEX).Methods:BIOBADAMEX is a Mexican ongoing cohort of patients using bDMARDs since 2016. In this analysis we included all patients with diagnosis of RA with at least two assessments. Survival on bDMARDs was estimated using Kaplan-Meier analysis. Predictors of discontinuation, including age older than median age in the sample were investigated by Cox regression analyses.Results:Among 743 patients in the registry, 497 had RA diagnosis, from which, 214 had at least two assessments. At baseline, patients had a median (IQR) age of 53.4 (45-61) years old, median disease duration of 10.7 (6-17) months and median DAS28 of 4.7 (3-6). Conventional DMARDS were used by 185 (87%) patients and 94 (44%) patients used corticosteroids. Comorbidities were present in 194 (91%). The most common bDMARDs received at baseline were abatacept 59 (27%), tocilizumab 45(21%), adalimumab 31 (15%) and certolizumab 30 (14%). At the time of analysis, the median bDMARDs treatment duration was 21.0(13-34) months, 128 (59%) had discontinued treatment, 66 for inefficacy, 32 for adverse events and 30 for others. Fig 1 shows discontinuation rate curves in patients younger and older than median age. Cox proportional-hazards demonstrated no significant differences regarding age older than median age (HR 1.1, 95% CI 0.8-1.4, p=0.7), female sex (HR 1.2, 95% CI 0.7-1.9, p=0.44), use of corticosteroids (HR 1.2, 95% CI 0.9-1.6, p=0.20), comorbidities (HR 0.9, 95% 0.6-1.5, p=0.78), DAS28 (HR 0.9, 95% 0.9-1.1, p=0.93) or other factors.Figure 1.Discontinuation rate curves in patients younger and older than median age (< 53.4 and >=53.4 years old)Conclusion:This analysis did not show a role of age on discontinuation of bDMARDs in Mexican RA patients. Further longitudinal analyses will be performed including more patients to assess retention rate of bDMARDs and identify predictive variables of discontinuation in Mexican population.References:[1]Akter R, et al. Can Geriatr J. 2020 May 1;23(2):184-189.[2]Ikari Y, et al. Medicine (Baltimore). 2020 Dec 24;99(52):e23861.Disclosure of Interests:None declared

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