Response to: Correspondence on “Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis” by Sparks et al

Abstract Background In Norway, an annual tender system for the prescription of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) has been used since 2007. This study aimed to explore annual b/tsDMARDs costs and disease outcomes in Norwegian rheumatoid arthritis (RA) patients between 2010 and 2019 under the influence of the tender system. Methods RA patients monitored in ordinary clinical practice were recruited from 10 Norwegian centers. Data files from each center for each year were collected to explore demographics, disease outcomes, and the prescribed treatment. The cost of b/tsDMARDs was calculated based on the drug price given in the annual tender process. Results The number of registered RA patients increased from 4909 in 2010 to 9335 in 2019. The percentage of patients receiving a b/tsDMARD was 39% in 2010 and 45% in 2019. The proportion of b/tsDMARDs treated patients achieving DAS28 remission increased from 42 to 67%. The estimated mean annual cost to treat a patient on b/tsDMARDs fell by 47%, from 13.1 thousand euros (EUR) in 2010 to 6.9 thousand EUR in 2019. The mean annual cost to treat b/tsDMARDs naïve patients was reduced by 75% (13.0 thousand EUR in 2010 and 3.2 thousand EUR in 2019). Conclusions In the period 2010–2019, b/tsDMARD treatment costs for Norwegian RA patients were significantly reduced, whereas DAS28 remission rates increased. Our data may indicate that the health authorities’ intention to reduce treatment costs by implementing a tender system has been successful.

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Rheumatoid arthritis: problems of treatment at the present stage

Modern Rheumatology Journal ◽

10.14412/1996-7012-2018-4-65-70 ◽

2018 ◽

Vol 12 (4) ◽

pp. 65-70

Author(s):

N. V. Chichasova

Keyword(s):

Rheumatoid Arthritis ◽

Biologic Agents ◽

Control Treatment ◽

Treat To Target ◽

Present Stage ◽

Disease Modifying Antirheumatic Drugs ◽

Antirheumatic Drugs ◽

Synthetic Dmards ◽

Disease Modifying ◽

Set Up

The possibilities of rheumatoid arthritis therapy have been significantly expanded today. In addition to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologic agents (BAs), and a targeted synthetic DMARD, a control treatment strategy has been put into practice.The paper demonstrates successes in the early prescription of csDMARD and the implementation of treat-to-target principles – to achieve the goal after 6 months in 50% of patients receiving subcutaneous methotrexate and 45% of those using a Leflunomide generic. During this therapy, there is a lower need for BAs and targeted synthetic DMARDs. The priority problem is to train general practitioners in methods for the early detection of RA and to set up schools for these patients.

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

Rheumatology ◽

10.1093/rheumatology/kev019 ◽

2015 ◽

Vol 54 (9) ◽

pp. 1664-1672 ◽

Cited By ~ 42

Author(s):

Cem Gabay ◽

Myriam Riek ◽

Almut Scherer ◽

Axel Finckh

Keyword(s):

Rheumatoid Arthritis ◽

Quality Management ◽

Biologic Dmards ◽

Clinical Quality ◽

Synthetic Dmards ◽

Rheumatoid Arthritis Data

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Periodontitis Severity Affects the Clinical Response to Biological Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis: A 1-Year Follow-up Study

Modern Rheumatology ◽

10.1093/mr/roab121 ◽

2021 ◽

Author(s):

Tetsuo Kobayashi ◽

Satoshi Ito ◽

Akira Murasawa ◽

Hajime Ishikawa ◽

Koichi Tabeta

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Response ◽

Activity Index ◽

Disease Activity Index ◽

Positive Association ◽

Disease Modifying Antirheumatic Drugs ◽

Antirheumatic Drugs ◽

Case Definitions ◽

Synthetic Dmards ◽

Disease Modifying

ABSTRACT Objectives To assess whether periodontitis severity affects the clinical response to biological disease-modifying antirheumatic drugs (bDMARDs) for 1 year in rheumatoid arthritis (RA) patients. Methods Data were collected from 50 RA patients who had received corticosteroids, conventional synthetic DMARDs, or non-steroidal anti-inflammatory drugs before (baseline) and after 1 year of bDMARD therapy in a retrospective study. Rheumatologic conditions were compared between the two periodontitis severity groups according to the periodontal inflamed surface area (PISA) or Centers for Disease Control Prevention (CDC)/ American Academy of Periodontology (AAP) case definitions Results Twenty-eight patients with no or mild periodontitis showed significantly greater decreases in changes in Clinical Disease Activity Index (CDAI) and tender and swollen joint count in comparison to 22 patients with moderate and severe periodontitis (p = 0.02, p = 0.01, and p = 0.03). Both bivariate and multivariate analyses revealed a significantly positive association between the baseline CDC/AAP definitions and CDAI changes (p = 0.005 and p = 0.0038). However, rheumatologic conditions were comparable between 25 patients each in the low and high PISA groups. Conclusions Baseline periodontitis severity according to the CDC/AAP definitions is associated with the clinical response to bDMARDs for 1 year in RA patients.

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Small Molecule Inhibitors in the Treatment of Rheumatoid Arthritis and Beyond: Latest Updates and Potential Strategy for Fighting COVID-19

Cells ◽

10.3390/cells9081876 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1876

Author(s):

Magdalena Massalska ◽

Wlodzimierz Maslinski ◽

Marzena Ciechomska

Keyword(s):

Rheumatoid Arthritis ◽

Small Molecule ◽

Viral Entry ◽

Small Molecule Inhibitors ◽

Large Family ◽

Downstream Signaling ◽

Wide Range ◽

Synthetic Dmards ◽

Potential Strategy ◽

Inflammatory Molecules

The development of biological disease-modifying antirheumatic drugs (bDMARDs) and target synthetic DMARDs (tsDMARDs), also known as small molecule inhibitors, represent a breakthrough in rheumatoid arthritis (RA) treatment. The tsDMARDs are a large family of small molecules targeting mostly the several types of kinases, which are essential in downstream signaling of pro-inflammatory molecules. This review highlights current challenges associated with the treatment of RA using small molecule inhibitors targeting intracellular JAKs/MAPKs/NF-κB/SYK-BTK signaling pathways. Indeed, we have provided the latest update on development of small molecule inhibitors, their clinical efficacy and safety as a strategy for RA treatment. On the other hand, we have highlighted the risk and adverse effects of tsDMARDs administration including, among others, infections and thromboembolism. Therefore, performance of blood tests or viral infection screening should be recommended before the tsDMARDs administration. Interestingly, recent events of SARS-CoV-2 outbreak have demonstrated the potential use of small molecule inhibitors not only in RA treatment, but also in fighting COVID-19 via blocking the viral entry, preventing of hyperimmune activation and reducing cytokine storm. Thus, small molecule inhibitors, targeting wide range of pro-inflammatory singling pathways, may find wider implications not only for the management of RA but also in the controlling of COVID-19.

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Low rates of radiographic progression of structural joint damage over 2 years of baricitinib treatment in patients with rheumatoid arthritis

RMD Open ◽

10.1136/rmdopen-2019-000898 ◽

2019 ◽

Vol 5 (1) ◽

pp. e000898 ◽

Cited By ~ 5

Author(s):

Desirée van der Heijde ◽

Michael Schiff ◽

Yoshiya Tanaka ◽

Li Xie ◽

Gabriella Meszaros ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Combination Therapy ◽

Radiographic Progression ◽

Joint Damage ◽

Phase Iii ◽

Inadequate Response ◽

Smallest Detectable Change ◽

Structural Joint ◽

Synthetic Dmards ◽

Modified Total Sharp Score

ObjectivesTo evaluate radiographic progression of structural joint damage over 2 years in patients with rheumatoid arthritis from baricitinib clinical trials who were disease-modifying antirheumatic drug (DMARD)–naïve or had an inadequate response to conventional synthetic DMARDs (csDMARD-IR).MethodsPatients had completed one of three phase III studies and entered a long-term extension (LTE) study, continuing on the same baricitinib dose as at originating study completion. At 52 weeks, DMARD-naïve patients receiving methotrexate (MTX) or combination therapy (baricitinib 4 mg+MTX) were switched to baricitinib 4 mg monotherapy (±MTX per investigator opinion); MTX-IR patients receiving adalimumab were switched to baricitinib 4 mg on background MTX. At 24 weeks, csDMARD-IR patients receiving placebo were switched to baricitinib 4 mg on background csDMARD. Radiographs at baseline, year 1 and year 2 were scored using the van der Heijde modified Total Sharp Score. Linear extrapolation was used for missing data.ResultsOf 2573 randomised patients, 2125 (82.6%) entered the LTE, of whom 1893 (89.1%) entered this analysis. At year 2, progression was significantly lower with initial baricitinib (monotherapy or combination therapy) versus initial MTX in DMARD-naïve patients (proportion with non-progression defined by ≤smallest detectable change (SDC): 87.3% baricitinib 4 mg+MTX; 70.6% MTX; p≤ 0.001). In MTX-IR patients, progression with initial baricitinib was significantly lower than with initial placebo and similar to initial adalimumab (≤SDC: 82.7% baricitinib 4 mg; 83.5% adalimumab; 70.6% placebo; p≤0.001). In csDMARD-IR patients, significant benefit was seen with baricitinib 4 mg (≤SDC: 87.2% vs 73.2% placebo; p≤0.01).ConclusionsTreatment with once-daily baricitinib resulted in low rates of radiographic progression for up to 2 years.

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Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis

Cells ◽

10.3390/cells9040880 ◽

2020 ◽

Vol 9 (4) ◽

pp. 880 ◽

Cited By ~ 10

Author(s):

Yen-Ju Lin ◽

Martina Anzaghe ◽

Stefan Schülke

Keyword(s):

Rheumatoid Arthritis ◽

Side Effects ◽

Bone Erosion ◽

Treatment Options ◽

Joint Damage ◽

Cartilage Destruction ◽

Biologic Dmards ◽

Clinical Benefits ◽

Synthetic Dmards ◽

Inability To Work

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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