scholarly journals Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jie Huang ◽  
Xuekun Fu ◽  
Xinxin Chen ◽  
Zheng Li ◽  
Yuhong Huang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Targets ◽  
New Drugs ◽  
Joint Disease ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Sustained Development ◽  
Epigenetic Regulators ◽  
Disease Modifying ◽  
Hands And Feet

Rheumatoid arthritis (RA) is a systemic poly-articular chronic autoimmune joint disease that mainly damages the hands and feet, which affects 0.5% to 1.0% of the population worldwide. With the sustained development of disease-modifying antirheumatic drugs (DMARDs), significant success has been achieved for preventing and relieving disease activity in RA patients. Unfortunately, some patients still show limited response to DMARDs, which puts forward new requirements for special targets and novel therapies. Understanding the pathogenetic roles of the various molecules in RA could facilitate discovery of potential therapeutic targets and approaches. In this review, both existing and emerging targets, including the proteins, small molecular metabolites, and epigenetic regulators related to RA, are discussed, with a focus on the mechanisms that result in inflammation and the development of new drugs for blocking the various modulators in RA.

Safety and Effectiveness of 6 Months’ Etanercept Monotherapy and Combination Therapy in Japanese Patients with Rheumatoid Arthritis: Effect of Concomitant Disease-modifying Antirheumatic Drugs

2013 ◽  
Vol 40 (10) ◽  
pp. 1658-1668 ◽  
Author(s):  
Takao Koike ◽  
Masayoshi Harigai ◽  
Shigeko Inokuma ◽  
Naoki Ishiguro ◽  
Junnosuke Ryu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Remission Rate ◽  
Previous Treatment ◽  
Japanese Patients ◽  
Joint Disease ◽  
Concomitant Disease ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Postmarketing Surveillance Study ◽  
Disease Modifying

Objective.To assess real-world safety, tolerability, and effectiveness of etanercept monotherapy, etanercept plus methotrexate (MTX), or etanercept plus other disease-modifying antirheumatic drugs (DMARD) in Japanese patients with active rheumatoid arthritis (RA) despite previous treatment with DMARD.Methods.In this 24-week, all-cases postmarketing surveillance study, adverse events (AE) were coded using the Medical Dictionary for Regulatory Activities. Effectiveness was assessed every 4 weeks using the 28-joint Disease Activity Score and the European League Against Rheumatism response criteria.Results.Of 13,861 patients (81% women) in the analysis, 3616, 2506, and 7739, respectively, were classified into etanercept monotherapy (ETN-mono), etanercept plus DMARD other than MTX (ETN + DMARD), and etanercept plus MTX (ETN + MTX) groups. Rates of AE and serious AE (SAE) in the ETN + MTX group were lower than in other groups. Risk of SAE or serious infections was not significantly increased with higher versus lower MTX doses at baseline or with concomitant use of salazosulfapyridine or bucillamine in ETN + DMARD versus ETN-mono groups. A greater likelihood of achieving clinical remission was seen with ETN + MTX versus ETN-mono (OR 1.36; 95% CI, 1.16–1.60; p < 0.001). Higher MTX dose at baseline was associated with a higher remission rate (> 8 mg vs 0 to ≤ 4 mg, OR 1.47, 95% CI 1.07–2.00, p = 0.016; 6 to ≤ 8 mg vs 0 to ≤ 4 mg, OR 1.27, 95% CI 1.01–1.60, p = 0.038).Conclusion.Combination therapies with etanercept plus MTX or other DMARD were reasonably well tolerated, and ETN + MTX at higher doses was more effective than ETN-mono in Japanese patients with RA.

scholarly journals Safety of Rituximab in Combination with Other Biologic Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis: An Open-label Study

2013 ◽  
Vol 40 (5) ◽  
pp. 599-604 ◽  
Author(s):  
William F.C. Rigby ◽  
Philip J. Mease ◽  
Ewa Olech ◽  
Mark Ashby ◽  
Swati Tole
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Disease ◽  
Inadequate Response ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Link Type ◽  
Disease Modifying

Objective.To characterize the safety of rituximab (RTX) in combination with biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA).Methods.We did an open-label study of the safety and efficacy of RTX in adult patients with active RA and an inadequate response to ≥ 1 biologic for ≥ 12 weeks (stable dose ≥ 4 weeks). RTX (2 × 500 mg) was added to patients’ current biologic and nonbiologic DMARD treatment. After 24 weeks, patients with 28-joint Disease Activity Score ≥ 2.6 were eligible for RTX retreatment. The primary endpoint was the proportion of patients developing a serious adverse event (SAE) within 24 weeks of initiating RTX.Results.Patients (n = 176) received RTX with 18 different biologic/DMARD combinations. Adalimumab alone (n = 46; 26.1%) or etanercept alone (n = 37; 21.0%) plus RTX were the most common combinations. Overall, 90.9% and 76.1% of patients completed 24 and 48 weeks, respectively; 147 patients (83.5%) received a second course of RTX. Over 24 weeks, 9.1% of patients reported SAE (24.3 events/100 patient-yrs, 95% CI 15.5–38.1). The SAE rate was similar over 48 weeks (22.4 events/100 patient-yrs, 95% CI 15.9–31.5). Four serious infections were reported over 48 weeks (2.7 events/100 patient-yrs, 95% CI 1.0–7.2). No SAE occurred within 24 h of any RTX infusion. Efficacy responses improved numerically at Week 48 compared with Week 24.Conclusion.The overall safety profile of RTX in combination with 1 other biologic was consistent with that previously reported for RTX plus methotrexate or other nonbiologic DMARD. (Clinicaltrials.govNCT00443651)

scholarly journals Two-year Efficacy and Safety of Subcutaneous Tocilizumab in Combination with Disease-modifying Antirheumatic Drugs Including Escalation to Weekly Dosing in Rheumatoid Arthritis

2017 ◽  
Vol 45 (4) ◽  
pp. 456-464 ◽  
Author(s):  
Alan Kivitz ◽  
Ewa Olech ◽  
Michael A. Borofsky ◽  
Beatriz Zazueta ◽  
Federico Navarro-Sarabia ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Joint Disease ◽  
Published Data ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Serious Adverse Events ◽  
Disease Modifying

Objective.To evaluate the longterm efficacy and safety of subcutaneous tocilizumab (TCZ-SC) every 2 weeks (q2w) over 2 years in patients with rheumatoid arthritis who have an inadequate response to disease-modifying antirheumatic drugs (DMARD).Methods.Patients (n = 656) were randomized 2:1 to TCZ-SC 162 mg q2w or placebo-SC q2w plus DMARD. After a 24-week double-blind period, patients (n = 457) were rerandomized to open-label TCZ-SC q2w by means of prefilled syringe or autoinjector. Escape therapy with weekly TCZ-SC was available for patients with inadequate efficacy from Week 12. Maintenance of response and safety to 2 years was assessed. Analyses used nonresponder imputation.Results.The American College of Rheumatology (ACR) 20 response after TCZ-SC was maintained beyond Week 24 and was > 70% at each timepoint. ACR50/70, 28-joint Disease Activity Score remission, and ≥ 0.30 decrease from baseline in the Health Assessment Questionnaire–Disability Index response rates were also maintained after Week 24 in the TCZ-SC arm (≥ 50%, > 25%,> 32% and > 56%, respectively). Following escape for inadequate efficacy, many patients achieved ACR20 at the end of the study, 35% after escape from TCZ-SC, and 63% from placebo. The rates of serious adverse events [(11.20/100 patient-years (PY)] including serious infections (3.25/100 PY) were stable through Week 96. No association between anti-TCZ antibody development and loss of efficacy or adverse events was observed.Conclusion.Efficacy and safety of TCZ-SC q2w was maintained up to 2 years and remained comparable with previously published data for intravenous TCZ. Dose escalation to weekly TCZ-SC was associated with ACR responses in prior nonresponders and was well tolerated.

scholarly journals FRI0526 THE INCIDENCE, PREVALENCE AND MEDICATION USE OF RHEUMATOID ARTHRITIS AMONG KOREAN WOMEN IN CHILDBEARING YEARS: A NATIONWIDE POPULATION-BASED STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 862.2-863
Author(s):  
M. K. Chung ◽  
J. S. Park ◽  
H. S. Lim ◽  
C. H. Lee ◽  
J. Lee
Keyword(s):  
Rheumatoid Arthritis ◽  
Lupus Erythematosus ◽  
Medication Use ◽  
Population Based ◽  
Korean Women ◽  
Childbearing Age ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Disease Modifying ◽  
Incidence Prevalence

Background:Rheumatoid arthritis (RA) predominantly affects women and has a significant impact on childbearing. Several population-based studies identifying incidence, prevalence, and medication use of RA have been reported, yet epidemiological studies focusing on women with RA in childbearing years are missing.Objectives:We aimed to identify the incidence, prevalence and medication use of RA among Korean women in childbearing years.Methods:From National Health Insurance Service (NHIS) data (2009-2016), containing inpatient and outpatient claim information for approximately 97% of the Korean population, we identified 9,217,139 women aged between 20-44 years. Incidence and prevalence of RA in the specific sociodemographic group of women in childbearing age were analyzed, and the prevalence of medication prescription were compared between women with RA and controls without rheumatic diseases such as RA, systemic lupus erythematosus, and ankylosing spondylitis. Individuals with RA were defined by the presence of International Classification of Disease, 10th revision code, M05. The medication use was defined as receiving > 90days prescriptions of NSAIDs, corticosteroids (CSs), and conventional synthetic (cs) disease modifying antirheumatic drugs (DMARDs) or > 1day prescription of biologic (b) DMARDs.Results:Total 24,590 women with RA were identified. The average incidence of RA during 2011-2016 among women in childbearing years was 24.1/100,000 person-years (PYs) (95% CI 20.91-27.31) with a yearly increase from 20.99/100,000 PYs in 2011 to 28.38/100,000 PYs in 2016. The average prevalence of RA during 2009-2016 among women in childbearing years was 105.2/100,000 PYs (95% CI 99.0-111.5) with a minimum of 95.7/100,000 PYs in 2009 and a maximum of 110.5/100,000 PYs in 2016. There were increasing trends in both incidence and prevalence of RA according to age among women in childbearing years peaking in the age group of 40-44 years. The prescriptions of NSAIDs, CSs, csDMARDs and bDMARDs were more frequent in women with RA than controls (NSAIDs; 94.21% vs 21.79%, CSs; 83.65% vs 4.28%, csDMARDs; 91.23% vs 0.41%, bDMARDs; 0.11% vs 0%, p<0.001).Conclusion:The incidence and prevalence of RA are high among Korean women in childbearing years, and medication use was significantly more frequent in this specific population than controls. High disease burden is imposed upon women in childbearing years.References:[1] Won S, Cho SK, Kim D, Han M, Lee J, Jang EJ, Sung YK, Bae SC: Update on the prevalence and incidence of rheumatoid arthritis in Korea and an analysis of medical care and drug utilization. Rheumatol Int 2018, 38(4):649-656.[2] Smeele HTW, Dolhain R: Current perspectives on fertility, pregnancy and childbirth in patients with Rheumatoid Arthritis. Seminars in arthritis and rheumatism 2019, 49(3s):S32-s35.Table 1.Medication use among women with RA and controls in childbearing age between 20-44 years during 2009-2016Control(n=155,486)RA(n=23,756)n(%)n(%)PNSAIDs33,887(21.79)22,380(94.21)<.0001Steroids6,653(4.28)19,871(83.65)<.0001csDMARDs634(0.41)21,673(91.23)<.0001bDMARDs0(0.00)27(0.11)<.0001RA, rheumatoid arthritis; NSAID, non-steroidal anti-inflammatory drug; cs, conventional synthetic; b, biologic; DMARDs, disease modifying antirheumatic drugsDisclosure of Interests:None declared

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