Rheumatoid Arthritis

2014 ◽  
pp. 231-241
Author(s):  
Derrick J. Todd ◽  
Jonathan S. Coblyn
Keyword(s):  
Rheumatoid Arthritis ◽  
Laboratory Tests ◽  
Treatment Options ◽  
Joint Destruction ◽  
Autoimmune Disorder ◽  
Cartilage Destruction ◽  
Pharmacologic Treatment ◽  
Life Threatening ◽  
Disease Modifying ◽  
Over Time

Rheumatoid arthritis (RA) is an idiopathic systemic autoimmune disorder that primarily involves the joints. It causes inflammation of the synovium (synovitis) that can lead to cartilage destruction and bone erosions. Extra-articular manifestations may also occur. The diagnosis of RA is based on a combination of clinical features, laboratory tests, and imaging studies. In recent years, great strides have been made in the pharmacologic treatment of RA, which consists primarily of immunosuppressive or immunomodulatory therapy with disease-modifying antirheumatic drugs (DMARDs). It is important to understand that RA is a heterogeneous disorder: some patients may have a severe, rapidly progressive disease with life-threatening extra-articular symptoms, whereas other patients may have indolent symptoms with little if any joint destruction over time. This point is important when making a diagnosis of RA, and especially when considering treatment options.

scholarly journals Managing Osteoporosis and Joint Damage in Patients with Rheumatoid Arthritis: An Overview

2021 ◽  
Vol 10 (6) ◽  
pp. 1241
Author(s):  
Yoshiya Tanaka
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Damage ◽  
Kinase Inhibitors ◽  
Joint Destruction ◽  
Joint Damage ◽  
Nuclear Factor Κb ◽  
Cartilage Destruction ◽  
Janus Kinase ◽  
Systemic Autoimmune Disease ◽  
And Cartilage

In rheumatoid arthritis, a representative systemic autoimmune disease, immune abnormality and accompanying persistent synovitis cause bone and cartilage destruction and systemic osteoporosis. Biologics targeting tumor necrosis factor, which plays a central role in the inflammatory process, and Janus kinase inhibitors have been introduced in the treatment of rheumatoid arthritis, making clinical remission a realistic treatment goal. These drugs can prevent structural damage to bone and cartilage. In addition, osteoporosis, caused by factors such as menopause, aging, immobility, and glucocorticoid use, can be treated with bisphosphonates and the anti-receptor activator of the nuclear factor-κB ligand antibody. An imbalance in the immune system in rheumatoid arthritis induces an imbalance in bone metabolism. However, osteoporosis and bone and cartilage destruction occur through totally different mechanisms. Understanding the mechanisms underlying osteoporosis and joint destruction in rheumatoid arthritis leads to improved care and the development of new treatments.

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

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 880 ◽  
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.

scholarly journals Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease-modifying antirheumatic drugs (DESIRABLE study): a randomised, double-blind, placebo-controlled phase 3 trial

2019 ◽  
Vol 78 (7) ◽  
pp. 899-907 ◽  
Author(s):  
Tsutomu Takeuchi ◽  
Yoshiya Tanaka ◽  
Satoshi Soen ◽  
Hisashi Yamanaka ◽  
Toshiyuki Yoneda ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Placebo Group ◽  
Structural Damage ◽  
Bone Erosion ◽  
Joint Destruction ◽  
Mineral Density ◽  
Phase 3 ◽  
Double Blind ◽  
The Mean ◽  
Disease Modifying

ObjectiveTo evaluate the efficacy of denosumab in suppressing joint destruction when added to conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy in patients with rheumatoid arthritis (RA).MethodsThis was a multi-centre, randomised, double-blind, parallel-group, placebo-controlled phase 3 study in Japan. Patients with RA aged ≥20 years receiving csDMARDs were randomly assigned (1:1:1) to denosumab 60 mg every 3 months (Q3M), denosumab 60 mg every 6 months (Q6M) or placebo. The change in the modified total Sharp score (mTSS) and effect on bone mineral density (BMD) at 12 months was evaluated.ResultsIn total, 654 patients received the trial drugs. Denosumab groups showed significantly less progression of joint destruction. The mean changes in the mTSS at 12 months were 1.49 (95% CI 0.99 to 1.99) in the placebo group, 0.99 (95% CI 0.49 to 1.49) in the Q6M group (p=0.0235) and 0.72 (95% CI 0.41 to 1.03) in the Q3M group (p=0.0055). The mean changes in bone erosion score were 0.98 (95% CI 0.65 to 1.31) in the placebo group, 0.51 (95% CI 0.22 to 0.80) in the Q6M group (p=0.0104) and 0.22 (95% CI 0.09 to 0.34) in the Q3M group (p=0.0001). No significant between-group difference was observed in the joint space narrowing score. The per cent change in lumbar spine (L1–L4) BMD in the placebo, Q6M and Q3M groups were −1.03%, 3.99% (p<0.0001) and 4.88% (p<0.0001). No major differences were observed among safety profiles.ConclusionsDenosumab inhibits the progression of joint destruction, increases BMD and is well tolerated in patients with RA taking csDMARD.

Remission achieved after 2 years treatment with low-dose prednisolone in addition to disease-modifying anti-rheumatic drugs in early rheumatoid arthritis is associated with reduced joint destruction still present after 4 years: an open 2-year continuation study

2008 ◽  
Vol 68 (4) ◽  
pp. 508-513 ◽  
Author(s):  
I Hafström ◽  
K Albertsson ◽  
A Boonen ◽  
D van der Heijde ◽  
R Landewé ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Low Dose ◽  
Joint Destruction ◽  
Joint Space ◽  
Mineral Density ◽  
Scoring Method ◽  
Sustained Effect ◽  
Radiological Damage ◽  
Disease Modifying ◽  
Hands And Feet

Objective:To evaluate if remission induced by low-dose prednisolone during the first 2 years of rheumatoid arthritis (RA) in the BARFOT glucocorticoid (GC) study had a sustained effect on radiological damage for a total of 4 years.Methods:A total of 150 of 211 eligible patients with RA who had been randomised to the 7.5 mg prednisolone group (P) or no prednisolone group (NoP) in addition to the initial disease-modifying antirheumatic drugs were included. Radiographs of hands and feet were scored using the Sharp–van der Heijde scoring method. A patient was considered to be in remission if the 28-joint count disease activity score was <2.6.Results:Mean (SD) age was 53 (14) and 57 (12) years for the patients in the P and NoP groups, respectively. 64% were female, 64% rheumatoid factor positive, and disease duration at baseline was 6 months. At 2 years the proportion of patients in remission in the P and NoP groups was 55 vs 30%, p = 0.003. Longitudinal analysis showed that over the entire course of the disease, patients on prednisolone had a higher probability of being in remission. Patients in remission at 2 years, compared with those not in remission, had significantly lower total Sharp score, erosion score and joint space narrowing score at 2 and 4 years. The changes in bone mineral density during the 4 years did not differ between those in remission and those with active disease, and were similar in the two treatment groups.Conclusions:Prednisolone 7.5 mg daily in addition to disease-modifying anti-rheumatic drugs increases the rate of remission in patients with early RA, which has a beneficial and sustained effect on radiological damage.

scholarly journals SAT0146 INHIBITION OF RADIOGRAPHIC PROGRESSION BY IGURATINOD IN 116 JAPANESE RHEUMATOID ARTHIRITIS PATIENTS DESPITE CONVENTIONAL SYNTHETIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS THERAPY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1011.2-1012
Author(s):  
K. Katayama ◽  
T. Okubo ◽  
K. Yujiro ◽  
R. Fukai ◽  
T. Sato ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Active Rheumatoid Arthritis ◽  
Disease Duration ◽  
Radiographic Progression ◽  
Controlled Trial ◽  
Joint Destruction ◽  
Inhibitory Effects ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Disease Modifying

Background:Japanese double-blind clinical practice studies of Iguratimod (IGU) for active rheumatoid arthritis (RA) patients indicated an early and sustained efficacy as a new conventional synthetic disease-modyfing anti-rheumatic drugs (csDMARDs) [1] as well as the safety of the treatment[2]. IGU also inhibit activation of NFkB and production of RANKL, indicating strong inhibiting activity against bone destruction. However, studies focused on the inhibitory effects of joint destruction by IGU has been poorly documented in clinical practice (3).Objectives:To evaluate inhibitory effect during 1 year by additional IGU therapy in 116 RA patients despite csDMARDs therapy.Methods:Inhibitory effects of joint damage were evaluated by modified total Sharp scoring (mTSS) at baseline and 1 year after IGU prescription. RA activity was measured by DAS28-ESR.Results:The subjects were 116 cases, 30 male, age 63.2 yrs, disease duration 93.7 months. MTX was used weekly (84 cases, 72.4%), and cs DMARDs were used as BUC 43 cases, SASP 13 cases, TAC 5 cases, and LEF 1 cases. bDMARDs were used even in 8 cases, and steroids were used in 3.9 mg (70 cases, 60.3 %). Complications were observed in 70 cases (60.3%). DAS28-ESR were significantly improved from 4.29 (baseline) to 3.65 (6 months), 3.68 (12 months), respectively (P<0.0001). As shown in Figure 1, joint destruction measured by mTSS was significantly suppressed from 7.74 to 0.57 at 1 year (P<0.0001). 70.6% of patients satisfied structural remission (ΔmTSS≤0.5). Clinically relevant radiographic progression (CRRP)(mTSS>3) was observed in 10 cases (8.6%), and rapid radiographic progression(RRP) (mTSS≥5) was observed in 2 cases (1.6%). Adverse events were observed in 26 cases (22.4 %).To investigate prognostic factor for CRRP, clinical data in baseline, 6, 12 months between ten patients with CRRP and 82 patients with structural remission were compared. As shown in Table 1, longer disease duration, more SJC (P<0.05), High CRP level(P<0.005) were prognostic for CRRP in IGU treated patients.Conclusion:Iguratimod suppressed not only clinical activities but also joint destruction in RA patients resistant to csDMARDs therapy.Table 1. Prognostic factor for CRRPReferences:[1]Ishiguro N, Yamamoto K, Katayama K et al. Concomitant iguratimod therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate a randomized, double-blind, placebo-controlled trial. Mod Rheumatol. 2013;23(3):430-9[2]Hara M, Ishiguro N, Katayama K et al. Safety and efficacy of combination therapy of iguratimod with methotrexate for patients with active rheumatoid arthritis with an inadequate response to methotrexate: an open-level extension of a randomized, double-blind, placebo-controlled trial. Mod Rheumatol. 2014;24(3):410–8.[3]Ishikawa K, Ishikawa J.Iguratimod, a synthetic disease modifying anti-rheumatic drug inhibiting the activation of NF-jB and production of RANKL: Its efficacy, radiographic changes,safety and predictors over two years’ treatment for Japanese rheumatoid arthritis patients. Mod.Rheumatol.2019,29(3), 418–429.Disclosure of Interests:None declared

scholarly journals Research Progress of Therapeutic Enzymes and Their Derivatives: Based on Herbal Medicinal Products in Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Ming Cai ◽  
Wei-Jian Ni ◽  
Lan Han ◽  
Wei-Dong Chen ◽  
Dai-Yin Peng
Keyword(s):  
Rheumatoid Arthritis ◽  
Basic Research ◽  
Autoimmune Disorder ◽  
Cartilage Destruction ◽  
Research Progress ◽  
Medicinal Products ◽  
Herbal Medicinal Products ◽  
Wide Range ◽  
Herbal Medicinal ◽  
Anti Inflammatory

Rheumatoid arthritis (RA) acts as one of the most common, agnogenic and chronic inflammatory-autoimmune disorder which is characterized by persistent synovitis, cartilage destruction, and joint deformities, leads to a wide range of disabilities, and increased mortality, thus imposing enormous burdens. Several drugs with anti-inflammatory and immunomodulatory properties such as celecoxib, diclofenac and methotrexate are being selected as conventional drugs in the allopathic system of medicine for the treatment of RA in clinic. However, there are some serious side effects more or less when using these drugs because of their short poor bioavailability and biological half-life for a long time. These shortcomings greatly promote the exploration and application of new low- or no-toxicity drugs for treating the RA. Meanwhile, a growing number of studies demonstrate that several herbs present certain anti-inflammatory and anti-arthritic activities through different enzymes and their derivatives, which indicate that they are promising therapeutic strategies when targeting these mediators based on herbal medicinal products in RA research. This review article summarizes the roles of the main enzymes and their derivatives during the pathogenesis of RA, and clearly clarifies the explicit and potential targeted actions of herbal medicinal products that have anti-RA activity. Our review provides timely and critical reference for the scientific rationale use of herbal medicinal products, with the increasing basic research and clinical application of herbal medicinal products by patients with RA.

scholarly journals Iguratimod, A Synthetic Disease Modifying Anti- Rheumatic Drug (Sdmard), and Various Dmards Suppress Joint Destruction. The Pathophysiological Mechanisms of the Inhibition of Bone/Cartilage Destruction

2018 ◽  
Vol 4 (1) ◽  
pp. 121-131
Author(s):  
Koichiro Ishikawa ◽  
Junichiro Ishikawa
Keyword(s):  
Joint Destruction ◽  
Cartilage Destruction ◽  
Sodium Aurothiomalate ◽  
Radiographic Outcomes ◽  
Smallest Detectable Change ◽  
Receptor Activator ◽  
Daily Dose ◽  
Suppression Mechanism ◽  
Disease Modifying ◽  
Rheumatic Drug

Objective: To elucidate the radiographic outcomes for rheumatoid arthritis (RA) patients using the synthetic disease-modifying antirheumatic drug (sDMARD) Iguratimod (IGU) and other DMARDs including injectable sodium aurothiomalate, bucillamine, salazosulphapyridine, infliximab, etanercept, tocilizumab and/or abatacept.Patients and Methods: 213 patients were enrolled in this study. Total Genant-modified Sharp scores (GSS) of hands/wrists and feet at baseline and at week 104 were calculated in 31 RA patients treated with a daily dose of 25 mg or 50 mg for 104 weeks.Results: Total GSS of 31 patients at week 104 showed no progression (total GSS  <= 0.84: the smallest detectable change) in 16 (52%) patients with a mean score reduction (95% CI) of-4.3 (-8.1 ~ -0.5) (p < 0.05).Conclusion: Treatment with the sDMARD, IGU showed no radiographic progression in 16 (52%) RA patients at week 104. Concerning the suppression mechanism of joint destruction by IGU and other DMARDs, we speculate that DMARDs prevent bone/cartilage destruction by inhibiting the receptor activator of nuclear factor-kappa B (NF- kB) lig and (RANKL) and through other antirheumatic actions.

scholarly journals Reconsidering the Role of Melatonin in Rheumatoid Arthritis

2020 ◽  
Vol 21 (8) ◽  
pp. 2877 ◽  
Author(s):  
Iona J. MacDonald ◽  
Chien-Chung Huang ◽  
Shan-Chi Liu ◽  
Chih-Hsin Tang
Keyword(s):  
Rheumatoid Arthritis ◽  
Clock Gene ◽  
Joint Destruction ◽  
Preclinical Models ◽  
Synovial Proliferation ◽  
Janus Kinases ◽  
Clock Gene Expression ◽  
Joint Disorder ◽  
Over Time

Rheumatoid arthritis (RA) is an inflammatory joint disorder characterized by synovial proliferation and inflammation, with eventual joint destruction if inadequately treated. Modern therapies approved for RA target the proinflammatory cytokines or Janus kinases that mediate the initiation and progression of the disease. However, these agents fail to benefit all patients with RA, and many lose therapeutic responsiveness over time. More effective or adjuvant treatments are needed. Melatonin has shown beneficial activity in several animal models and clinical trials of inflammatory autoimmune diseases, but the role of melatonin is controversial in RA. Some research suggests that melatonin enhances proinflammatory activities and thus promotes disease activity in RA, while other work has documented substantial anti-inflammatory and immunoregulatory properties of melatonin in preclinical models of arthritis. In addition, disturbance of the circadian rhythm is associated with RA development and melatonin has been found to affect clock gene expression in joints of RA. This review summarizes current understanding about the immunopathogenic characteristics of melatonin in RA disease. Comprehensive consideration is required by clinical rheumatologists to balance the contradictory effects.

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