scholarly journals Recommendations of the Brazilian Society of Rheumatology for the use of JAK inhibitors in the management of rheumatoid arthritis

2021 ◽  
Vol 61 (1) ◽  
Author(s):  
Karina Rossi Bonfiglioli ◽  
Licia Maria Henrique da Mota ◽  
Ana Cristina de Medeiros Ribeiro ◽  
Adriana Maria Kakehasi ◽  
Ieda Maria Magalhães Laurindo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Intracellular Signaling ◽  
Treatment Algorithm ◽  
Efficacy And Safety ◽  
Jak Inhibitors ◽  
Janus Kinases ◽  
Low Disease Activity ◽  
Brazilian Society ◽  
Systemic Inflammatory Disease

AbstractRheumatoid arthritis (RA) is a chronic and autoimmune systemic inflammatory disease that can cause irreversible joint deformities, with increased morbidity and mortality and a significant impact on the quality of life of the affected individual. The main objective of RA treatment is to achieve sustained clinical remission or low disease activity. However, up to 40% of patients do not respond to available treatments, including bDMARDs. New therapeutic targets for RA are emerging, such as Janus kinases (JAKs). These are essential for intracellular signaling (via JAK-STAT) in response to many cytokines involved in RA immunopathogenesis. JAK inhibitors (JAKi) have established themselves as a highly effective treatment, gaining increasing space in the therapeutic arsenal for the treatment of RA. The current recommendations aim to present a review of the main aspects related to the efficacy and safety of JAKis in RA patients, and to update the recommendations and treatment algorithm proposed by the Brazilian Society of Rheumatology in 2017.

scholarly journals AB0135 A VERY EARLY CLINICAL RESPONSE TO TOFACITINIB IS ASSOCIATED WITH LOW RHEUMATOID ARTHRITIS ACTIVITY AFTER 3 AND 6 MONTHS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1095.3-1096
Author(s):  
A. Karateev ◽  
A. Lila ◽  
E. Nasonov ◽  
V. Mazurov ◽  
D. Chakieva ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Response ◽  
Central Sensitization ◽  
Intracellular Signaling ◽  
Pain Reduction ◽  
Pain Severity ◽  
Jak Inhibitors ◽  
Significant Pain ◽  
Number Of Patients ◽  
Days Of Therapy

Background:JAK inhibitors block intracellular signaling pathways responsible for the synthesis of cytokines and mediators involved in the development of chronic pain and central sensitization (CS). This determines a very rapid clinical response to JAK inhibitors. However, it is not clear how the significant pain reduction in the first weeks of therapy is associated with the achievement of low rheumatoid arthritis (RA) activity.Objectives:to assess the relationship between the early clinical response to tofacitinib and the decrease in RA activity after 3 and 6 months.Methods:Study group included 88 patients with RA, their age was 53±11,5, 79.3% of women, 89.8% of RF “+”, DAS28 5.2±1.2, receiving DMARDs (methotrexate 59.5% and leflunomide 19.8%), who were administered with tofacitinib 5 mg 2 times a day due to inefficacy or intolerance of biological DMARDs. There were assessed the pain severity using Brief pain inventory (BPI) questionnaire, the presence of neuropathic pain component (NPC) using PainDETECT questionnaire and signs of CS using Central Sensitisation Inventory (CSI) questionnaire at early time after tofacitinib administration, RA activity using DAS28 after 3 and 6 months.Results:The mean pain severity at baseline was 5.3±2.0 according to the visual analogue scale (VAS 0-10), 51.1% of patients had signs of central sensitization (CSI ≥ 40), 15.9% had NPC (PainDETECT ≥18). 7 days after tofacitinib intake there was statistically reliable reduction of pain severity – up to 4.1±1.8 (р<0.05) and CS – CSI from 40.4±13.5 to 36.5±12.5 (р=0.01). After 28 days, the effect was higher: the pain level (VAS) was 2.8±1.6 (p=0.000), PainDETECT decreased from 11.8±5.6 to 6.8±3.1 (p=0.000), CSI – to 31.6±13.9 (p=0.000). DAS28 after 3 and 6 months was 3.7±1.3 and 3.6±1.2. The number of patients with pain decrease of ≥50% after 28 days of therapy was 59.9%. Low RA activity after 3 months. (DAS28 ≤3.2) was achieved in 64.4% of patients. There was a clear correlation between the number of patients with significant pain reduction at 28 days and the number of patients with low RA activity after 3 and 6 months (rS=0.548, p=0.000; rS=0.790, p=0.000). Six patients withdrew from the study due to inefficacy or social reasons. There were no serious adverse reactions.Conclusion:The application of JAK inhibitor tofacitinib allows to reach a fast analgesic effect and reduce CS signs. An early clinical response to tofacitinib (pain relief) predicts a decrease in RA activity after 3 and 6 months of the therapy.Limitation: Open-label observatory study.Disclosure of Interests:None declared

THU0326 TOFACITINIB IN THE TREATMENT OF SEVERE AND REFRACTORY BEHÇET’S DISEASE: A SINGLE-CENTRE EXPERIENCE IN CHINA

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 393.1-393
Author(s):  
J. Liu ◽  
L. Sun ◽  
F. Zhang ◽  
W. Zheng
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Efficacy And Safety ◽  
Jak Inhibitors ◽  
Gastrointestinal Involvement ◽  
Behcet's Disease ◽  
Intestinal Ulcers

Background:Small-molecule JAK inhibitors have succeeded in the treatment of rheumatoid arthritis, psoriasis, and inflammatory bowel disease1. Tofacitinib is under investigation for various autoimmune diseases2, but its effectiveness on Behçet’s disease(BD) has not been demonstrated.Objectives:We aimed to investigate the efficacy and safety of Tofacitinib in the treatment of severe and refractory BD.Methods:We retrospectively analyzed the efficacy and safety profile of Tofacitinib in treating severe and refractory BD patients in our hospital from 2017 to 2020.Results:Thirteen BD patients (7 males and 6 females) were enrolled, with a mean age and median course of 40.6±14.7 years and 84 months (60, 132). Vascular/cardiac, gastrointestinal, and articular involvement were presented in 5, 6, and 2 patients, respectively. Three patients had multiple arterial stenosis or occlusion, two presented with aortic root dilation with aortic valve regurgitation, and one experienced perivalvular leakage (PVL). All the six patients with gastrointestinal involvement had multiple episodes of ileocecal and colon ulcers, intestinal bleed, and three had anastomotic ulcers or leaks.All the patients had received high-dose glucocorticoids and immunosuppressants before tofacitinib therapy, they displayed poor response with evidence of disease progression; furthermore, three patients with gastrointestinal involvement and one patient with polyarthritis had failed anti-TNF antibody treatment. They were then treated with Tofacitinib, 5mg twice daily, with background glucocorticoids and immunosuppressants, for a median of 6 months (range 4 to 19).After a median follow-up of 7 (5, 19) months, the ESR and CRP level decreased significantly (21(8, 50) mm/h vs 8(3, 19.5) mm/h, P<0.01, and 25(5.85, 49.5) mg/L vs 1.89(0.44, 6.65) mg/L, P<0.01, respectively). All patients with vascular/cardiac and articular involvement achieved clinical improvement. Vascular lesions of three patients were radiologically stable, no progressive aneurysm or PVL was observed. Two patients with intestinal ulcers revealed complete mucosal healing; the other three had sustained elevation of ESR and CRP, active mucosal ulcers, recurrent bleeding, or fistula formation. The dose of corticosteroids was tapered in six cases (46.2%), furthermore, the number of immunosuppressants lessened in seven cases. However, two patients had herpes zoster infection during follow up, while being treated with five to six immunosuppressants in addition to Tofacitinib for refractory intestinal ulcers.Conclusion:Our study suggests that Tofacitinib is effective for the treatment of vascular and articular BD; given the limited data, its therapeutic effect on gastrointestinal BD could not be validated. We have to be cautious of infectious risk for severely immunocompromised patients. Further large-scale prospective studies are warranted to confirm the therapeutic potential of JAK inhibitors in BD patients.References:[1]Banerjee, S., Biehl, A., Gadina, M., Hasni, S. & Schwartz, D. M. JAK–STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects. Drugs 77, 521–546 (2017).[2]Fragoulis, G. E., Mcinnes, I. B. & Siebert, S. JAK-inhibitors. New players in the field of immune-mediated diseases, beyond rheumatoid arthritis. Rheumatol. (United Kingdom) 58, i43–i54 (2019).Disclosure of Interests:None declared

scholarly journals Effectiveness and Safety of Subcutaneous Abatacept in Biologic-Naïve RA Patients at Week 52: A Japanese Multicenter Investigational Study (ORIGAMI Study)

2021 ◽  
Author(s):  
Naoto Tamura ◽  
Takanori Azuma ◽  
Kenta Misaki ◽  
Rei Yamaguchi ◽  
Fuminori Hirano ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Health Assessment ◽  
Disease Activity Index ◽  
Treatment Retention ◽  
Low Disease Activity ◽  
Moderate Disease ◽  
Moderate Disease Activity

Abstract Objectives To evaluate the effectiveness and safety of abatacept over 52 weeks in biologic-naïve rheumatoid arthritis (RA) patients with moderate disease activity in the prospective, 5-year, observational study (ORIGAMI study) in Japan. Methods Abatacept 125 mg was administered subcutaneously once a week. Clinical outcomes included Simplified Disease Activity Index (SDAI) remission at Week 52 (primary endpoint), Japanese Health Assessment Questionnaire (J-HAQ), EuroQol 5-Dimension (EQ-5D), treatment retention, and safety. Results were compared with those of csDMARD controls from the ongoing Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry. Results Overall, 325 patients were enrolled, with a mean age of 66.9±12.7 years. The proportion of patients achieving SDAI remission (≤3.3) at Week 52 was 18.9% (95% CI: 14.3–23.6) and low disease activity (≤11) was 53.3% (95% CI: 47.4–59.1). A significant improvement was observed in J-HAQ and EQ-5D over 52 weeks in both the abatacept and csDMARD groups. The probability of abatacept treatment retention at Week 52 was 69.9% (95% CI: 64.7–75.5). AEs and serious AEs were reported in 50.0% and 12.1% of patients, respectively. Conclusions Abatacept significantly improved disease activity, physical disability, and quality of life for up to 52 weeks in RA patients in a real-world setting.

scholarly journals Problems of pain and quality of life in rheumatoid arthritis: focus on baricitinib

2020 ◽  
Vol 58 (4) ◽  
pp. 420-427
Author(s):  
A. E. Karateev
Keyword(s):  
Rheumatoid Arthritis ◽  
Intracellular Signaling ◽  
Janus Kinase ◽  
Effective Control ◽  
Signal Transducers ◽  
Intracellular Signaling Pathway ◽  
Autoimmune Inflammation ◽  
Immune Mediated

Modern therapy for rheumatoid arthritis (RA) allows not only to reduce the activity of immune-mediated inflammation and slow down the progression of the disease, but also to quickly eliminate the main symptoms that cause the most concern to patients, such as pain, functional disorders, fatigue. This action has an inhibitor of Janus kinases 1/ 2 – baricitinib, which quickly reduces the activity of inflammation, provides remission in RA, and has a high analgesic effect. The review discusses the role of autoimmune inflammation and the intracellular signaling pathway JAK/STAT (Janus kinase/signal transducers and activators of transcription) in the pathogenesis of chronic pain in RA, the role of baricitinib for effective control of pain intensity and fatigue. 

scholarly journals Clinical significance of Janus kinase inhibitors in the therapy of rheumatoid arthritis: achievements and prospects

2019 ◽  
Vol 13 (4) ◽  
pp. 116-123 ◽  
Author(s):  
V. I. Mazurov ◽  
I. B. Belyaeva
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Weight ◽  
Intracellular Signaling ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Janus Kinase Inhibitors ◽  
Expected Effect ◽  
Signaling Systems ◽  
Disease Modifying

Significant successes in the use of biological agents (BA) have been achieved in the treatment of rheumatoid arthritis (RA); nonetheless, about 36% of patients cannot respond to therapy or achieve the expected effect. A new area in the treatment of RA is the use of Janus kinase (JAK) inhibitors, targeted synthetic disease-modifying anti-rheumatic drugs (chemical molecules with a molecular weight <1 kDa for oral administration) that inhibit the activity of intracellular signaling systems. The authors consider the clinical achievements and prospects, which open the use of JAK inhibitors in the treatment of RA.

Biologics in rheumatoid arthritis

2014 ◽  
Vol 1 (1) ◽  
pp. 34-37
Author(s):  
Khalid Testas ◽  
◽  
Samy Slimani ◽  
Lamia Djeghader ◽  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
B Cells ◽  
Disease Activity ◽  
Small Molecule ◽  
Radiographic Progression ◽  
Tnf Alpha ◽  
Janus Kinases ◽  
Low Disease Activity ◽  
The World

Remission of low disease activity has become the main goal in the management of rheumatoid arthritis (RA), thanks to immunosuppressants but more importantly to a new emerging drug called biologics. Biologics used in RA have proved their efficacy on symptoms as well as radiographic progression, and they have been integrated into the recommendations for the management of RA. TNF alpha inhibitors with their five different molecules are the most prescribed bDMARDs in the world since their approval during the 1990s. Since then, more molecules were made available, targeting other compounds of the rheumatoid inflammation: IL1 (Anakinra), CD20 B cells (Rituximab), costimulation molecules of T cells (Abatacept), IL6 (Tocilizumab) and more recently small molecule inhibitors (Janus kinases), Tofacitinib.

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