Class Of Disease-modifying Antirheumatic Drugs Research Articles

Disease-Modifying Medications in Patients with Rheumatoid Arthritis in the USA: Trends from 2016 to 2021.

Disease-modifying anti-rheumatic drugs (DMARDs), since their introduction in 1990, have revolutionized the management of rheumatoid arthritis. Newer DMARDs have recently been approved, influencing treatment patterns and clinical guidelines. To update the current prescribing patterns of DMARDs in the pharmacotherapy of rheumatoid arthritis (RA) to include the pandemic era. This was a retrospective cross-sectional multi-year study. Using Optum's Clinformatics® Data Mart Database, we summarized trends in the prevalence of DMARD use in the USA from 2016 to 2021 by year for adult patients ≥ 18 years old with at least one medical RA claim and one pharmacy/medical claim of a DMARD medication. Trends included type of DMARD, class of DMARD (conventional (csDMARDs), biologics [tumor necrosis factor (TNFi) and Non-TNFi), and Janus kinase inhibitors (JAKs)], and triple therapy [methotrexate (MTX), hydroxychloroquine (HCQ), sulfasalazine (SUL)] used. The total sample from 2016 to 2021 was 670,679 commercially insured patients. The average age was 63.7 years (SD 13.6), and 76.7% were female and 70% were White. csDMARDs remain the most prescribed (ranging from 77.2 to 79.2%). Although JAKs were the least prescribed DMARD class, their proportion more than doubled from 2016 (1.5%) to 2021 (4%). MTX utilization declined from 40% in 2016 to 34% in 2021. In contrast, HCQ use increased during the pandemic era from <25% in 2018 to 30% in 2021. Although there is evidence of the therapeutic benefit of triple therapy, its use was very low (~1%) compared to biologics only (~17%) or biologics+MTX (~10%). About half of patients with RA were on DMARDs. As expected, csDMARDs were highly used consistently. The COVID-19 pandemic might have influenced the use of HCQ and infusion DMARDs. Triple therapy use remains low.

OA20 Combining B cell depletion and JAKi for difficult-to-treat rheumatoid arthritis

Abstract Introduction Difficult-to-treat rheumatoid arthritis (D2T RA) remains an area of unmet need in rheumatology. Despite the increasing availability of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) choices to treat RA, a significant proportion of patients with D2T RA still fail to achieve low disease activity or remission [1]. Here we present the case of a patient with D2T RA refractory to multiple lines of conventional DMARDs (cDMARDs) and biological DMARDs (bDMARDs), who has been managed with a novel combination of rituximab and filgotinib, with no adverse side effects or increased infection risk frequency in his follow up period to date. Case description A 51-year-old man was referred with a history of strongly seropositive RA which had failed multiple conventional treatments. He was diagnosed with seropositive RA in his teens and by the age of 23, had extensive deforming arthritis with fixed flexion in his knees for which he has had required arthroplasties. Previous cDMARDs include methotrexate, leflunomide, sulphasalazine and hydroxychloroquine, all of which were stopped due to side effects or inefficacy. He had primary failure to etanercept, adalimumab, tocilizumab, abatacept, and rituximab. He previously had good efficacy on the combination of infliximab and methotrexate but developed secondary failure after a decade. Golimumab and methotrexate worked well in combination but was stopped when methotrexate was discontinued due to a persistent macroscopic haematuria. Other comorbidities include type 1 diabetes, hypercholesterolaemia, hypothyroidism, and osteoporosis. On initial review he was on a combination of baracitinib and sulphasalazine. However, he had evidence of persistent high disease activity with a disease activity score (DAS-28) of 6.09 with 9 tender joints, 4 swollen joints, and VAS 7/10. Inflammatory markers were elevated with an ESR of 60 mm/hr and CRP of 16mg/L. He switched to upadacitinib, but this was discontinued due to headaches and lack of clinical benefit. He was re-trialled on infliximab with concurrent tacrolimus, but this was not effective and he had anti-infliximab antibodies of &amp;gt; 200ng/mL (0-10 ng/mL) on immunological testing. Combination rituximab (1 gram days 1 and 15) and cyclophosphamide (750mg days 3 and 17) was initiated next, which helped with his jaw synovitis, but not the remainder of his joints, and developed gastrointestinal side effects with the cyclophosphamide. Following MDT discussion, filgotinib was introduced and he has managed to reduce his prednisolone dose by 3mg to his current 5mg dose, with no significant deterioration in his joints and an improvement in his inflammatory markers. Discussion Our patient fulfils the EULAR definition of D2T RA with failure to multiple biologic and conventional DMARDs, persisting clinical and biochemical evidence of active disease and difficulties with tapering glucocorticoid treatment [2]. This has had a significant impact on his quality of life and activities of daily living. Insulin dependent diabetes adds to the complexities of his management, as though his diabetes is well controlled at baseline with the use of a closed loop insulin system, the recurrent need for steroids had a knock-on sequela on his blood glucose control, and further contributed to his osteoporosis and cardiovascular risk. B cells have been identified as key contributors in the development of RA [3]. The synovial membrane of RA patients is known to contain B cell derived plasma cells which produce RF, with RF positivity being associated with aggressive articular disease and increased extra-articular manifestations [4]. Following the promising outcomes demonstrated in a randomized, double blind, controlled study by Edwards et al [5], we attempted B cell depletion with rituximab in combination with cyclophosphamide. Unfortunately, the cyclophosphamide could not be continued as he developed gastrointestinal side effects and the combination only conferred marginal benefit. Blood tests done 6 months following rituximab did show a depletion in his B cell count from 294 to 0, and in his RF from 864 to 276. Given the infection risks with prolonged depletion of his peripheral blood B cell counts, filgotinib was introduced given its rapid onset of action and short half-life, with the benefits of JAKi over other classes of DMARDs in D2T RA patients being demonstrated by Ochi et al [6]. Reassuringly, there has been no adverse side effects or major infections in his follow up period to date. Key learning points This case highlights the complexities of managing a patient with D2T RA. Biologics are now the standard of care in RA, but despite the wide range available, 15% of patients are refractory to treatment, and sustained remission is only achieved in less than 50% [7]. The use of concomitant dual biologic therapy to neutralize multiple inflammatory pathways appears to be a promising strategy, but there is a paucity of evidence on the effectiveness and safety of combining two bDMARDs. Previous studies have looked at combining rituximab with a TNFi [8], and a TNFi with abatacept or anakinra, but this was associated with more side effects and no clear advantage [9]. Another study has also shown benefit in adding an IL17 inhibitor to RA patients who have not responded to certolizumab [10]. Ours is the first case that we know of, where rituximab has been used in combination with a JAK inhibitor. We are hoping to approach his treatment strategy by depleting his B cells and combine this with targeting the JAK-STAT pathway to reduce any pro-inflammatory cytokine signaling. The short half-life of filgotinib would be an advantage should there be any adverse side effects or severe infections. Our patient has been strongly engaged in the journey of his RA treatment, but unfortunately, the extent of his previous drug treatments and comorbidities means he is usually excluded from entering any drug trials, and this would similarly be applied to most patients who fall into the D2T RA category. A patient centred treatment approach is especially crucial when undertaking riskier treatment strategies, with all treatment consultations requiring a careful discussion of the risks and benefits. This case emphasizes the need for further research on combination biologic therapies in D2T RA and would add to the growing body of evidence in this area.

AB1596 REAL-LIFE STUDY OF IMMUNOGENECITY AND SAFETY OF THE RECOMBINANT VACCINE AGAINST VARICELLA ZOSTER VIRUS IN PATIENTS WITH RHEUMATIC DISEASES TREATED WITH JANUS KINASE INHIBITORS

BackgroundAdjuvanted recombinant varicella zoster virus subunit vaccine (ARZVV) has been recently approved for preventing reactivation of latent varicella zoster virus in selected groups of patients. Patients with chronic inflammatory diseases are at major risk of this reactivation, developing herpes zoster (HZ) infection (shingles). This risk is further increased under immunosuppressive treatment with janus kinase inhibitors (JAKi). ARZVV is available in Spain since March 2021 for patients treated with JAKi, among other indications. At the present, no real-life post commercialization studies have been published in patients with rheumatic diseases and JAKi vaccinated with ARZVV.ObjectivesTo assess humoral immunogenicity and safety of ARZVV in patients with rheumatic diseases treated with JAKi.MethodsImmunogenicity and short-term safety were evaluated in a cohort of patients treated with Janus Kinase inhibitors in a descriptive prospective study. Participants received two intramuscular doses of the vaccine two months apart. Blood was sampled prior to first and 2-6 weeks after the second vaccine dose. Humoral immune response was tested through a chemiluminescence immunoassay (CLIA), using varicella zoster virus glycoprotein E (gE) as the antigen to measure anti-gE levels. The cut-off for the vaccine response assessment was considered an antibody concentration four times higher in the second measure, compared with the first one, according to the results of the clinical trialNCT01165177. The influence of the different treatments on the humoral response to the vaccine was evaluated. JAKi were separated in three groups, according to their mechanism of action: inhibition of JAK 1 (Upadacitinib and Filgotinib), inhibition of JAK 1 and JAK 2 (Baricitinib) and panJAK inhibition (Tofacitinib). Concomitant treatment influence on the humoral response to the vaccine was also determined: classic disease modifying anti-rheumatic drugs (DMARDs) and corticosteroids. The data about adverse events to the vaccination, disease flare or reactivation on HZ infection were collected.ResultsWe enrolled 30 patients, 23 were woman (76,7%), with a mean age of 55±12 years. Fifteen (50%) were under treatment with upadacitinib, eleven (36,7%) with baricitnib, two (6,7%) with filgotinib and two (6,7%) with tofacitinib. Six (20%) had concomitant treatment with methotrexate and 5 (16,7%) with leflunomide. Ten (33%) had low dose prednisone. Four (13%) reported clinically HZ previously.We found that 16 patients (53,3%) reached the response assessment marked initially of quadrupling their initial antibody count. Type of JAKi did not significantly influence the humoral response, neither did the concomitant treatment with disease-modifying antirheumatic drug or low dose glucocorticoid. Fiftheen patients (50%) presented mild adverse effects; 7 (23%) of them consisted in injection-side pain, and 8 (26,7%) were systemic (myalgia, fatigue or fever). One patient (3,3%) had an ischemic cerebrovascular complication 2 weeks after the first dose. None of the patients presented a disease flare in the following 4 weeks postvaccination, neither HZ infection after 7 months of follow-up.ConclusionLightly more than half of the patients (53%) with rheumatic diseases treated with JAKi reached the immune response assessment stablished. In clinical trials with non-rheumatic immunosuppressed patients, the response was ranged between 65-96%. This difference could be explained due to that it is a real-life study and in the type of disease and immunosuppression. Safety and prevention of HZ infection was high. To confirm these results higher number of patients is needed.

Commentary: Behçet's uveitis - Expanding treatment horizons.

Behçet’s disease is a complex multisystem disease. A standalone positive typing for HLA-B51 is not considered diagnostic, and the diagnosis of this uveitic entity is based on a myriad of multisystem clinical signs that make up the diagnostic criteria.[1] The genetic predisposition to this disease afforded by HLA-B51 positivity (along with other non-HLA genes) has been postulated to get along with an altered microbiome in the gut of Behçet patients, with an additional possible contribution from infectious agents such as Streptococcus sanguinis, to trigger and then sustain an immune response, which disrupts a previously intact T-cell homeostatic environment. This recent understanding has expanded treatment horizons beyond standard treatment protocols, to include biologic therapy, especially tumor necrosis factor-alpha (TNF-α) antagonists, to achieve control of repeated disrupted immune response.[1] Progressive sight-threatening Behçet’s disease involving the entire uveal tract blinds up to 25% of patients within a course of 10 years, after which the disease progression tends to stabilize.[1,2] This mandates an excellent control of inflammation within this all-important “window period” to save the eye either from the direct inflammatory manifestations of Behçet’s uveitis or its potentially blinding complications.[1] The consensus in uveitis management in Behçet’s disease (according to the European Alliance of Associations of Rheumatology [EULAR] and the American Academy of Ophthalmologists’ guidelines) recommends limitation of steroid administration for control of acute inflammation and substituting steroids with conventional disease-modifying antirheumatic drugs (DMARDs) or biologic therapy. Furthermore, the American Academy of Ophthalmology goes a step further to recommend bypassing the “classic DMARDs” in favor of anti-TNF-α agents in severe, sight-threatening uveitis.[3] Thus, EULAR updated its guidelines in 2018 to recommend administering steroids in posterior segment ocular Behçet’s disease patients, but only in combination with steroid-sparing therapies such as azathioprine (AZA), cyclosporine A (CsA), interferon alpha, or monoclonal anti-TNF antibodies.[3] In the current study[4] of Behçet’s disease with ocular lesions from India, all patients have received steroids and 80% patients have been treated with immunosuppression along with steroids. Randomized controlled trials have shown that the antimetabolite AZA and T-cell inhibitor CsA are effective in the treatment of posterior uveitis in Behçet’s disease. Hence, the updated 2018 EULAR guidelines recommended the use of these two drugs (as against others) in the initial therapy of posterior uveitis.[3] Further, the combined use of AZA and CsA, whether as first- or second-line therapy, has shown efficacy in controlling ocular Behçet’s disease (with more periodic side effect monitoring).[1] In the current study from India, AZA and CsA have been combined in 24% of the patients.[4] In Behçet’s disease, TNF-α production by macrophages, CD4+ and CD8+ T cells, and natural killer cells is increased. The reduction of circulating TNF-α has been shown to result in dramatic improvement in the inflammatory activity of patients with severe pan or posterior uveitis.[1] These anti-TNF-α drugs used are recombinant monoclonal antibodies directed against TNF-α. Due to their potent and fast effects, these agents are now used alone or in combination therapy in refractory ocular Behçet’s cases, or sometimes even as first-line treatment in severe sight-threatening attacks.[3] Adalimumab (ADA) is a fully human monoclonal antibody directed against TNF-α and has been tested against a placebo in both active and quiescent, noninfectious uveitis (VISUAL I and VISUAL II studies, respectively). Ocular Behçet’s disease represented 7% of the uveitic cases enrolled in them.[1] Further, other uncontrolled studies have shown significant results regarding the efficacy of ADA in Behçet’s uveitis.[5] Early initiation of ADA in two children with Behçet’s uveitis succeeded in control of the disease activity, allowing tapering of topical and systemic steroids.[6] Comparative studies have been conducted between ADA and the other agent infliximab (IFX), notably a multicenter study on 177 patients with refractory Behçet’s disease uveitis, which found that both agents gave significantly better control in terms of disease activity as the first-line treatment, but the ADA group had higher percentage of patients with better best corrected visual acuity and fewer drug-related reactions.[7] One must remember that exclusion of tuberculosis and other infectious diseases as well as occult malignancies is mandatory before starting therapy with these agents. Also, an additional immunosuppressant (like methotrexate) may be advisable to prevent anti-chimeric, or antihuman, antibody production, which decreases the efficacy of these agents leading to secondary failure.[1] In the current study from India, biologic agents have been used in 40% of the patients; of which ADA was used in 28% and IFX in 12% of patients.[4] Finally, studies have recently reported success with Janus kinase (JAK) inhibitors in the treatment of noninfectious autoimmune uveitis refractory to conventional DMARDs and anti-TNF-α agents. Successful results have been reported with the JAK inhibitor tofacitinib in refractory Behçet’s disease uveitis,[8] and moving forward, these agents shall most likely further expand our treatment horizons for Behçet’s disease.

JAK Inhibition in Patients with Rheumatoid Arthritis: Haemodynamic Effects and Impact on Micro- and Macrovascular Function. Study Design and Rationale.

Rheumatoid arthritis (RA) is characterised by increased rates of cardiovascular disease (CVD), which represents the leading cause of death. Patients with RA presents increased prevalence of hypertension, which substantially contributes to the increased CVD burden associated with the disease. A solid pathophysiological background supports the presence of microvascular dysfunction in RA even in the absence of established CVD, while macrovascular dysfunction in the form of large artery stiffening has been further described. Janus kinase (JAK) inhibitors constitute a novel class of disease-modifying anti-rheumatic drugs (DMARDs) for the management of rheumatoid arthritis (RA). However, the vascular effects of JAK inhibitors in RA patients remain largely understudied. More recent evidence suggests higher risk of major adverse cardiovascular events with JAK inhibition compared to treatment with a TNF inhibitor, and calls for more careful consideration of potential negative effects on the cardiovascular system. The present prospective observational cohort study aims to investigate the impact of JAK inhibitors on ambulatory blood pressure and haemodynamic profile, as well as markers of micro- and macrovasculopathy among patients with RA.

Non-biologic, steroid-sparing therapies for non-infectious intermediate, posterior, and panuveitis in adults.

Non-infectious intermediate, posterior, and panuveitis (NIIPPU) represent a heterogenous collection of autoimmune and inflammatory disorders isolated to or concentrated in the posterior structures of the eye. Because NIIPPU is typically a chronic condition, people with NIIPPU frequently require treatment with steroid-sparing immunosuppressive therapy. Methotrexate, mycophenolate, cyclosporine, azathioprine, and tacrolimus are non-biologic, disease-modifying antirheumatic drugs (DMARDs) which have been used to treat people with NIIPPU. To compare the effectiveness and safety of selected DMARDs (methotrexate, mycophenolate mofetil, tacrolimus, cyclosporine, and azathioprine) in the treatment of NIIPPU in adults. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase, the Latin American and Caribbean Health Sciences database, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform, most recently on 16 April 2021. We included randomized controlled trials (RCTs) comparing selected DMARDs (methotrexate, mycophenolate, tacrolimus, cyclosporine, and azathioprine) with placebo, standard of care (topical steroids, with or without oral steroids), or with each other. We used standard methodological procedures expected by Cochrane. We included 11 RCTs with a total of 601 participants in this review. DMARDs versus control Two studies compared an experimental DMARD (cyclosporine A or enteric-coated mycophenolate [EC-MPS]) plus oral steroid with steroid monotherapy. We did not pool these results into a meta-analysis because the dose of cyclosporine used was much higher than that used in current clinical practice. The evidence is very uncertain about whether EC-MPS plus low-dose oral steroid results in a higher proportion of participants achieving control of inflammation over steroid monotherapy (risk ratio [RR] 2.81, 95% confidence interval [CI] 1.10 to 7.17; 1 study, 41 participants; very low-certainty evidence). The change in best-corrected visual acuity (BCVA) was reported separately for right and left eyes. The evidence for improvement (lower logarithm of the minimum angle of resolution (logMAR) indicates better vision) between the groups is very uncertain (mean difference [MD] -0.03 and -0.10, 95% CI -0.96 to 0.90 and -0.27 to 0.07 for right and left, respectively; 1 study, 82 eyes; very low-certainty evidence). No data were available for the following outcomes: proportion of participants achieving a 2-line improvement in visual acuity, with confirmed macular edema, or achieving steroid-sparing control. The evidence for the proportion of participants requiring cessation of medication in the DMARD versus control group is very uncertain (RR 2.61, 95% CI 0.11 to 60.51; 1 study, 41 participants; very low-certainty evidence). Methotrexate versus mycophenolate We were able to combine two studies into a meta-analysis comparing methotrexate versus mycophenolate mofetil. Methotrexate probably results in a slight increase in the proportion of participants achieving control of inflammation, including steroid-sparing control, compared to mycophenolate at six months (RR 1.23, 95% CI 1.01 to 1.50; 2 studies, 261 participants; moderate-certainty evidence). Change in BCVA was reported per eye and the treatments likely result in little to no difference in change in vision (MD 0.01 logMAR higher [worse] for methotrexate versus mycophenolate; 2 studies, 490 eyes; moderate-certainty evidence). No data were available for the proportion of participants achieving a 2-line improvement in visual acuity. The evidence is very uncertain regarding the proportion of participants with confirmed macular edema between methotrexate versus mycophenolate (RR 0.49, 95% CI 0.19 to 1.30; 2 studies, 35 eyes; very low-certainty). Methotrexate versus mycophenolate may result in little to no difference in the proportion of participants requiring cessation of medication (RR 0.99, 95% CI 0.43 to 2.27; 2 studies, 296 participants; low-certainty evidence). Steroids with or without azathioprine versus cyclosporine A Four studies compared steroids with or without azathioprine (oral steroids, intravenous [IV] steroids, or azathioprine) to cyclosporine A. We excluded two studies from the meta-analysis because the participants were treated with 8 mg to 15 mg/kg/day of cyclosporine A, a significantly higher dose than is utilized today because of concerns for nephrotoxicity. The remaining two studies were conducted in all Vogt-Koyanagi-Harada disease (VKH) populations and compared cyclosporine A to azathioprine or IV pulse-dose steroids. The evidence is very uncertain for whether the steroids with or without azathioprine or cyclosporine A influenced the proportion of participants achieving control of inflammation (RR 0.84, 95% CI 0.70 to 1.02; 2 studies, 112 participants; very low-certainty evidence), achieving steroid-sparing control (RR 0.64, 95% CI 0.33 to 1.25; 1 study, 21 participants; very low-certainty evidence), or requiring cessation of medication (RR 0.85, 95% 0.21 to 3.45; 2 studies, 91 participants; very low-certainty evidence). The evidence is uncertain for improvement in BCVA (MD 0.04 logMAR lower [better] with the steroids with or without azathioprine versus cyclosporine A; 2 studies, 91 eyes; very low-certainty evidence). There were no data available (with current cyclosporine A dosing) for the proportion of participants achieving a 2-line improvement in visual acuity or with confirmed macular edema. Studies not included in synthesis We were unable to include three studies in any of the comparisons (in addition to the aforementioned studies excluded based on historic doses of cyclosporine A). One was a dose-response study comparing cyclosporine A to cyclosporine G, a formulation which was never licensed and is not clinically available. We excluded another study from meta-analysis because it compared cyclosporine A and tacrolimus, considered to be of the same class (calcineurin inhibitors). We were unable to combine the third study, which examined tacrolimus monotherapy versus tacrolimus plus oral steroid, with any group. There is a paucity of data regarding which DMARD is most effective or safe in NIIPPU. Studies in general were small, heterogenous in terms of their design and outcome measures, and often did not compare different classes of DMARD with each other. Methotrexate is probably slightly more efficacious than mycophenolate in achieving control of inflammation, including steroid-sparing control (moderate-certainty evidence), although there was insufficient evidence to prefer one medication over the other in the VKH subgroup (very low-certainty evidence). Methotrexate may result in little to no difference in safety outcomes compared to mycophenolate.

Immunosuppressant Treatment in Rheumatic Musculoskeletal Diseases Does Not Inhibit Elicitation of Humoral Response to SARS-CoV-2 Infection and Preserves Effector Immune Cell Populations.

COVID-19 has proven to be particularly serious and life-threatening for patients presenting with pre-existing pathologies. Patients affected by rheumatic musculoskeletal disease (RMD) are likely to have impaired immune responses against SARS-CoV-2 infection due to their compromised immune system and the prolonged use of disease-modifying anti-rheumatic drugs (DMARDs), which include conventional synthetic (cs) DMARDs or biologic and targeted synthetic (b/ts) DMARDs. To provide an integrated analysis of the immune response following SARS-CoV-2 infection in RMD patients treated with different classes of DMARDs we carried out an immunological analysis of the antibody responses toward SARS-CoV-2 nucleocapsid and RBD proteins and an extensive immunophenotypic analysis of the major immune cell populations. We showed that RMD individuals under most DMARD treatments mount a sustained antibody response to the virus, with neutralizing activity. In addition, they displayed a sizable percentage of effector T and B lymphocytes. Among b-DMARDs, we found that anti-TNFα treatments are more favorable drugs to elicit humoral and cellular immune responses as compared to CTLA4-Ig and anti-IL6R inhibitors. This study provides a whole picture of the humoral and cellular immune responses in RMD patients by reassuring the use of DMARD treatments during COVID-19. The study points to TNF-α inhibitors as those DMARDs permitting elicitation of functional antibodies to SARS-CoV-2 and adaptive effector populations available to counteract possible re-infections.

The prevalence of self-quarantine for preventing COVID 19 involvement in patients with rheumatoid arthritis who used Disease-Modifying Anti-Rheumatic Drugs

Introduction: Rheumatoid Arthritis (RA) is an autoimmune disorder that is treated with classic Disease-Modifying Anti Rheumatic Drugs (DMARDs), which impair the immune system. It seems that self-quarantine is a good method for CVOID-19 prevention in patients with RA. Objectives: The aim of this study was to assessment the prevalence of self-quarantine for preventing COVID 19 involvement in patients with rheumatoid arthritis who used Disease-Modifying Anti-Rheumatic Drugs Methods and Materials: in this descriptive study that was performed in Loghman-Hakim Hospital (Tehran, Iran), patients with RA who took classic DMARDs and were referred to the hospital were assessed based on age, sex, medications, smoking, history of Covid-19 in a relatives, Covid-19 involvement in the patient, Covid-19 symptoms, and observing self-quarantine. Result: the mean age was 53.84 years old and 27.7% were male of one thousand patients with RA who took classic DMARDs. Covid-19 prevalence among these patients was 10.4%. The prevalence of COVID-19 was 21% among patients who didn’t observe self-quarantine and 9.2% among patients who observed self-quarantine. Self-quarantine lowered the risk of Covid-19 by around 60%. Conclusion: self-quarantine is a good method to reduce the prevalence of COVID-19 among RA patients who used classic DMARDs.

Efficacy of TNF-α inhibitors in the treatment of ankylosing spondylitis

Purpose: The study aimed to evaluate and compare the efficacy of TNF-α inhibitors in the treatment of ankylosing spondylitis in everyday medical practice. Materials and methods: We analysed the data of 106 patients with ankylosing spondylitis treated in 2012–2019 with TNF-α inhibitors (etanercept, adalimumab or golimumab) under the drug program of the National Health Fund. The observation period for each patient was 18 months. The disease activity was assessed at 3-month intervals on the basis of BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and ASDAS (Ankylosing Spondylitis Disease Activity Score). Results: The study covered 80 men and 26 women. The mean age of the patients was 37 years. The group receiving etanercept included 50 patients, adalimumab – 39 patients, and golimumab – 17 patients. Due to coexisting offaxial symptoms such as uveitis (n = 20/106) and peripheral arthritis (n = 39/106), some patients were simultaneously receiving classic disease-modifying antirheumatic drugs, i.e. methotrexate (n = 32/106), sulfasalazine (n = 8/106), cyclosporine (n = 5/106), and glucocorticosteroids (n = 14/106). All subgroups showed a significant clinical improvement in the form of a decrease in inflammatory markers and a decrease in disease activity after 3 months of treatment, increasing up to the 6th month. The biological drug was discontinued due to remission (according to BASDAI) in 20/48 patients taking etanercept and in 19/36 patients receiving adalimumab. The observation period following drug discontinuation for both groups was similar and lasted about 7 months. The remission time (according to BASDAI) without treatment was short; 3.55 ± 2.28 months for etanercept vs. 5.21 ± 2.53 months for adalimumab (p = 0.038). Conclusions: The inclusion of TNF-α inhibitors in patients with an unsatisfactory response to treatment with non-steroidal anti-inflammatory drugs resulted in a major reduction of disease activity. There was no statistically significant difference in treatment efficacy between individual TNF-α inhibitors, i.e. etanercept, adalimumab, and golimumab. The group treated with adalimumab was found with a trend towards longer-lasting remission after drug discontinuation, but it was short-lived and a return to treatment was necessary.

COVID-19 and Disease-Modifying Anti-rheumatic Drugs.

Purpose of ReviewPatients on disease-modifying anti-rheumatic drugs (DMARDs) remain concerned about potential risks of severe COVID-19 outcomes. Meanwhile, several DMARDs have been proposed as COVID-19 therapies.Recent FindingsIn patients with autoimmune diseases, baseline glucocorticoid use is associated with severe COVID-19. While classes of DMARDs (e.g., conventional synthetic, targeted synthetic, and biologic) do not appear to be associated with higher risk, specific medications such as rituximab and sulfasalazine may be associated. Randomized clinical trials (RCTs) show that glucocorticoids reduce mortality in severe COVID-19. RCTs suggest other agents, such as baricitinib, may improve COVID-19 outcomes in certain populations.SummaryBaseline glucocorticoid use raises the risk of severe COVID-19 in patients with autoimmune diseases, but glucocorticoids are an effective treatment for those with severe COVID-19. Further research is needed to inform DMARD management in autoimmune disease patients during the pandemic and the role of DMARDs in COVID-19 treatment.

The prevalence of Covid-19 in patients with Rheumatoid Arthritis receiving classic Disease-Modifying Anti Rheumatic Drugs

The prevalence of Covid-19 in patients with Rheumatoid Arthritis receiving classic Disease-Modifying Anti Rheumatic Drugs

COVID-19 and rheumatoid arthritis.

The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality worldwide. Patients with rheumatoid arthritis (RA) face unique challenges during the pandemic, including concerns regarding infection risk, drug shortages, limited access to care, social isolation, and mental health. This review will examine the multifaceted impacts of the COVID-19 pandemic on patients living with RA. In patients with RA, risk factors for severe COVID-19 outcomes include older age and comorbidities, similar to those in the general population. Glucocorticoids, but not other classes of disease-modifying antirheumatic drugs (DMARDs), appear to be associated with a higher risk of severe COVID-19 outcomes. RA patients have been affected by changes in access to care, telemedicine, drug shortages, anxiety, and social isolation, which may contribute to disease flares. Glucocorticoids, but not other DMARDs, are associated with a higher risk of severe COVID-19 outcomes in RA patients. Further studies are needed to explore the impact of specific DMARDs on COVID-19 outcomes, understand the broader implications of the COVID-19 pandemic on RA disease activity, and optimize the use of telemedicine in RA management.

Janus kinase inhibitors for the treatment of rheumatoid arthritis

Rheumatoid arthritis is a chronic inflammatory destructive disorder that affects the joints, muscles, and tendons accompanying various extra-articular manifestations. Traditional disease-modifying anti-rheumatic drugs (DMARDs) represent the basic treatment for rheumatoid arthritis. Over the last 20 years, biologic DMARDs (tumor necrosis factor inhibitors, interleukin-1 inhibitors, interleukin-6 inhibitors, T cell inhibitors, and B cell inhibitors) have been widely used as a novel class of DMARDs that have efficacy and efficiency. Discovery of the underlying pathogenesis of autoimmune disease enables us to develop new target therapies such as a Janus kinase (JAK) inhibitor. Activated JAK is known to activate signal transducers as well as activators of transcription (STAT) signaling. A JAK inhibitor is a type of medication that functions by inhibiting the JAK-STAT signaling pathway. In addition, it is easy to take a JAK inhibitor orally. In Korea, several JAK inhibitors have been approved. This review describes the types of JAK inhibitors, recommended doses, side effects, and updated European Alliance of Associations for Rheumatology guidelines. Clinicians should more often consider JAK inhibitors in the treatment of refractory rheumatoid arthritis in current rheumatology clinics

Dynamic Thiol/Disulphide Homeostasis as Oxidative Stress Marker in Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy.

Seronegative spondyloarthropathies (SpA) are a group of chronic diseases, characterized by axial inflammation, oligoarthritis, and enthesitis. Oxidative stress may contribute to a wide range of diseases such as rheumatologic diseases including SpA. This prospective case-control study was designed to compare the thiol-disulfide levels as a marker of oxidative stress in SpA patients with healthy controls. A total of 144 patients who were diagnosed as undifferentiated spondyloarthropathy (UspA, n=97), ankylosing spondylitis (AS, n=47), and 80 healthy controls were included. Serum native thiol (NT), total thiol (TT), disulfide (D) levels were measured with the fully automated Erel?s method. NT/TT, D/TT, and D/NT ratios were calculated. Thiol-disulfide levels were compared between SpA groups and healthy controls. NT and NT/TT ratios were found to be significantly lower in the SpA group. (p<0.001). Disulfide, D/NT, and D/TT ratios were found to be significantly higher in the SpA group (p <0.001 for each comparison). In pairwise comparisons between SpA subgroups, NT and TT levels were lower in USpA group compared to AS group (P=0.021). Serum disulfide levels were higher in USpA group compared to AS group (P=0,004). Anti-tumor necrosis factor (Anti-TNF) group had lower TT measurements compared to the classical disease-modifying anti-rheumatic drugs (cDMARD) group in patients with SpA (P=0.039). Thiol-disulfide balance is disturbed in favor of disulfide in SpAs patients compared to healthy volunteers. Native and total thiol measurements correlate with acute phase reactants and might be used to monitor disease activity. Anti-TNF therapy might control the oxidative degenerative process better than the classical DMARD in SpA patients.

Cognitive impairment in elderly patients with rheumatic disease and the effect of disease-modifying anti-rheumatic drugs.

Recent development of biologic disease-modifying anti-rheumatic drugs (DMARDs) has led to better control of disease activity among patients with chronic rheumatological diseases. Many patients with rheumatic disease are living longer, adding to the growing elderly population. Rheumatic diseases, most notably rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), are known to increase the risk of cognitive impairment. Systemic inflammation associated with chronic rheumatological diseases has been postulated to be key driver of cognitive decline. Recent development of classic and biologic DMARDs have led to better control of disease activity among patients with rheumatic conditions. It is proposed that strict control of systemic inflammation will significantly lower the risk of cognitive impairment among patients with rheumatic disease. The impact of classic DMARDs on cognitive function appears to be variable. On the other hand, biologic DMARDs, specifically antitumor necrosis factor (TNF) drugs (i.e., etanercept), have been shown to significantly lower the risk of dementia. Experimental studies on IL-1, IL-6, and B and T cell blockade are promising. However, clinical data is limited. Preclinical studies on targeted therapies, specifically JAK/STAT inhibitors, also show promising results. Additional studies are necessary to better understand the impact of these newer biologic agents on cognitive function in elderly patients with rheumatic disease. Key points • Patients with chronic rheumatic conditions are beginning to live longer, adding to the elderly population. • Patients with chronic rheumatologic disease are at increased risk of cognitive impairment compared to the general population. • Recent development of biologic (i.e., TNF, IL-1, IL-6) and targeted drugs (i.e., Janus kinase inhibitors) have led to better control of disease activity. • Current evidence suggests that TNF inhibitors may have beneficial effects on cognitive function. However, evidence on newer biologic and targeted therapies is limited.

[Tight control-Demand for short term control of rheumatoid arthritis].

The prognosis of rheumatoid arthritis (RA) has been significantly improved in recent decades. This is mainly due to earlier detection, better diagnostics and new treatment options, such as the optimized use of classical disease-modifying antirheumatic drugs (DMARD) and biologicals. Other factors involved were earlier intervention, improved availability of information and analyses and certainly also standardization of care (e.g. guidelines). An additional important component is close monitoring of disease activity in order to be able to adapt the treatment in atimely manner and thus prevent damage. The demand for tight control is the subject of this article.

Protective effect of antirheumatic drugs on dementia in rheumatoid arthritis patients

IntroductionRheumatoid arthritis is a systemic inflammatory disease, and classical disease-modifying antirheumatic drugs (cDMARDs) have proven efficacy. It is unknown what impact cDMARDs might have on dementia as an outcome. MethodsIncident diagnoses of rheumatoid arthritis in persons over 18 years from 1995 to 2011 were identified from the UK Clinical Practice Research Datalink. There were 3876 cDMARD users and were propensity score matched to 1938 nonusers, on a wide range of confounders. Impact on dementia was assessed using survival models. ResultscDMARD users were at reduced risk of dementia (hazard ratio: 0.60; 95% confidence interval: 0.42–0.85). The effect was strongest in methotrexate users (hazard ratio: 0.52; 95% confidence interval; 0.34–0.82). DiscussionThe strong effect of cDMARD use on halving of dementia risk requires replication in a trial and may provide an important therapeutic pharmacological treatment.

Management of Juvenile Idiopathic Arthritis: A Clinical Guide.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood. The outcome in patients with JIA has markedly improved with the advent of biologic drugs. Although early aggressive therapy with biologics seems to be very effective, this approach leads to overtreatment in patients who would respond to classic disease-modifying anti-rheumatic drugs. Therefore, methotrexate remains first-line long-term therapy for most children with polyarticular JIA. Tumor necrosis factor-α inhibitors have shown tremendous benefit in children with refractory non-systemic JIA. Similar effects have been observed with interleukin-1 and interleukin-6 blockade in patients with systemic JIA. Correct choice and timely use of available medications to achieve early and sustained remission with as few side effects as possible remain challenges for the treating physician. In this review, a practical, clinically oriented guide to the management of JIA is provided, focusing on pharmacological treatment with non-steroidal anti-inflammatory drugs, intra-articular and systemic corticosteroids, disease-modifying anti-rheumatic drugs, and biologic agents. In addition, issues regarding treatment failure, early aggressive treatment, and drug tapering are discussed, with alternative treatment options being suggested.

Application of Japanese Oriental Medicine for the Treatment of Rheumatoid Arthritis Complicated with Other Serious Diseases

The therapeutic strategy for rheumatoid arthritis (RA) has markedly changed over the past 10 years. It has been recommended to achieve clinical remission and suppress articular destruction by treatment with an effective anti- rheumatic drug from an early stage. However, an alternative strategy to achieve low disease activity due to physical, social, and job-related problems was also recommended in the 2014 update of the recommendation for treating RA to target. In the last version, it is documented that the method of treatment should be determined based on mutual agreement between the physician and patient. It is also important to consider the treatment target and strategy for elderly RA patients in the future. In this trend, classical DMARDs (disease modifying anti-rheumatic drugs) are usually used for patients in whom anti-rheumatic drugs including methotrexate and biologics are contraindicated. We consider that there may be Kampo medicines acting as useful agents for these RA patients. Here, we present the clinical courses of RA patients complicated with respiratory infection and rectal cancer. Furthermore, we discuss the positioning of Kampo medicines in RA therapeutic strategies.

SP0151 Comorbidity in Rheumatic Diseases

Rheumatic diseases are frequently associated with the presence of one or more additional diseases or disorders, called comorbidities. These medical conditions or diseases may represent an active, past, or transient...