Traditional Disease-modifying Antirheumatic Drugs Research Articles

The serological immunogenicity of the third and fourth doses of COVID-19 vaccine in patients with inflammatory rheumatic diseases on different biologic or targeted DMARDs: a Swedish nationwide study (COVID-19-REUMA).

Results from this study provide further evidence that additional doses of COVID-19 vaccines are immunogenic and result in satisfactory antibody response in a majority of patients with inflammatory rheumatic diseases (IRD) receiving potent immunomodulating treatments such as biological or targeted disease-modifying anti-rheumatic drugs (DMARDs) given as monotherapy or combined with traditional DMARDs. We observed that rituximab treatment, both as monotherapy and combined with csDMARDs, impaired antibody response, and only roughly 50% of patients developed a satisfactory antibody response including response to omicron subvariants after the third vaccine. In addition, higher IgG levels at the last rituximab course before the third vaccine dose and a longer time after the last rituximab treatment increased the chance of a satisfactory antibody response. These results indicate that rituximab-treated patients should be prioritized for additional vaccine doses. EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) with number 2021-000880-63.

Updated American College of Rheumatology/American Association of Hip and Knee Surgeons guideline for the perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty 2022

The article presents updated guidelines developed by the American College of Rheumatology and the American Association of Hip and Knee Surgeons on the perioperative treatment of patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, juvenile idiopathic arthritis and systemic lupus erythematosus undergoing elective total hip or total knee arthroplasty. The perioperative use of anti-rheumatic drug therapy, including traditional disease-modi fying antirheumatic drugs, biologic agents, targeted synthetic small-molecule drugs and glucocorticoids. All recommendations are conditional and based on the results of retrospective clinical studies, which should be taken into account in decisionmaking when choosing perioperative antirheumatic therapy.

Etanercept for patients with juvenile idiopathic arthritis: drug levels and influence of concomitant methotrexate: observational study

BackgroundEtanercept (ETN) is widely used tumour necrosis factor (TNF) blocker in the treatment of juvenile idiopathic arthritis (JIA) when traditional synthetic disease modifying antirheumatic drug (sDMARD) therapy is not sufficient. There is limited information about the effects of methotrexate (MTX) on serum ETN concentration in children with JIA. We aimed to investigate whether ETN dose and concomitant MTX would effect ETN serum trough levels in JIA patients, and whether concomitant MTX have an influence on the clinical response in patients with JIA receiving ETN.MethodsIn this study, we collected the medical record data of 180 JIA patients from eight Finnish pediatric rheumatological centres. All these patients were treated with ETN monotherapy or combination therapy with DMARD. To evaluate the ETN concentrations, blood samples of the patients were collected between injections right before the subsequent drug. Free ETN level was measured from serum.ResultsNinety-seven (54%) of the patients used concomitant MTX, and 83 (46%) received either ETN monotherapy or used sDMARDs other than MTX. A significant correlation was noted between ETN dose and drug level [r = 0.45 (95% CI: 0.33–0.56)]. The ETN dose and serum drug level were correlated (p = 0.030) in both subgroups – in MTX group [r = 0.35 (95% CI: 0.14–0.52)] and in non-MTX group [r = 0.54 (95% CI: 0.39–0.67)].ConclusionIn the present study, we found that concomitant MTX had no effect on serum ETN concentration or on clinical response. In addition, a significant correlation was detected between ETN dose and ETN concentration.

Clinical characteristics of 18 children with chronic nonbacterial osteomyelitis

Objective: To investigate the clinical features of children with chronic nonbacterial osteomyelitis (CNO), and raise awareness among clinicians. Methods: In this retrospective study, 18 patients with CNO who were diagnosed in Children's Hospital of Fudan University from January 2015 to December 2021 were included. Results: Eighteen children with CNO (12 males, 6 females) were identified. Their age at onset was 9 (5, 11) years, the delay in diagnosis was 2 (1, 6) months, and follow-up-was 17 (8, 34) months. The most common symptoms were fever in 14 children, as well as bone pain and (or) arthralgia in 14 children. In terms of laboratory results, normal white blood cell counts were observed at onset in 17 patients; increased erythrocyte sedimentation rate (ESR) in all patients; increased C reactive protein (CRP) over the normal value in 14 patients. Of the 18 patients, 2 had positive antinuclear antibodies, while none had positive human leukocyte antigen-B27 or rheumatoid factor. Imaging examination revealed that all the patients had symmetrical and multifocal skeletal lesions. The number of structural lesions detected by imaging investigation was 8 (6, 11). The most frequently affected bones were tibia in 18 patients and femur in 17 patients. Bone biopsy was conducted in 14 patients and acute or chronic osteomyelitis manifested with inflammatory cells infiltration were detected. Magnetic resonance imaging (MRI) found bone lesions in all the patients and bone scintigraphy were positive in 13 patients. All the patients were treated with nonsteroidal anti-inflammatory drugs, among whom 10 cases also treated with oral glucocorticoids, 9 cases with traditional disease modifying anti-rheumatic drugs, 8 cases with bisphosphonates and 6 cases with tumor necrosis factor inhibitors. The pediatric chronic nonbacterial osteomyelitis disease activity score, increased by 70% or more in 13 patients within the initial 6-month follow-up. Conclusions: The clinical manifestations of CNO are lack of specificity. The first symptom of CNO is fever, with or without bone pain and (or) arthralgia, with normal peripheral blood leukocytes, elevated CRP and (or) ESR. Whole body bone scanning combined with MRI can early detect osteomyelitis at subclinical sites, and improve the diagnostic rate of CNO.

Recommendations for diagnosis and treatment of ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disease mainly affecting the sacroiliac joints, spine and peripheral joints. In China, standardized diagnosis and treatment of AS is still to be popularized. Based on the evidence and guidelines from China and other countries, Chinese Rheumatology Association developed standardization of diagnosis and treatment of AS. The purposes are: (1) to standardize the diagnosis and evaluation of AS; (2) to promote rational use of non-steroidal anti-inflammatory drugs, biological as well as traditional disease modifying anti-rheumatic drugs, so as to improve the patient's quality of life.

2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.

To develop updated guidelines for the perioperative management of disease-modifying medications for patients with rheumatic diseases, specifically those with inflammatory arthritis (IA) and those with systemic lupus erythematosus (SLE), undergoing elective total hip arthroplasty (THA) or elective total knee arthroplasty (TKA). We convened a panel of rheumatologists, orthopedic surgeons, and infectious disease specialists, updated the systematic literature review, and included currently available medications for the clinically relevant population, intervention, comparator, and outcomes (PICO) questions. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations using a group consensus process. This guideline updates the 2017 recommendations for perioperative use of disease-modifying antirheumatic therapy, including traditional disease-modifying antirheumatic drugs, biologic agents, targeted synthetic small-molecule drugs, and glucocorticoids used for adults with rheumatic diseases, specifically for the treatment of patients with IA, including rheumatoid arthritis and spondyloarthritis, those with juvenile idiopathic arthritis, or those with SLE who are undergoing elective THA or TKA. It updates recommendations regarding when to continue, when to withhold, and when to restart these medications and the optimal perioperative dosing of glucocorticoids. This updated guideline includes recently introduced immunosuppressive medications to help decision-making by clinicians and patients regarding perioperative disease-modifying medication management for patients with IA and SLE at the time of elective THA or TKA.

2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.

To develop updated guidelines for the perioperative management of disease-modifying medications for patients with rheumatic diseases, specifically those with inflammatory arthritis (IA) and those with systemic lupus erythematosus (SLE), undergoing elective total hip arthroplasty (THA) or elective total knee arthroplasty (TKA). We convened a panel of rheumatologists, orthopedic surgeons, and infectious disease specialists, updated the systematic literature review, and included currently available medications for the clinically relevant population, intervention, comparator, and outcomes (PICO) questions. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations using a group consensus process. This guideline updates the 2017 recommendations for perioperative use of disease-modifying antirheumatic therapy, including traditional disease-modifying antirheumatic drugs, biologic agents, targeted synthetic small-molecule drugs, and glucocorticoids used for adults with rheumatic diseases, specifically for the treatment of patients with IA, including rheumatoid arthritis and spondyloarthritis, those with juvenile idiopathic arthritis, or those with SLE who are undergoing elective THA or TKA. It updates recommendations regarding when to continue, when to withhold, and when to restart these medications and the optimal perioperative dosing of glucocorticoids. This updated guideline includes recently introduced immunosuppressive medications to help decision-making by clinicians and patients regarding perioperative disease-modifying medication management for patients with IA and SLE at the time of elective THA or TKA.

2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty

To develop updated American College of Rheumatology/American Association of Hip and Knee Surgeons guidelines for the perioperative management of disease-modifying medications for patients with rheumatic diseases, specifically those with inflammatory arthritis (IA) and those with systemic lupus erythematosus (SLE), undergoing elective total hip arthroplasty (THA) or elective total knee arthroplasty (TKA). We convened a panel of rheumatologists, orthopedic surgeons, and infectious disease specialists, updated the systematic literature review, and included currently available medications for the clinically relevant population, intervention, comparator, and outcomes (PICO) questions. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations using a group consensus process. This guideline updates the 2017 recommendations for perioperative use of disease-modifying antirheumatic therapy, including traditional disease-modifying antirheumatic drugs, biologic agents, targeted synthetic small-molecule drugs, and glucocorticoids used for adults with rheumatic diseases, specifically for the treatment of patients with IA, including rheumatoid arthritis and spondyloarthritis, those with juvenile idiopathic arthritis, or those with SLE who are undergoing elective THA or TKA. It updates recommendations regarding when to continue, when to withhold, and when to restart these medications and the optimal perioperative dosing of glucocorticoids. This updated guideline includes recently introduced immunosuppressive medications to help decision-making by clinicians and patients regarding perioperative disease-modifying medication management for patients with IA and SLE at the time of elective THA or TKA.

Rheumatoid arthritis: current therapeutics compendium.

Rheumatoid arthritis is a common chronic inflammatory disease with substantial economic, social, and personal costs. Its pathogenesis is multifactorial and complex. The ultimate goal of rheumatoid arthritis treatment is stopping or slowing down the disease progression. In the past two decades, invention of new medicines, especially biologic agents, revolutionized the management of this disease. These agents have been associated with an improved prognosis and clinical remission, especially in patients who did not respond to traditional disease-modifying anti-rheumatic drugs (DMARDs). Improvement in the understanding of the rheumatoid arthritis pathogenesis leads to the development of novel biologic therapeutic approaches. In the present paper, we summarized the current therapeutics, especially biologic agents, available for the treatment of rheumatoid arthritis.

Эффективность и безопасность отмены ингибиторов фактора некроза опухоли альфа при длительной ремиссии ювенильного идиопатического артрита без системных проявлений: когортное исследование

The biological agents when long-term clinical remission of juvenile idiopathic arthritis (JIA) is achieved is necessary to reduce the risk of side effects and costs and to minimize the non-economic burden of therapy on patients and their families. Objective. To evaluate the efficacy and safety of discontinuing inhibitors of tumor necrosis factor alpha (TNF-α) in patients with JIA without systemic manifestations due to long-term clinical remission. Patients and methods. A total of 137 patients with JIA (27.0% male, mean age: 10 years) were enrolled in this study, of whom 95 (69.3%) received etanercept (0.8 mg/kg/week) and the rest – adalimumab (24 mg/m2 once every two weeks). The retrospective study included patients with JIA without systemic manifestations and disease remission of ≥24 months, during which the patients received TNF-α inhibitors. The latter were discontinued as directed by a physician or due to unavailability of the drug. The primary outcome measure of the study was maintenance of clinically inactive disease status (according to American College of Rheumatology criteria) for 6 months (<210 days including 30 days’ tolerance for deviation from the recommended rehospitalization time) after discontinuation of therapy with TNF-α inhibitors. Results. At the time of TNF-α withdrawal, the median duration of JIA was about 6 years, the duration of TNF-α therapy was 3.5 years, and remission lasted for 3 years. After TNF-α withdrawal, 60 (43.8%) patients continued therapy with traditional disease-modifying antirheumatic drugs (DMARs). In the first 210 days after TNF-α discontinuation, 92 (67.2%) patients with JIA maintained the inactive disease status. The median time for the development of JIA exacerbations in 45 patients was 123 (95; 150) days. Biological agents therapy was resumed in 42 of 45 patients, and the inactive disease status was achieved in 41 cases. DMARs were received by 23 (55%) of 42 patients on therapy with biological agents. Conclusion. In two thirds of patients with JIA, the discontinuation of TNF-α inhibitors due to long-term clinical remission did not lead to disease exacerbations in the next six months. The resumption of biological agents therapy in case of JIA worsening allows most patients to reach the status of clinically inactive disease. Key words: genetically engineered biopharmaceutical drugs, tumor necrosis factor inhibitors, juvenile idiopathic arthritis, therapy withdrawal, long-term remission, clinically inactive disease

Remission is not maintained over 2 years with hematopoietic stem cell transplantation for rheumatoid arthritis: A systematic review with meta-analysis.

BACKGROUNDHematopoietic stem cell (HSC) transplantation (HSCT) is being accepted as a standard of care in various inflammatory diseases. The treatment of rheumatoid arthritis (RA) has been closely evolving with the understanding of disease pathogenesis. With the rising resistance to the traditional disease-modifying anti-rheumatic drugs and targeted biological therapy, researchers are in pursuit of other methods for disease management. Since the ultimate goal of the ideal treatment of RA is to restore immune tolerance, HSCT attracts much attention considering its reparative, paracrine, and anti-inflammatory effects. However, a systematic review of studies on HSCT in RA is lacking.AIMTo investigate the role of HSCT in the management of RA.METHODSA detailed search of PubMed, Scopus, EMBASE, Cochrane, and the Web of Science databases was made to identify the relevant articles till September 2020 following Cochrane and PRISMA guidelines. We extracted data including the number of patients, source of hematopoietic stem cells, their mobilization and conditioning regimens, results, and complications from the eligible studies. Results were dichotomized into success (ACR 50/70) and failure (ACR 20) based on the improvement from baseline characteristics. The methodological quality of the included studies was also assessed. Analysis was performed using OpenMeta[Analysis] software. RESULTSWe included 17 studies (1 randomized controlled trial, 11 prospective, and 5 retrospective studies) with 233 patients for analysis. HSCT provided a significantly beneficial overall improvement in the clinical grades of ACR criteria (Z = 11.309, P < 0.001). However, the remission was noted only till 24 mo and later on the significance of the result was lost (Z = 1.737, P = 0.082). A less than 1% treatment-related mortality was noted from the included studies. No major drug-related toxicities were noted in any of the included studies. All patients who underwent allogeneic HSCT received immunosuppression in the conditioning regimen to counteract the graft-vs-host reaction which made them vulnerable to infections. It is noted that the source of hematopoietic stem cells did not play a role in altering the functional outcome and both autologous (Z = 9.972, P < 0.001) and allogenic (Z = 6.978, P < 0.001) sources produced significant improvement in the outcome compared to the pre-operative state despite having a significant heterogeneity among the studies reporting them (I2 = 99.4, P < 0.001). CONCLUSIONAlthough the available literature is encouraging towards the use of HSCT in refractory cases with significant improvement from baseline till 2 years, the inclusion of HSCT into the standard of care of RA needs further exploration.

Tofacitinib effectiveness in Blau syndrome: a case series of Chinese paediatric patients

ObjectiveBlau syndrome (BS), a rare, autosomal-dominant autoinflammatory syndrome, is characterized by a clinical triad of granulomatous recurrent uveitis, dermatitis, and symmetric arthritis and associated with mutations of the nucleotide-binding oligomerization domain containing 2 (NOD2) gene. Aim of this study was to assess the efficacy of tofacitinib in Chinese paediatric patients with BS.MethodsTofacitinib was regularly administered to three BS patients (Patient 1, Patient 2, and Patient 3) at different dosages: 1.7 mg/day (0.11 mg/kg), 2.5 mg/day (0.12 mg/kg), and 2.5 mg/day (0.33 mg/kg). The clinical manifestations of the patients, magnetic resonance imaging results, serological diagnoses, therapeutic measures and outcomes of treatments are described in this report.ResultsThe clinical characteristics and serological diagnoses of all BS patients were greatly improved after the administration of tofacitinib treatment. All patients reached clinical remission of polyarthritis and improvements in the erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and inflammatory cytokines.ConclusionTofacitinib, a Janus kinase (JAK) inhibitor, is a promising agent for BS patients who have unsatisfactory responses to corticosteroids, traditional disease-modifying antirheumatic drugs, and biological agents.

Disease-Modifying Anti-rheumatic Drug Prescription Baihu-Guizhi Decoction Attenuates Rheumatoid Arthritis via Suppressing Toll-Like Receptor 4-mediated NLRP3 Inflammasome Activation.

As a traditional Chinese medicine-originated disease-modifying anti-rheumatic drug prescription, Baihu-Guizhi decoction (BHGZD) is extensively used for the treatment of rheumatoid arthritis (RA) with a satisfying therapeutic efficacy. Mechanically, our previous data indicated that BHGZD may ameliorate RA partially by restoring the balance of the “inflammation-immune” system through regulating the TLR4-c-Fos-IL2-TNF-alpha axis. Toll-like receptor 4 (TLR4) has been revealed to be involved in the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome complex. Thus, the aim of the current study was to determine the regulatory effects of BHGZD on the TLR4–mediated inflammasome activation during RA progression based on the modified adjuvant-induced arthritis model (AIA-M) and the lipopolysaccharide/adenosine triphosphate (LPS/ATP)–induced pyroptosis cellular models. As a result, oral administration of BHGZD exhibited prominent improvement in the disease severity of AIA-M rats, such as reducing the redness and swelling of joints, arthritis incidence, arthritic scores, and diameter of the limb and increasing pain thresholds. In line with the in vivo findings, BHGZD treatment effectively inhibited the LPS/ATP–induced pyroptosis of both Raw264.7 macrophage and MH7A cells in vitro by reducing pyroptotic cell death morphology (swollen cells) and decreasing propidium iodide–positive and terminal deoxynucleotidyl transferase–mediated dUTP-fluorescein nick end labeling (TUNEL)–positive cells. Notably, the increased expression levels of TLR4, NLRP3, interleukin 1β, and interleukin 18 proteins and the elevated activities of caspase-1 and lactic dehydrogenase in in vivo and in vitro disease models were markedly reversed by the treatment with BHGZD. In conclusion, the above findings proved the immunomodulatory and anti-inflammatory activities of BHGZD, especially in pyroptosis, which may be attributed to the activation of TLR4–mediated NLRP3 inflammasome signaling.

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

Presence of anti-citrullinated protein antibodies and costs and disease activity in early rheumatoid arthritis - a 3-year follow-up

Objective: To analyse healthcare utilization, loss of productivity, and disease activity in relation to presence of anti-citrullinated protein antibodies (ACPAs). Method: In total, 447 ACPA-positive and 224 ACPA-negative patients from two early rheumatoid arthritis cohorts, recruited 1996–1998 (cohort 1) and 2006–2009 (cohort 2), were followed during 3 years. Data on disease activity were collected, and patients reported healthcare utilization and days lost from work. Disease activity, healthcare costs, and loss of productivity were compared between ACPA groups. Linear regression was performed, controlling for confounders. Results: Healthcare costs did not differ significantly by ACPA status (EUR 3214 for vs EUR 2174 for ACPA-positive vs ACPA-negative patients in cohort 1, ns; EUR 4150 vs EUR 3820 in cohort 2, ns). Corresponding values for loss of productivity were EUR 9148 vs EUR 7916 (ns) and EUR 5857 vs EUR 5995 (ns). Total prescription of traditional disease-modifying anti-rheumatic drugs was higher in cohort 2 than in cohort 1. Methotrexate prescription was higher in ACPA-positive patients, but biologics did not differ significantly between ACPA groups. Disease activity was significantly more improved in cohort 2, but there was no difference in achieving remission in relation to ACPA status. In cohort 1, 25% of ACPA-positive patients were in remission vs 31% of ACPA-negative (ns) and in cohort 2, 55% vs 60% (ns). Conclusions: With increasing drug treatment for both ACPA-positive and ACPA-negative patients, outcome in ACPA-positive was no more severe than in ACPA-negative patients. Healthcare costs and loss of productivity were similar in the two groups.

Pop a pill or give myself a shot? Patient perspectives of disease-modifying anti-rheumatic drug choice for rheumatoid arthritis.

To assess how patients with rheumatoid arthritis (RA) decide whether to add oral disease-modifying anti-rheumatic drugs (DMARDs) versus injectable biologic DMARDs when methotrexate response is inadequate. Using nominal group technique (NGT), RA patients answered the question "What sort of things are important to you when you make a decision between adding pills versus injectable medications to treat rheumatoid arthritis when methotrexate fails to control RA disease activity?" Patients nominated, discussed, and voted for the responses. Forty-seven RA patients participated: Birmingham (n=6 NG; 21 patients) and New York City (n=4 NG; 26 patients). They were predominantly female (85%), 70% white, with a mean age of 64.5 years and 58% had>10-year RA duration. Present/past DMARDs included methotrexate only in 6%, other traditional DMARDs in 15%, glucocorticoids in combination with traditional DMARDs in 11%, and biologics and/or Jak-kinase inhibitors in 68% of participants. Voted domains in order were: (1) efficacy/effectiveness and the onset/mode of action (78/282 votes); (2) side effects/fear of side effects (84/282 votes); (3) cost including out of pocket, co-payments and patient responsibility (54/282 votes); (4) convenience/frequency of use (27/282 votes); (5) doctor's opinion (20/282 votes); (6) other drugs/comorbidity/other patient's experience/effects on other people (3/282 votes); (7) fear of needles (8/282 votes); and (8) newness of the medication (8/282 votes). We identified the patient perspective regarding the choice between adding oral versus injectable DMARD once methotrexate failed to control RA disease activity. This knowledge can help in shared decision-making for DMARD choice in RA treatment.

SARS-CoV-2 infection among patients with systemic autoimmune diseases.

ObjectivesThis study aimed to evaluate the prevalence of clinically overt SARS-CoV-2 infection (COVID-19) among patients with systemic autoimmune diseases residing in Tuscany, and to compare it with that observed in the general Tuscan population.MethodsIn this cross-sectional study, Tuscan outpatients with systemic autoimmune diseases followed at a tertiary referral centre were telephonically interviewed between April 1st-14th 2020 to collect demographic and clinical data, information on ongoing immunomodulating/immunosuppressive treatments, and on the presence of symptoms suspected of SARS-CoV-2 or of a confirmed infection.Results458 patients were interviewed [74% female, median age 56 years (IQR 43–68)]; 56% of them were receiving corticosteroids, 44% traditional disease-modifying anti-rheumatic drugs (DMARDs), of whom 23% hydroxychloroquine, 5% colchicine, while 41% were on biologic DMARDs (of whom 9% on tocilizumab). Thirteen patients reported symptoms suggesting SARS-CoV-2 infection. Of them, 7 had undergone nasopharyngeal swab and only one was positive and developed severe SARS-CoV-2 complications. Within our cohort, the prevalence of SARS-CoV-2 infection was therefore 0.22% (0.01–1.21%), comparable to that observed in the general population of Tuscany [0.20% (0.20–0.21%), p = .597].ConclusionsPatients with systemic autoimmune diseases do not seem to carry an increased risk of SARS- CoV-2 infection as compared to the general population.

&lt;p&gt;Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cell Therapy for Rheumatoid Arthritis Patients: A Prospective Phase I/II Study&lt;/p&gt;

BackgroundThe traditional anti-inflammation disease-modifying anti-rheumatic drugs (DMARDs) have limited therapeutic effects in rheumatoid arthritis (RA) patients. We previously reported the safety and efficacy of umbilical cord mesenchymal stem cell (UC-MSC) treatment in RA patients that were observed for up to 8 months after UC-MSC infusion. The aim of this study is to assess the long-term efficacy and safety of UC-MSC along with DMARDs for the treatment of RA.Methods64 RA patients aged 18–64 years were recruited in the study. During the treatment, patients were treated with 40 mL UC-MSC suspension product (2 × 107 cells/20 mL) via intravenous injection immediately after the infusion of 100 mL saline. The serological markers tests were used to assess safety and the 28-joint disease activity score (DAS28) and the Health Assessment Questionnaire (HAQ) to assess efficacy.Results1 year and 3 years after UC-MSC cells treatment, the blood routine, liver and kidney function and immunoglobulin examination showed no abnormalities, which were all in the normal range. The ESR, CRP, RF of 1 year and 3 years after treatment and anti-CCP of 3 years after treatment were detected to be lower than that of pretreatment, which showed significant change (P < 0.05). Health index (HAQ) and joint function index (DAS28) decreased 1 year and 3 years after treatment than before treatment (P < 0.05).ConclusionUC-MSC cells plus DMARDs therapy can be a safe, effective and feasible therapeutic option for RA patients.

Effective treatment of TNF\u03b1 inhibitors in Chinese patients with Blau syndrome

ObjectivesBlau syndrome (BS) is a rare dominantly inherited autoinflammatory disorder associated with mutations in the nucleotide-binding oligomerization domain containing 2 (NOD2) gene. Biologic therapy of BS yielded diverse results. We aimed to evaluate clinical features and outcomes of Chinese patients with BS who were treated with tumor necrosis factor (TNF)α inhibitors.MethodsA total of four patients with BS were diagnosed and treated with infliximab (IFX) at the Peking Union Medical College Hospital during 2015 to 2018 and were followed up for 18 months. All patients were systematically studied for treatment outcomes including the clinical manifestations and inflammatory markers. We also conducted a comprehensive literature review about TNFα inhibitor therapy in BS.ResultsFour BS patients were all Chinese Han, and three were women. The mean age of disease onset was 4 ± 3.5 years, and the mean time of diagnosis delay was 19 ± 11 years. All patients received IFX plus methotrexate, and all achieved clinical remission of skin lesions and polyarthritis rapidly, as well as normalization of erythrocyte sedimentation rate and C-reactive protein and improvements in inflammatory cytokines, patient visual analogue scale, physician global assessment, and Short Form (SF)-36, at the first follow-up of 6 months. The disease relapsed in two patients after they lengthened the interval of IFX and discontinued methotrexate. According to the 38 English-language publications, 62 patients with BS were reported who underwent TNFα inhibitor therapy, including IFX used in 31, adalimumab in 24, and etanercept in 7. IFX was well tolerated in 27 patients, while 2 still had uveitis, and the other 2 experienced an adverse drug reaction.ConclusionsEarly recognition and effective treatment of BS are very important to avoid irreversible organ damage. TNFα inhibitors such as IFX may be a promising approach for BS patients who have unsatisfactory response to corticosteroids and traditional disease-modifying antirheumatic drugs.

Arthritis risk with immune checkpoint inhibitor therapy for cancer.

This review summarizes the current evidence on inflammatory arthritis following cancer treatment with immune checkpoint inhibitors (ICI), and the effects of these therapies in patients with preexisting autoimmune arthritis. As the use of ICI for cancer therapy continues to expand, a myriad of immune-related adverse events (irAE) caused by these therapies are being recognized. Arthritis has been increasingly reported as a de novo irAE, presenting sometimes as a well defined disorder, such as rheumatoid arthritis or psoriatic arthritis, and in other occasions as undifferentiated monoarthritis, oligoarthritis, or polyarthritis. Remitting seronegative symmetric synovitis with pitting edema (RS3PE) and tenosynovitis have also been reported. Most published cases are reported as mild to moderate in severity. The most common treatment for arthritis has been systemic corticosteroids, although several patients have been treated with traditional disease-modifying antirheumatic drugs (DMARD), and a few, with biologic DMARD. Arthritis following ICI therapy is pleomorphic. Prompt identification and treatment are imperative to achieve optimal outcomes. Management should be multidisciplinary, including rheumatologists and oncologists, to ensure prompt symptomatic and functional management and continuation of cancer therapy as appropriate.