ASYNCHRONOUS TELECONSULTATION BY WHATSAPP CHATBOT IN CONTROLLED AXIAL SPONDYLOARTHRITIS (SPA) PATIENTS UNDER BIOLOGICAL THERAPY: CLINICAL RESULTS OF A SINGLE CENTER

BackgroundThe use of telehealth in the control of rheumatic diseases had been scarce, but COVID pandemic forced to try alternatives to classic face-to-face consultation, and an overflow of telehealth consultations appeared, mainly synchronous (phone, video calls), and finally asynchronous. We try to demonstrate that asynchronous WhatsApp teleconsultation is a good alternative, at least for followup of patients that find it difficult to attend face-to-face visits. We chose axial spondyloarthritis (AxSPA) patients under biological therapy with controlled disease and we proposed teleconsultation with a WhatsApp platform chatbot created for this purpose. The chatbot sends PROMS (BASDAI, VAS for patient global disease assessment, ASDAs, and 3 questions for extraarticular disease), and receive feedback and schedule for the following visits.ObjectivesTo prove that teleconsultation through WhatsApp platform is not inferior to face-to-face consultation in terms of maintaining axial SPA patients disease controlled.MethodsProspective study with retrospective control of patients diagnosed of Axial SPA, fulfilling ASAS criteria and with stable disease under biological therapy for the previous year, recruited from 01 jan to 30 nov 2021. We recruited 62 patients, but two of them gave up (personal reasons, one moved to other region), so we finally include 60 patients. We offer them two teleconsultation visits with their personal mobile device, every four months, and a face-to-face final visit one year after inclusion. In the case of lab test or PROMs deviation or when the patient asks for contact (possible via WhatsApp) he/she is called up by the person in charge (nurse/doctor) that solves the question and arranges an additional presential visit if needed. We consider disease controlled if BASDAI <4, ASDAS < 2,1 or if in rheumatologist´s opinion there is no need to change treatment. We collect patient and disease information (age, gender, employment, characteristics of the disease, previous and actual treatment), activity (BASDAI, PCR, ASDAS), physical function (BASFI), and Quality of life (AsQol).Results60 patients (50 men, 83,3%) were included, mean aged 48,22 years (SD 12,128), 36% were under 45 years at the time of inclusion. They were mostly Ankylosing Spondylitis (AS) (90%;only 6 non radiographic SPA), positive HLA B27 (85%) and with longstanding disease (mean 23 years, SD 12,8), and only 6 patients less than five years. 25% had peripheral impairment (arthritis/dactylitis/enthesitis), and more than 40% presented extraarticular manifestations, mainly psoriasis (26,7%) and uveitis (21%)71,7% were under their first biological (TNF inhibitor, mostly adalimumab), 23,3% were refractory to the first, and 3 patients to at least two biologicals. 51,7% of patients were treated with tapered dose of TNF inhibitors. At inclusion 93,3 % presented remission/LDA by ASDAS/BASDAI-RCP. Only 4 patients included presented higher activity scores but were considered clinically controlled.Table 1.We did not find meaningful clinical differences between basal to final visits in BASDAI, BASFI, ASDAS-RCP or AsQOL.3 patients with reduced dose of biological drug needed to increase to standard dose with no other need to treatment adjustment.ConclusionWe consider asynchronous teleconsultation is promising, and not inferior to face to face consultation in terms of keeping disease control and quality of life, especially for follow-up in patients with stable rheumatic disease, The clinical results presented here are consistent with this considerations.AcknowledgementsGrupo INNOBIDE.Disclosure of InterestsNone Declared.

Type 1 diabetes and environment . . . and other stories

A linked ecological analysis of environmental and demographic variables identified several factors, including poor air quality, outdoor light at night, and higher population density that were negatively associated with the incidence of diabetes (Diabetologia doi:10.1007/s00125-020-05087-7). A case-control study using a database of people known to have autoimmune disease raises anxiety about central nervous system inflammatory events (JAMA Neurol doi:10.1001/jamaneurol.2020.1162). A history of exposure to TNF inhibitors carried a threefold increase in risk both of demyelinating diseases, such as multiple sclerosis and optic neuritis, and of non-demyelinating conditions, such as encephalitis, neurosarcoidosis, and vasculitis.

Pre-existing autoimmunity is associated with increased severity of COVID-19: A retrospective cohort study using data from the National COVID Cohort Collaborative (N3C).

BACKGROUND: Identifying individuals with a higher risk of developing severe COVID-19 outcomes will inform targeted or more intensive clinical monitoring and management. To date, there is mixed evidence regarding the impact of pre-existing autoimmune disease (AID) diagnosis and/or immunosuppressant (IS) exposure on developing severe COVID-19 outcomes. METHODS: A retrospective cohort of adults diagnosed with COVID-19 was created in the National COVID Cohort Collaborative enclave. Two outcomes, life-threatening disease, and hospitalization were evaluated by using logistic regression models with and without adjustment for demographics and comorbidities. RESULTS: Of the 2,453,799 adults diagnosed with COVID-19, 191,520 (7.81%) had a pre-existing AID diagnosis and 278,095 (11.33%) had a pre-existing IS exposure. Logistic regression models adjusted for demographics and comorbidities demonstrated that individuals with a pre-existing AID (OR = 1.13, 95% CI 1.09 - 1.17; P< 0.001), IS (OR= 1.27, 95% CI 1.24 - 1.30; P< 0.001), or both (OR = 1.35, 95% CI 1.29 - 1.40; P< 0.001) were more likely to have a life-threatening COVID-19 disease. These results were consistent when evaluating hospitalization. A sensitivity analysis evaluating specific IS revealed that TNF inhibitors were protective against life-threatening disease (OR = 0.80, 95% CI 0.66- 0.96; P=0.017) and hospitalization (OR = 0.80, 95% CI 0.73 - 0.89; P< 0.001). CONCLUSIONS: Patients with pre-existing AID, exposure to IS, or both are more likely to have a life-threatening disease or hospitalization. These patients may thus require tailored monitoring and preventative measures to minimize negative consequences of COVID-19.

Immunogenicity 6 months post COVID-19 mRNA-vaccination among adolescents with juvenile idiopathic arthritis on treatment with TNF-inhibitors.

OBJECTIVES: Mass vaccination is the most effective strategy for controlling the COVID-19 pandemic. This study aimed to evaluate the 6-month immunogenicity after BNT162b2-COVID-19 vaccination in adolescents with JIA on TNFi treatment. METHODS: This single-center study included adolescents with JIA treated with TNFi for at least 18 months. Patients received two doses of COVID-19 vaccine (Pfizer-BioNTech) from April 15th to May 15th 2021. Quantitative measurement of IgG antibodies to SARS-CoV-2-spike-protein-1 was performed at 1,3 and 6 months post-vaccination. RESULTS: Overall, 21 adolescents with JIA in clinical remission at the time of vaccinations were enrolled. None of them discontinued TNFi/MTX treatment at the time of vaccine administration or during the follow-up period. All patients developed a sustained humoral response against SARS-CoV-2 at 1 and 3 months after vaccination (p< 0.05). The antibody levels decreased significantly at 6 months post-vaccination (p< 0.01). The type of JIA did not reveal any differences in the humoral response at 3 (p= 0.894) or 6 months post-vaccination (p= 0.72). No difference was detected upon comparison of the immunogenicity between the different treatment arms (adalimumab vs etanercept) at 3 (p= 0.387) and 6 months (p= 0.526), or TNFi monotherapy vs combined therapy (TNFi plus methotrexate) at 3 (p= 0.623) and 6 months (p= 0.885). CONCLUSIONS: Although mRNA vaccines develop satisfactory immunogenicity at 1- and 3-months post-vaccination in adolescents with JIA on TNFi, SARS-CoV-2 antibody titers decrease significantly overtime, remaining at lower levels at 6 months. Further collaborative studies are required to determine long-term immunogenicity, real duration of immune protection and the need for a booster vaccine dose.

Humoral and cellular immune response to mRNA SARS-CoV-2 BNT162b2 vaccine in adolescents with rheumatic diseases.

BACKGROUND: Data about safety and efficacy of the mRNA SARS-CoV-2 vaccine in adolescents with rheumatic diseases (RD) is scarce and whether these patients generate a sufficient immune response to the vaccine remains an outstanding question. OBJECTIVE: To evaluate safety and humoral and cellular immunity of the BNT162b2 vaccine in adolescents 12 to 18 years with RD and immunosuppressive treatment compared with a healthy control group. METHODS: Adolescents from 12 to 18 years with RD followed at Hospital La Paz in Madrid (n = 40) receiving the BNT162b2 mRNA vaccination were assessed 3 weeks after complete vaccination. Healthy adolescents served as controls (n = 24). Humoral response was measured by IgG antiSpike antibodies, and cellular response by the quantity of IFN-γ and IL-2 present in whole blood stimulated with SARS-CoV-2 Spike and M proteins. RESULTS: There were no differences in spike-specific humoral or cellular response between groups (median IFN-γ response to S specific protein; 528.80 pg/ml in controls vs. 398.44 in RD patients, p 0.78, and median IL-2 response in controls: 635.68 pg/ml vs. 497.30 in RD patients, p 0.22. The most frequent diagnosis was juvenile idiopathic arthritis (26/40, 65%) followed by Lupus (6/40, 15%). 60% of cases (23/40) received TNF inhibitors and 35% (14/40) methotrexate. 40% of patients (26/64) had previous SARS-CoV-2 infection, 9 in the control group and 17 in the RD patients without differences. Of note, 70% of infections were asymptomatic. A higher IFN-γ production was found in COVID-19 recovered individuals than in naive subjects in both groups (controls: median 859 pg/ml in recovered patients vs. 450 in naïve p 0.017, and RD patients: 850 in recovered vs. 278 in naïve p 0.024). No serious adverse events or flares were reported following vaccination. CONCLUSIONS: We conclude that standard of care treatment for adolescents with RD including TNF inhibitors and methotrexate did not affect the humoral and the cellular immunity to BNT162b2 mRNA vaccination compared to a healthy control group. The previous contact with SARS-CoV-2 was the most relevant factor in the immune response.

Subcutaneously-Administered Infliximab in the Management of Rheumatoid Arthritis: A Short Narrative Review of Current Clinical Evidence.

The first subcutaneous (SC) formulation of infliximab CT-P13 has been authorized for the treatment of rheumatoid arthritis (RA) in Europe in 2019. Later, in 2020, approved indications were extended also to ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn's disease (CD) and ulcerative colitis (UC). The present review provides summary of the key features of SC infliximab, with particular focus on pharmacokinetic profile, clinical development program in comparison with the intravenous (IV) formulation, and the latest evidence in the literature. We conclude that SC infliximab represents a new and promising approach in the treatment of patients with RA, offering an optimized clinical profile and a more practical option in comparison to the IV formulation. Nevertheless, SC formulation can improve the use of national health systems resources (e.g., through the time of healthcare workers not having to supervise infusions) and facilitate social distancing measures during the COVID-19 pandemic, as the patient can self-inject the medicine at home without going to the hospital. The limitations of the SC infliximab are mainly due to the limited experience of use in clinical practice and the absence of long-term drug retention data.

Wang-OSO3H catalyzed green synthesis of bioactive isoindolo 2,1-a quinazoline-5,11-dione derivatives: An unexpected observation

The sulphonic acid-functionalized Wang resin (Wang-OSO3H) was explored as a polymeric and recov-erable acidic catalyst for the synthesis of isoindolo[2,1-alpha]quinazoline-5,11-dione derivatives under green conditions. Thus the Wang-OSO3H catalyzed MCR of isatoic anhydride, 2-formylbenzoic acid and vari-ous amines in pure water afforded a range of desired product in good to excellent (86-94%) yield. The methodology can be performed under open air and is amenable for scale-up synthesis. The catalyst can be recovered and recycled for several times without significant loss of its catalytic activity. The unex-pected formation of 2-(1-hydroxy-3-oxoisoindolin-2-yl)benzamide derivative as observed in one case may allow the access of this class of heterocycles from the same MCR by using an appropriate amine. In silico assessment suggested that the compound 4j , a known inhibitor of TNF-alpha could be a potential ligand for SARS-CoV-2 with which it formed H-bonds through its OMe and two C = O groups. (C) 2021 Elsevier B.V. All rights reserved.

Reduced antibody activity against SARS-CoV-2 B.1.617.2 delta virus in serum of mRNA-vaccinated individuals receiving tumor necrosis factor-α inhibitors.

BACKGROUND: Although vaccines effectively prevent coronavirus disease 2019 (COVID-19) in healthy individuals, they appear to be less immunogenic in individuals with chronic inflammatory disease (CID) or receiving chronic immunosuppression therapy. METHODS: Here we assessed a cohort of 77 individuals with CID treated as monotherapy with chronic immunosuppressive drugs for antibody responses in serum against historical and variant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses after immunization with the BNT162b2 mRNA vaccine. FINDINGS: Longitudinal analysis showed the greatest reductions in neutralizing antibodies and Fc effector function capacity in individuals treated with tumor necrosis factor alpha (TNF-α) inhibitors (TNFi), and this pattern appeared to be worse against the B.1.617.2 delta virus. Within 5 months of vaccination, serum neutralizing titers of all TNFi-treated individuals tested fell below the presumed threshold correlate for antibody-mediated protection. However, TNFi-treated individuals receiving a third mRNA vaccine dose boosted their serum neutralizing antibody titers by more than 16-fold. CONCLUSIONS: Vaccine boosting or administration of long-acting prophylaxis (e.g., monoclonal antibodies) will likely be required to prevent SARS-CoV-2 infection in this susceptible population. FUNDING: This study was supported by grants and contracts from the NIH (R01 AI157155, R01AI151178, and HHSN75N93019C00074; NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contracts HHSN272201400008C and 75N93021C00014; and Collaborative Influenza Vaccine Innovation Centers [CIVIC] contract 75N93019C00051).

Clinical Pharmacology Aspects in Patients Treated with TNF Inhibitors During SARS-Cov-2 Pandemic.

In this period of global pandemic caused by SARS-Cov-2, it is of paramount importance to recognize all risk factors that may increase the likelihood of infection. In addition to the risk factors known as pre-existing diseases and old age, risk factors could be drug treatments for chronic diseases, such as immunomodulating drugs that can alter immune defences and response to infectious agents. Antibodies that inhibit tumor necrosis factor (TNF) such as adalimumab infliximab etanercept and golimumab have been used for over 20 years in severe cases of autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease or ankylosing spondylitis. Due to their mechanism of action they reduce inflammation and can stop the progression of the disease by inhibiting a key factor of inflammation such as TNF. In this article we want to examine the possible correlation between therapy with TNF inhibitors and the increased risk of SARS-CoV-2 infection, and the possible paradoxical therapeutic efficacy in patients with ongoing infection, especially in phase two and three. We express our opinion on this very complex and sensitive topic which is the subject of discussion among physicians and experts, based on current knowledge of the literature.

The protective effect of rheumatic disease agents in COVID-19.

Several immunosuppressive therapies have been investigated as potential treatments for patients with severe and critical coronavirus disease 2019 (COVID-19). Notable examples include corticosteroids, interleukin 6 (IL-6), interleukin 1 (IL-1), Janus kinase (JAK), and tumor necrosis factor alpha (TNF-α) inhibitors. The aim of this narrative review is to analyze the mechanistic rationale and available evidence for these selected anti-rheumatic drugs for the treatment of COVID-19. Currently, only corticosteroids have consistently proven to be effective in decreasing mortality and are recommended in clinical guidelines for the treatment of severe and critical COVID-19. Multiple randomized controlled trials (RCTs) are ongoing to determine the role of other immunosuppressants.