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BackgroundJanus kinase inhibitors (JAKinibs) have demonstrated efficacy in the treatment of rheumatoid arthritis (RA) and spondyloarthritis (SpA), although their safety profile continues to be analysed due to the possible increase in adverse events (AEs) in relation to anti-TNFs (mild and severe infections, haematological alterations, thromboembolism, increase in neoplasms).ObjectivesTo evaluate in real clinical practice the AEs of JAKinibs in a cohort of patients with RA and SpA. In addition, adherence and reasons for discontinuation (1st or 2nd failure, AE) are analysed.MethodsObservational study of 116 patients diagnosed with RA or SpA who received treatment with JAKinibis (tofacitinib, baricitinib, upadacitinib) after failure of treatment with different classical synthetic (FAMEsc) or biological (FAMEb) disease-modifying drugs. The following data were analysed: demographic characteristics of the patients, years of disease progression, 1st or 2nd failures and AE.ResultsMean age was 52 years, with Baricitinib being older (60 years -SD 13.6), higher prevalence of females in all groups, and a disease progression time of about 10 years. Mean number of FAMEsc was 1.6 and mean number of FAMEb was 2,3 to Tofacitinib(Tofa), 2,76 to Baricitinib(Bari) and 4,4 to Upadacitinib(Upa). 71 (63%) patients had active corticosteroid therapy. The median treatment time with Tofa was 8.8 months, Bari 9.5 and Upa 2.4 months.Most frequent AEs with Tofa were urinary tract infections(UTI) (11.9%, 7 cases) and headaches (8.47%, 5 cases). There were 3 cases of herpes zoster (5.1%), one of which was recurrent, and 2 cases respectively of tachycardia and gastrointestinal intolerance (3.4%). With Baricitnib, 2(5%) cases of UTI and 2(5%) of influenza A were reported. Most frequent AEs related to Upadacitinb are gastrointestinal intolerance, labialis and facial herpes, anterior uveitis and recurrent UTI, with 1 case for each adverse event. There were 4 success with Baricitinib treatment: 2 due to severe COVID, 1 influenza A and 1 due to stroke. 17 patients had 1st failure to Tofa(28.81%), 8 to Bari20.0%) and 3 to Upa(18.75%);7(11.86%) and 2(5%) patients had 2nd failure to Tofa and Bari respectively, no with Upa.Mean CRP to Tofa-SD 18.9-was 17.19, 20-SD 22.7- to Bari and 24.2-SD 27.40- to Upa. Mean ESR-SD 15.3- was 25.4, -SD 26.4 and 44.3 -SD 32-, respectively. At 6 months, 36(62%) were continuing on Tofa, 22(56%) on Bari and 4(27%) on Upa. At 12 months, 27(46.6%) were still on Tofa and 12 on Bari(30.8%) and no patients were on upa.Table 1.TofaBariUpaMean age496047Male19%18%20%Female81%82%80%Time course of disease(years)81111Permanence 6 months62%56%27%Permanence 12 months46,6%31%0%Patients with corticotherapy62%64%60%Previous biological drugs2,3 SD 22,8 SD 2,34,4 SD 2,9Patients who discontinued the drug62%59%33%Mean CRP at the end of treatment172024Mean end-of-treatment ESR252644Repeated AEsUTI(7) Headache(5) Shingles(3) Nephritic colic(2) Gastrointestinal intolerance(2) Tachycardia(2)UTI(4) Headache(2)Serious AEsShingles (3)Varicella encephalopathy(1) Stroke(1) Shingles (1)1st failure28,8%20%18,7%2nd failure11,9%5%0%SuccessSARS-Cov2(2) Influenza(1) Stroke(1)Figure 1. Months stay pharmacoConclusionMost frequent adverse events with JAKinibs are mild infections, except gastrointestinal complaints with upadacitinib. Serious adverse events, including 3 deaths from viral infections, were observed, mostly in patients over 65 years. Most frequent cause of discontinuation was treatment failure. We believe that further observational studies are needed to stratify and profile the risk of infection with JAKinibs.References[1]Atzeni F, Popa CD, et al. Safety of JAK inhibitors: focus on cardiovascular and thromboembolic events. Expert Rev Clin Immunol. 2022 Mar;18(3):233-244. Doi: 10.1080/1744666X.2022.2039630 Epub 2022 Feb 17.PMID: 35129033[2]Alves C, Penedones A,et al. The Risk of Infections Associated With JAK Inhibitors in Rheumatoid Arthritis: A Systematic Review and Network Meta-analysis. J Clin Rheumatol. 2022 Mar 1;28(2):e407-e414 PMID:33902098Ackn wledgements:NIL.Disclosure of InterestsNone Declared.
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Background: Tenofovir-based daily oral HIV pre-exposure prophylaxis (HIV PrEP) is a highly efficacious HIV prevention modality, but sustained use over time is needed for continued protection among individuals at high risk for HIV exposure. Suboptimal adherence and retention in care threaten to diminish the impact of HIV PrEP on reducing HIV burden. PrEP PERU is an ongoing, multi-site, prospective cohort study evaluating HIV PrEP implementation among adult men who have sex with men (MSM) and transgender women (TGW) accessing care at non-government health centers in Peru. We sought to evaluate HIV PrEP adherence and retention in care among PrEP PERU participants prior to the onset of COVID-19 service disruptions. Method(s): We analyzed baseline and follow-up data from the PrEP PERU study through 3/15/2020, the first day of Peru's COVID-19 lockdown. MSM and TGW >=18 years of age with at least one HIV risk factor were eligible for enrollment. After the first follow-up visit at 4 weeks, TDF/FTC refills and clinic visits occur quarterly, at the discretion of the prescribing clinician. The medication is provided free of charge, but participants pay for laboratory testing plus a small service fee for clinic visits. Data is collected at baseline and quarterly follow-up visits on sexual risk behaviors and HIV PrEP use. We used bivariate analysis to evaluate the association between baseline factors and 6-month HIV PrEP retention in care. As a proxy for adherence, pharmacy dispensation records were used to calculate the proportion of days covered (PDC) by TDF/FTC. Result(s): Overall, 351 participants started TDF/FTC at four study sites in Lima from 1/23/2017 to 3/15/2020. Of this analysis population, 94% were cisgender men, 10% identified as bisexual, and median age was 31 (interquartile range [IQR], 27 - 38). Among those with at least 6 months of observation time (n=302), 91% attended >=1 follow-up visit and 77% attended >=2 follow-up visits during the 6 months after enrollment. The proportion with favorable adherence (PDC >=0.8) was 85%. There were 6 confirmed HIV seroconversions in the analysis period (1.2 per 100 person-years). Conclusion(s): In this analysis of HIV PrEP outcomes among MSM and TGW prior to COVID-19 pandemic disruptions in Peru, over 3/4 of the population remained in care and had favorable measures of adherence during the first 6 months after.
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TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: An acute respiratory syndrome associated to the novel coronavirus SARS-CoV-2 has affected the entire world. Pediatric patients can rarely present with a severe complication identified as multisystem inflammatory syndrome in children (MIS-C).(1) After its recognition by the CDC and media reports of young adults with the same syndrome, a series of cases in adults (MIS-A) was published in late 2020.(2) CASE PRESENTATION: A 25-year-old Hispanic male who tested positive for SARS-CoV-2 by RT-PCR six weeks prior presented to the emergency department with one week of sore throat, fever, non-bloody diarrhea, conjunctivitis, and mild confusion. On examination, the patient was febrile, had tender submandibular lymph nodes and redness on the oropharynx. Initial laboratory results showed systemic inflammation. COVID-19 RT-PCR test was negative, coronavirus IgG was positive, and chest radiograph was normal. On the third day, the patient's clinical status deteriorated despite antibiotic use with hypotension and hypoxemia requiring vasopressor support and ICU admission. An echocardiogram showed left ventricular ejection fraction (EF) of 35% with hypokinesia. Due to persistent shock state and elevated inflammatory markers after 36 hours, we started him on methylprednisolone 1.5 mg/kg daily. After 24 hours, clinical status and inflammatory markers improved significantly. A follow-up echocardiogram four weeks after discharge showed normalization of EF. DISCUSSION: Since the beginning of the pandemic, different countries reported cases of a hyperinflammatory process in children that had features similar to atypical Kawasaki disease.(3) A larger study described MIS-C in 99 patients under 21 years of age in New York.(4) The case definition MIS-C was established by the CDC. For a time, it was unknown if this syndrome was specific to children or whether it also occurred in adults. A MIS-A working case definition includes five criteria: severe illness requiring hospitalization in a person aged at least 21 years;a positive test result for current or previous SARS-CoV-2 infection;severe dysfunction of one or more extrapulmonary organ systems;laboratory evidence of severe inflammation;and absence of severe respiratory illness.(2) Case definitions for MIS-C/A with degrees of diagnostic certainty have also been elaborated.(5) We are presenting a patient that meets clinical and laboratory criteria for MIS-A. His respiratory dysfunction occurred after admission when his inflammatory markers were already elevated. This case includes a temporal correlation after the initial peak of COVID-19 cases in Houston by 31 days. CONCLUSIONS: The number of cases of MIS-A is unclear. It is important to keep this condition in our differential in the context of recent SARS-CoV-2 infection for early identification and appropriate treatment to reduce further harm and mortality. REFERENCE #1: 1. Centers for Disease Control and Prevention. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19). Published online May 14, 2020. Accessed April 22, 2020. https://emergency.cdc.gov/han/2020/han00432.asp2. Morris SB, Schwartz NG, Patel P, et al. Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection — United Kingdom and United States, March–August 2020. MMWR Morb Mortal Wkly Rep. 2020;69(40):1450-1456. doi:10.15585/mmwr.mm6940e1 REFERENCE #2: 3. Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. The Lancet. 2020;395(10239):1771-1778. doi:10.1016/S0140-6736(20)31103-X4. Dufort EM, Koumans EH, Chow EJ, et al. Multisystem Inflammatory Syndrome in Children in New York State. N Engl J Med. 2020;383(4):347-358. doi:10.1056/NEJMoa2021756 REFERENCE #3: 5. Vogel TP, Top KA, Karatzios C, et al. Multisystem inflammatory syndrome in children and adults (MIS-C/A): Case definition & guidelines for data collectio , analysis, and presentation of immunization safety data. Vaccine. Published online February 2021:S0264410X21000931. doi:10.1016/j.vaccine.2021.01.054 DISCLOSURES: No relevant relationships by Luis Chug, source=Web Response No relevant relationships by Julin Mathew, source=Web Response No relevant relationships by Nora Moron Cabrera, source=Web Response No relevant relationships by Rohini Rao, source=Web Response No relevant relationships by Juan Salvatierra, source=Web Response