Infection may play an important role in the pathogenesis of alveolar osteonecrosis following facial herpes zoster: a case report and literature review.

BACKGROUND: Herpes zoster (HZ) is one of the most common skin diseases caused by viruses. Facial HZ develops when the varicella-zoster virus affects the trigeminal nerve, and alveolar osteonecrosis is a rare complication. However, the exact pathogenesis of postherpetic alveolar osteonecrosis remains unclear. CASE DESCRIPTION: We encountered a patient who presented to the dermatology clinic with facial HZ and tooth exfoliation in the upper right jaw, and panoramic radiography revealed decreased bone density and poor alveolar socket healing in his right maxilla. Biopsy of the alveolar process revealed fragments of nonvital lamellar bone, which were devoid of osteoblasts and osteocytes and were surrounded by numerous neutrophils and bacterial aggregates. Thus, the diagnosis of alveolar osteonecrosis following facial HZ was confirmed. He then underwent resection of the osteonecrotic tissue. The pathological findings of postoperative tissue were similar to those of previous biopsies. Varicella-zoster virus and multiple types of bacteria were detected through next-generation sequencing, and the species of bacteria were consistent with the results of bacterial culture. Antibiotics and valaciclovir were administered during the perioperative period. The patient showed good recovery at the 9-month follow-up. CONCLUSIONS: The coexistence of bacterial and viral infection may play an important role in the pathogenesis of alveolar osteonecrosis following HZ. To our knowledge, we are the first to directly explore microbial pathogens in a case of postherpetic alveolar osteonecrosis through next-generation sequencing and bacterial culture. We recommend that oral examinations be carefully conducted for patients who are diagnosed with facial HZ, even if their facial rashes have faded away. We suggest that a prolonged and full-dose antiviral therapy course may be beneficial for the treatment of facial HZ with intraoral lesions. The implementation of dental preventive measures should be considered for patients with facial HZ. The application of antibiotics and excision of necrotic bone may reduce the abundance of bacteria in lesions and improve wound healing.

Management of Oral Manifestations of Herpes Simplex Virus, Varicella Zoster Virus, and Human Papillomavirus.

Human herpes virus is a family of DNA viruses that includes herpes simplex virus (HSV) and varicella zoster virus (VZV). HSV-1 and HSV-2 are fairly common and result in oral and genital lesions. Recurrent infections of herpes include lesions on the lips resulting in pain and possibly societal stigma, making adequate treatment of these conditions crucial. VZV is the cause of chicken pox and shingles. Acyclovir and other nucleoside analogues have been the gold standard of treatment for HSV and VZV, but newer, more effective treatments are being developed, which is beneficial regarding the issue of resistance to standard antivirals. Human papillomavirus (HPV) is also a DNA virus with different subtypes that result in four common oral benign lesions. The significance and treatments of HSV, VZV, and HPV are discussed, along with certain developing treatments of herpes labialis (HSV).

[Left mandibular osteonecrosis following herpes zoster of the third branch of left trigeminal nerve: A case report].

Herpes zoster of trigeminal nerve was a common skin disease caused by varicella-zoster virus infection. Simple involvement of the third branch of trigeminal nerve was rare, and so were oral complications such as pulpitis, periodontitis, spontaneous tooth loss, bone necrosis, etc. This article presented a case of herpes zoster on the third branch of the left trigeminal nerve complicated with left mandibular osteonecrosis. We reported the case of a 64-year-old man with sudden pain in the left half of the tongue 1 month ago, and then herpes on the left facial skin appeared following with acute pain.The local hospital diagnosed it as herpes zoster and treated it with external medication. A few days later, he developed gum pain in the left mandibular posterior tooth area. He was admitted to Peking University School and Hospital of Stomatology one week ago with loose and dislodged left posterior tooth accompanied by left mandibular bone surface exposure. Clinical examination showed bilateral symmetry and no obvious restriction of mouth opening. Visible herpes zoster pigmentation and scarring on the left side of the face appeared. The left mandibular posterior tooth was missing, the exposed bone surface was about 1.5 cm×0.8 cm, and the surrounding gingiva was red and swollen, painful under pressure, with no discharge of pus. The remaining teeth in the mouth were all Ⅲ degree loosened. Imageological examination showed irregular low-density destruction of the left mandible bone, unclear boundary, and severe resorption of alveolar bone. The patient was diagnosed as left mandibular osteonecrosis. Under general anesthesia, left mandibular lesion exploration and curettage + left mandibular partial resection + adjacent flap transfer repair were performed. The patient was re-exmained 6 months after surgery, there was no redness, swelling or other abnormality in the gums and the herpes pigmentation on the left face was significantly reduced. Unfortunately, the patient had complications of postherpetic neuralgia. This case indicate that clinicians should improve their awareness of jaw necrosis, a serious oral complication of trigeminal zoster, and provide early treatment. After the inflammation was initially controlled, surgical treatment could be considered to remove the necrotic bone, curettage the inflammatory granulation tissue, and extraction of the focal teeth to avoid further deterioration of the disease.

Pandemic antecedents - Exploring predictivity and relationships between COVID-19 vaccine uptake and influenza, shingles, and HPV vaccination.

BACKGROUND: A wealth of extant research focuses on identifying barriers to, and predictors of, COVID-19 vaccination. In addition to treating COVID-19 vaccination and related experiences as antecedents, this study analyzes the relationships between COVID-19 vaccination experiences and intent to receive the flu, shingles, and HPV vaccines. METHOD: Analyses were performed on the responses from U.S. survey panel of 1,024 participants (n = 1,024), 530 (51.8 %) who received at least a dose of the COVID-19 vaccine and 494 (48.2 %) who had not. Descriptive and inferential statistics identify participant demographic characteristics, prior vaccination behavior, vaccination intentions, risk behavior assessment, vaccination attitudes and beliefs, and the predictivity of COVID-19 vaccination, when treated as an antecedent. RESULTS: Receiving a first dose of the COVID-19 vaccine interacted with receiving a past influenza vaccine, predicting the future intention to receive a COVID-19 vaccine or booster. Vaccine hesitancy in parents is significantly related to vaccination behaviors for themselves and their children. Analyses also showed differences between the vaccinated group (VG) and the unvaccinated group (UVG) on hesitancy, beliefs, and attitudes toward the COVID-19 vaccine. CONCLUSION: Experience with COVID-19 vaccination and the relationship of those experiences with other vaccinations provide useful insight on leveraging vaccine uptake. Healthcare professionals should improve the COVID-19 vaccination experience and use vaccination appointments to promote other vaccinations. Research should continue to compare vaccination experiences and how they may persuade or dissuade vaccination intent for other vaccinations.

[Risk Factors and the Effect of Antiviral Prophylaxis for Herpes Zoster in Multiple Myeloma Patients].

OBJECTIVE: To study the incidence and risk factors of herpes zoster in patients with multiple myeloma and to evaluate the preventive effect of antiviral therapy. METHODS: The clinical features of multiple myeloma patients with herpes zoster were retrospectively analyzed, the risk factors of herpes zoster and the effect of antiviral prophylaxis were analyzed. RESULTS: Among 180 patients with multiple myeloma, 23 cases developed herpes zoster (12.8%). The incidence of herpes zoster was 19.1% in patients with renal dysfunction and 23.5% after autologous hematopoietic stem cell transplantation (ASCT). The incidence of herpes zoster was higher in patients receiving bortezomib-containing regimens (21/137, 15.3%) than that in those without bortezomib (2/43, 4.7%), but there was no statistical difference (P =0.067). Antiviral prophylaxis was associated with fewer zoster infections, 8/111(7.2%) developed herpes zoster in patients who received antiviral prophylaxis, and 15/69 (21.7%) in those receiving no prophylaxis(P =0.005). 65.2% of patients with herpes zoster did not receive antiviral prophylaxis. Multivariate analysis showed that bortezomib treatment, AHSCT and renal dysfunction were independent risk factors for multiple myeloma with herpes zoster, while antiviral prophylaxis was independently associated with reducing the risk of herpes zoster. Herpes zoster had no effect on OS in patients with multiple myeloma. CONCLUSION: The risk of herpes zoster in multiple myeloma patients was increased. Antiviral prophylaxis can reduce the risk of herpes zoster in patients on bortezomib-based therapy.

Crohn's Disease and Herpes Zoster: Being Mindful of Vaccination.

Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract. Immunosuppressive therapy is the main treatment modality in Crohn's disease. Herpes zoster (HZ), caused by Varicella-zoster virus, is a relatively common albeit burdensome clinical picture mainly affecting adult population with immunosuppressive status. In this paper, we aimed to report a Crohn's disease patient with HZ to raise awareness on vaccination. There are commercially available vaccines that are shown to be safe and effective against HZ reactivation. Crohn's disease patients should be evaluated and informed about preventive options against HZ to prevent unwanted HZ-related complications.

Hospitalizations of patients with herpes zoster in Poland during 2012-2021: A population-based study.

INTRODUCTION: The varicella-zoster virus (VZV) is an infectious agent that causes both chickenpox and herpes zoster/shingles (HZ). This infection can take various clinical forms, result in permanent complications, and be a marker of immunosuppression, e.g. in the course of a neoplastic disease. The aim of this study is to analyze epidemiological trends in hospitalization and hospital mortality rate among HZ patients in Poland (2012-2021). METHODS: Our study is a population-based, retrospective analysis of hospital discharge records of patients with HZ. Data were obtained from the National Institute of Public Health in Poland, and they covered the period from 2012 to 2021. All hospitalization records with primary or secondary ICD-10 B02 code diagnosis were included in the study. RESULTS: We analyzed the total number of 23,432 hospital discharge records of HZ patients in 2012-2021. The study group consisted of 22,169 (94.6 %) hospitalization records of first-time diagnosis of HZ in hospitalized patients: 9,309 males (42 %) and 12,860 females (58 %). In this group, 70.3 % were patients over 60 years old. The mean and median age was 64 and 69 years, respectively. The mean annual first-time hospitalization rate for HZ was estimated to be 5.8 per 100,000 person-years (95 % CI: 4.8-6.7 per 100,000 person-years). The hospitalization rate for HZ was similar during 2012-2019. There was a significant decrease in hospitalizations in 2020-2021 in comparison with the previous years (R2 = 0.42, p < 0.05). Women showed a higher hospitalization rate than men (p < 0.001). Urban residents had a higher hospitalization rate than rural residents (p < 0.001). In the analyzed period, 246 deaths were recorded (1.1 % of all hospitalized HZ patients) -119 males and 127 females. CONCLUSIONS: The HZ-related number of hospitalizations and mortality in Poland are relatively low, but HZ is still a significant health problem. Risk factors include female gender, older age and residence in urban areas.

Tofacitinib use in ulcerative colitis: An expert consensus for day-to-day clinical practice.

Rising number of inflammatory bowel disease (IBD) cases in developing countries necessitate clear guidance for clinicians for the appropriate use of advanced therapies. An expert consensus document was generated to guide the usage of tofacitinib, a Janus kinase inhibitor, in ulcerative colitis. Tofacitinib is a useful agent for the induction and maintenance of remission in ulcerative colitis. It can be used in the setting of biological failure or even steroid-dependent and thiopurine refractory disease. Typically, the induction dose is 10 mg BD orally. Usually, clinical response is evident within eight weeks of therapy. In those with clinical response, the dose can be reduced from 10 mg BD to 5 mg BD. Tofacitinib should be avoided or used cautiously in the elderly, patients with cardiovascular co-morbidity, uncontrolled cardiac risk factors, previous thrombotic episodes and those at high risk for venous thrombosis or previous malignancy. Baseline evaluation should include testing for and management of hepatitis B infection and latent tuberculosis. Where feasible, it is prudent to ensure complete adult vaccination, including Herpes zoster, before starting tofacitinib. The use of tofacitinib may be associated with an increased risk of infections such as herpes zoster and tuberculosis reactivation. Maternal exposure to tofacitinib should be avoided during pre-conception, pregnancy, and lactation. There is emerging evidence of tofacitinib in acute severe colitis, although the exact positioning (first-line with steroids or second-line) is uncertain.

Real-World Coverage With Influenza, Pneumococcal, and Herpes Zoster Vaccines Among Patients With Rheumatic Diseases in a Nationwide Healthcare Plan.

OBJECTIVE: Vaccination against preventable infections is important for the management of rheumatic diseases (RDs). This study assessed the vaccination coverage and predictors among patients with RDs using real-world data from Israel. METHODS: This retrospective cross-sectional study, based on a Maccabi Healthcare Services database, included adult patients diagnosed with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and systemic lupus erythematosus (SLE), as of April 30, 2019. Age-specific vaccination coverage for influenza (past year), pneumococcal (23-valent pneumococcal polysaccharide vaccine [PPSV23] and/or 13-valent pneumococcal conjugate vaccine [PCV13]), and live-attenuated herpes zoster (HZ) vaccines (past 5 years) was reported. Logistic regression was used to investigate predictors of vaccination. RESULTS: The study included 14,528 patients (RA: n = 6932; PsA: n = 4395; SLE: n = 1951; > 1 condition: n = 1250). Influenza vaccine coverage among patients with RA, PsA, and SLE was 45.1%, 36.2%, and 33.7%, respectively. For PPSV23, corresponding rates were 19.6%, 16.2%, and 12.6%, respectively. In the elderly population (≥ 65 years), 63.2% had influenza vaccine in the past year and 83.4% had a PPSV23 vaccine in the past 5 years or at age ≥ 65. For PCV13 and HZ, coverage in the overall study population was low at 4.8% and 3.6%, respectively. Central residence and treatment with corticosteroids and biologic or targeted synthetic disease-modifying antirheumatic drugs within the past 5 years were significant predictors of vaccination coverage across all vaccines (P < 0.05). Other predictors varied by vaccine, including female sex (influenza, PPSV23, PCV13), age (influenza, PPSV23), chronic comorbidities (influenza, PPSV23, PCV13), shorter disease duration (PCV13), and high socioeconomic status (PCV13, HZ). CONCLUSION: This study demonstrated suboptimal coverage of influenza, pneumococcal, and HZ vaccination in patients with RA, PsA, and SLE, in particular among younger adults in Israel.

BioNTech COVID-19 (BNT162b2) Vaccination and Varicella Zoster Reactivation: A Comprehensive Cross-sectional Study.

Herpes zoster (HZ) results from reactivation of latent varicella-zoster virus. Recent observations have suggested that HZ is associated with vaccination against COVID-19. To investigate the association between the vaccine and HZ severity, a single-centre, cross-sectional study of all patients diagnosed with HZ and 2 control diagnoses (cellulitis and bone fractures), between 2017 and 2021, was performed. Hospital visits and hospitalization rates were compared. All medical records of patients diagnosed with HZ in the first year after the COVID-19 vaccination campaign began were reviewed, in order to generate a retrospective cohort comparing vaccinated and unvaccinated patients with HZ. All participants had received the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine. During the study period, 2,413 patients were diagnosed with HZ, and when normalized to control diagnoses the number of cases remained stable. The retrospective cohort included 365 patients. A multivariate analysis controlling for sex, age, autoimmune diseases, malignancies, and immunosuppressive therapy showed higher admission rates in vaccinated compared with unvaccinated individuals (odds ratio (OR) 2.75, 95% CI 1.27-5.96, p = 0.01). However, matching techniques and stratification by age, used to better control for confounders, invalidated these findings. No differences were observed in other variables indicative of disease severity (hospital stay length and complications). In conclusion, COVID-19 vaccination was not found to be associated with an increased risk of HZ-related admission and complications.

A Rare Case of Varicella Zoster Infection in Hemorrhoids in a Patient With Inflammatory Bowel Disease.

ABSTRACT: Hemorrhoids are normal anatomical structures in the anus. When symptomatic, they prompt medical attention due to pain, rectal bleeding, and discomfort. Treatment includes dietary modifications, rubber band ligations, sclerotherapy, cryotherapy, or hemorrhoidectomy. Histologic examination is important to rule out incidental findings, such as perianal intraepithelial neoplasia, anal carcinoma, melanoma, or coexisting infections. Special attention should be given when patient is immunocompromised. We present a case of a 41-year-old man with a history of ulcerative colitis on adalimumab who presented with anal lesions. He was diagnosed with hemorrhoids and surgically treated. Microscopic examination confirmed the diagnosis of hemorrhoids. However, foci of epithelium with viral cytopathic effects were noted. A varicella zoster virus (VZV)-specific immunostain was positive in the areas of interest confirming the diagnosis of the VZV infection limited to the hemorrhoids. Combined herpes simplex virus type 1 and 2 (HSV 1 and HSV 2) immunostain was also performed and was negative. Anal herpes has been widely described in the literature, particularly in immunocompromised patients. However, isolated VZV infection in hemorrhoids to the best of our knowledge has never been reported.

Herpes zoster after the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in actively treated cancer patients: a prospective study.

Several concerns have been raised about a causal relationship between COVID-19 mRNA-based vaccines and the development of herpes zoster (HZ). We performed a prospective analysis of the Vax-On-Third-Profile study to investigate the incidence of HZ after the third dose of mRNA-BNT162b2 (tozinameran) and its correlation with immune responses. Patients who had received a booster dose and had been actively treated for at least 8 weeks were eligible. Serologic assessment was performed before the third dose of tozinameran (timepoint-1) and 4 weeks later (timepoint-2). We also assessed the incidence of SARS-CoV-2 breakthrough infections at predefined time points. The current analysis included 310 patients, of whom 109 (35.2%) and 111 (35.8%) were being treated with targeted therapies and cytotoxic chemotherapy, respectively. All participants received a third dose of tozinameran between September 26 and October 30, 2021. After a mean follow-up of 17.3 (IQR 15.1-18.4) months, HZ occurred in 8 recipients, for a cumulative incidence of 2.6%, and an incidence rate of 0.310 per person-year (95% CI 0.267-0.333). All HZ cases occurred within 30 days of booster dosing (range 5-29 days), with a median time to onset of 15 (IQR 9-22) days. Among the 7 patients (2.2%) who also contracted a SARS-CoV-2 infection, all cases preceded COVID-19 outbreaks. No instances of complicated HZ were reported. In multivariate analysis, impaired T helper and T cytotoxic cell counts independently correlated with HZ occurrence. These findings provide the first evidence that cancer patients on active treatment have a not negligible risk of developing HZ within 30 days after the third dose of tozinameran. The favorable clinical outcome of all observed cases confirms that protective effects of boosters in reducing the risk of severe COVID-19 outweigh the potential risk of HZ occurrence.

Rare Combination of Abducens Nerve Palsy and Optic Neuritis on the Same Side: Case Report and Review of 8 Patients in Literature.

The concurrent development of abducens nerve palsy and optic neuritis on the same side is rare. Here we presented an 82-year-old man who developed the combination of abducens nerve palsy and optic neuritis on the left side 2 months after the sixth inoculation of COVID-19 mRNA vaccine. In past history at 45 years old, he experienced subarachnoid hemorrhage and underwent surgery for the clipping of intracranial aneurysm. The patient had no systemic symptoms, such as general fatigue, fever, arthralgia, and skin rashes. Physical and neurological examinations were also unremarkable. Since the aneurysmal metal clip used at that time was not compatible with magnetic resonance imaging, he underwent computed tomographic (CT) scan of the head and showed no space-occupying lesion in the orbit, paranasal sinuses, and brain. As an old lesion, the anterior temporal lobe on the left side had low-density area with metallic artifact on the left side of the skull base, indicative of metal clipping. In 4 weeks of observation from the initial visit, he showed complete recovery of visual acuity and became capable of abducting the left eye in full degrees. We also reviewed 8 patients with the combination of abducens nerve palsy and optic neuritis in the literature to reveal that the combination of signs did occur in mild meningitis with rare infectious diseases and in association with preceding herpes zoster in the first branch of the trigeminal nerve. The course of the present patient suggested that the combination of signs might be vaccine-associated.

Impaired STING Activation Due to a Variant in the E3 Ubiquitin Ligase AMFR in a Patient with Severe VZV Infection and Hemophagocytic Lymphohistiocytosis.

Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus exclusively infecting humans, causing two distinct pathologies: varicella (chickenpox) upon primary infection and herpes zoster (shingles) following reactivation. In susceptible individuals, VZV can give rise to more severe clinical manifestations, including disseminated infection, pneumonitis, encephalitis, and vasculopathy with stroke. Here, we describe a 3-year-old boy in whom varicella followed a complicated course with thrombocytopenia, hemorrhagic and necrotic lesions, pneumonitis, and intermittent encephalopathy. Hemophagocytic lymphohistiocytosis (HLH) was strongly suspected and as the condition deteriorated, HLH therapy was initiated. Although the clinical condition improved, longstanding hemophagocytosis followed despite therapy. We found that the patient carries a rare monoallelic variant in autocrine motility factor receptor (AMFR), encoding a ubiquitin ligase involved in innate cytosolic DNA sensing and interferon (IFN) production through the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway. Peripheral blood mononuclear cells (PBMCs) from the patient exhibited impaired signaling downstream of STING in response dsDNA and 2'3'-cGAMP, agonists of cGAS and STING, respectively, and fibroblasts from the patient showed impaired type I IFN responses and significantly increased VZV replication. Overexpression of the variant AMFR R594C resulted in decreased K27-linked STING ubiquitination compared to WT AMFR. Moreover, ImageStream technology revealed reduced STING trafficking from ER to Golgi in cells expressing the patient AMFR R594C variant. This was supported by a dose-dependent dominant negative effect of expression of the patient AMFR variant as measured by IFN-ß reporter gene assay. Finally, lentiviral transduction with WT AMFR partially reconstituted 2'3'-cGAMP-induced STING-mediated signaling and ISG expression in patient PBMCs. This work links defective AMFR-STING signaling to severe VZV disease and hyperinflammation and suggests a direct role for cGAS-STING in the control of viral infections in humans. In conclusion, we describe a novel genetic etiology of severe VZV disease in childhood, also representing the first inborn error of immunity related to a defect in the cGAS-STING pathway.

Variation in Receipt of Cancer Screening and Immunizations by 10-year Life Expectancy among U.S. Adults aged 65 or Older in 2019.

IMPORTANCE: The likelihood of benefit from a preventive intervention in an older adult depends on its time-to-benefit and the adult's life expectancy. For example, the time-to-benefit from cancer screening is >10 years, so adults with <10-year life expectancy are unlikely to benefit. OBJECTIVE: To examine receipt of screening for breast, prostate, or colorectal cancer and receipt of immunizations by 10-year life expectancy. DESIGN: Analysis of 2019 National Health Interview Survey. PARTICIPANTS: 8,329 non-institutionalized adults >65 years seen by a healthcare professional in the past year, representing 46.9 million US adults. MAIN MEASURES: Proportions of breast, prostate, and colorectal cancer screenings, and immunizations, were stratified by 10-year life expectancy, estimated using a validated mortality index. We used logistic regression to examine receipt of cancer screening and immunizations by life expectancy and sociodemographic factors. KEY RESULTS: Overall, 54.7% of participants were female, 41.4% were >75 years, and 76.4% were non-Hispanic White. Overall, 71.5% reported being current with colorectal cancer screening, including 61.4% of those with <10-year life expectancy. Among women, 67.0% reported a screening mammogram in the past 2 years, including 42.8% with <10-year life expectancy. Among men, 56.8% reported prostate specific antigen screening in the past two years, including 48.3% with <10-year life expectancy. Reported receipt of immunizations varied from 72.0% for influenza, 68.8% for pneumococcus, 57.7% for tetanus, and 42.6% for shingles vaccination. Lower life expectancy was associated with decreased likelihood of cancer screening and shingles vaccination but with increased likelihood of pneumococcal vaccination. CONCLUSIONS: Despite the long time-to-benefit from cancer screening, in 2019 many US adults age >65 with <10-year life expectancy reported undergoing cancer screening while many did not receive immunizations with a shorter time-to-benefit. Interventions to improve individualization of preventive care based on older adults' life expectancy may improve care of older adults.

Safety of the JAK and TNF inhibitors in rheumatoid arthritis: real world data from the Hong Kong Biologics Registry.

OBJECTIVES: To compare the incidence of major adverse cardiovascular events (MACEs), cancer and infective complications in RA patients using Janus kinase (JAKis) and TNF (TNFis) inhibitors. METHOD: A retrospective analysis of data from the Hong Kong Biologics Registry 2008-2021 was performed. RA patients who had ever used JAKis or TNFis were included. The incidence of MACEs, cancer and infections were compared between the two groups, with adjustment for confounding factors. RESULTS: A total of 2471 courses of JAKis (n = 551) and TNFis (n = 1920) were used in 1732 RA patients (83.7% women, age 53.8 [12.5] years; follow-up 6431 patient-years). JAKi users had significantly older age, more atherosclerotic risk factors and higher frequency of past malignancies. A total of 15 and 40 MACEs developed in the JAKi and TNFi users, respectively (incidence 1.34 vs 0.75 per 100 patient-years; P = 0.22). There was no significant difference in the incidence of cancers between the two groups (0.81 [JAKi] vs 0.85 [TNFi] per 100 patient-years; P = 0.25). The adjusted hazard ratios of MACE and cancer in the JAKi users were 1.36 (95% CI: 0.62, 2.96) (P = 0.44) and 0.87 (95% CI: 0.39, 1.95) (P = 0.74), respectively. Rates of infections were significantly higher in the JAKi than TNFi users (16.3 vs 9.9 per 100 patient-years; P = 0.02), particularly herpes zoster (3.49 vs 0.94 per 100 patient-years; P < 0.001). CONCLUSIONS: In a real-life setting, there is no increase in MACEs or cancers in users of JAKis compared with TNFis. However, the incidence of non-serious infections, including herpes zoster, was increased in users of JAKis.