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The coronavirus disease 2019 (COVID-19) pandemic is caused by rapid spread of different strains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The severity of infection ranges from mild, or even asymptomatic, to very severe. Signs and symptoms include fatigue, fever, exanthemas, upper respiratory illness, loss of smell and taste, pneumonia, severe acute respiratory syndrome, and multi-organ failure. Risk factors for a severe or lethal course include age, male gender, obesity, diabetes, cardiovascular disease, and immune suppression1 .

Background Janus kinase (JAK) inhibition is a new mode of action in atopic dermatitis (AD); clarity about drug class safety considerations in the context of AD is important. Baricitinib, an oral, reversible, selective inhibitor of JAK1/JAK2, is in late-stage development for adult patients with moderate-to-severe AD. Objective To report pooled safety data for baricitinib in patients with moderate-to-severe AD in the clinical development program including long-term extension (LTE) studies. Methods This analysis included patient-level safety data from six double-blinded, randomized, placebo-controlled studies (one phase 2 and five phase 3), one double-blinded, randomized, LTE study and one open-label LTE study, reported in three data sets: placebo-controlled, 2-mg - 4-mg extended and All-bari AD. Safety outcomes include treatment-emergent adverse events, adverse events of special interest and abnormal laboratory changes. Proportions of patients with events and incidence rates were calculated. Results Data were collected for 2531 patients who were given baricitinib for 2247 patient-years (median duration 310 days). The frequency of serious infections, opportunistic infections and conjunctival disorders was low and similar between treatment groups in the placebo-controlled period. The most common serious infections were eczema herpeticum [n = 11, incidence rates (IR) = 0.5], cellulitis (n = 6, IR = 0.3) and pneumonia (n = 3, IR = 0.1). There were four opportunistic infections (IR = 0.2). No malignancies, gastrointestinal perforations, positively adjudicated cardiovascular events or tuberculosis were reported in the placebo-controlled period in baricitinib-treated patients. Frequency of herpes simplex was higher in the 4-mg group (6.1%) vs. the 2-mg (3.6%) and placebo group (2.7%); IRs in the extended data set (2-mg IR = 9.6; 4-mg IR = 14.5) were lower vs. the placebo-controlled data set (2-mg IR = 12.4; 4-mg IR = 21.3). In the All-bari AD data set, there were two positively adjudicated major adverse cardiovascular events (2-mg group): two venous thrombosis events (4-mg group) and one death. Conclusion This integrated safety analysis in patients with moderate-to-severe AD confirms the established safety profile of baricitinib.

Author(s): Thyssen, JP; de Bruin-Weller, MS; Paller, AS; Leshem, YA; Vestergaard, C; Deleuran, M; Drucker, AM; Foelster-Holst, R; Traidl-Hoffmann, C; Eyerich, K; Taieb, A; Su, JC; Bieber, T; Cork, MJ; Eichenfield, LF; Guttman-Yassky, E; Wollenberg, A | Abstract: BackgroundConjunctivitis is common in patients with atopic dermatitis (AD) in general and a commonly reported adverse event in AD clinical trials with dupilumab.ObjectiveTo survey opinions and experience about conjunctivitis occurring in AD, including those during dupilumab treatment in a group of AD experts from the International Eczema Council (IEC).MethodsElectronic survey and in-person discussion of management strategies.ResultsForty-six (53.5%) IEC members from 19 countries responded to the survey. Consensus was reached for several statements regarding diagnostic workup, referral and treatment. IEC members suggest that patients with AD should (i) routinely be asked about ocular complaints or symptoms, (ii) obtain information about the potential for conjunctivitis before starting dupilumab therapy and (iii) if indicated, be treated with dupilumab despite previous or current conjunctivitis. In cases of new-onset conjunctivitis, there was consensus that dupilumab treatment should be continued when possible, with appropriate referral to an ophthalmologist.LimitationsThe study relies on expert opinion from dermatologists. Responses from few dermatologists without dupilumab access were not excluded from the survey.ConclusionThe IEC recommends that dermatologists address conjunctivitis in patients with AD, especially during treatment with dupilumab.

BACKGROUND: Oral immunosuppressive drugs are frequently prescribed in young women with atopic dermatitis (AD). Immunocompromised patients may have a higher risk of developing high risk HPV infections, CIN and cervical carcinoma. Most literature on patients using oral immunosuppressive drugs is available in organ transplant patients. Literature on the risk of developing cervical carcinoma in AD patients treated with oral immunosuppressive drugs is lacking. At this moment there is no clear guideline/consensus on this topic, but in daily practice, questions arise concerning whether this risk is increased and whether more intensive screening in women using immunosuppressive drugs should take place.OBJECTIVE: To investigate the occurrence of cervical carcinoma in women with AD treated with oral immunosuppressive drugs.METHODS: In this retrospective cohort study in two university medical centers in the Netherlands, all female adult AD patients receiving oral immunosuppressive drugs (cyclosporine A, azathioprine, methotrexate, mycophenolate mofetil, enter-coated mycophenolic acid and extended release tacrolimus) for more than 2 months between 1989 and January 1(st) 2014 were included. Patient files in the national histopathology register were screened for PAP3a, CIN I, CIN II, CIN III and cervical carcinoma.RESULTS: A total of 257 female AD patients with one or more treatment episodes from 1989 until January 1(st) 2014 were identified and included in this study. In 189 patients (73.5%) results of cervical examination were reported in the national histopathology database. Median total duration of treatment in these 189 women was 407.0 days (IQR 243.0-940.0). No cervical carcinoma during or following immunosuppressive therapy was found in our patient group.CONCLUSIONS: No intensified screenings program for cervical neoplasia seems necessary for women with AD using oral immunosuppressive drugs. This article is protected by copyright. All rights reserved.

Background Studies assessing the relationship between disease activity and quality of life (QoL) in adults with atopic dermatitis (AD), before and after therapy are lacking. The relation between disease activity and QoL in AD patients was evaluated before (t = 0) and after 6 weeks (t = 6) of treatment with cyclosporin 5 mg/kg. Methods In 54 patients with severe AD, disease activity was assessed using objective Scoring Atopic Dermatitis index (SCORAD), Six Area Six Sign Atopic Dermatitis (SASSAD), ‘rule of nines’ extent score and serum levels of thymus and activation-regulated chemokine (TARC). Patients filled out the Dermatology Life Quality Index (DLQI). To study the relation between disease activity and QoL, correlations were calculated and regression analysis was performed. Results At t = 0 there was a small, non-significant correlation between the DLQI and the objective SCORAD, ‘rule of nines’ or serum TARC levels. At t = 6 the objective SCORAD, serum TARC and the ‘rule of nines’ score showed moderate and significant correlations with the DLQI (r = 0.34, P = 0.02; r = 0.31, P = 0.03; r = 0.49, P

Background Cyclosporin A (CsA) is being increasingly used in the treatment of severe refractory atopic dermatitis. Clinical efficacy and safety of short-term cyclosporin A treatment in atopic dermatitis patients has been proven, however, data on long-term treatment are limited. Objective The aim of this study was to investigate the efficacy, safety and the effect of discontinuation of cyclosporin A treatment in atopic dermatitis patients, with a particular focus on patients treated with cyclosporin A for more than 6 months. Methods We performed a retrospective study of clinical and adverse effects of cyclosporin A treatment in 73 atopic dermatitis patients, with an average duration of cyclosporin A treatment of 1.3 years. Results We included 73 patients (31 women and 42 men, with a mean age of 33.8 years) with severe atopic dermatitis refractory to conventional therapy that was treated with cyclosporin A. Treatment was successful in 56/73 patients. Increases in serum creatinine levels > 30% compared to baseline were reported in 7/73 patients. Arterial hypertension appeared in 11/73 patients during treatment. After discontinuation of treatment, 40/73 patients experienced a relapse and 33/73 patients experienced clinical remission for at least 3 months. No correlation between treatment duration and nephrotoxicity or hypertension was found. Strikingly, 6/73 patients experienced a rebound phenomenon. Conclusions We conclude that CsA is an effective and safe treatment for patients with severe AD refractory to conventional treatment, provided that the recommended guidelines for its administration are strictly observed. However, in contrast to previous reports, we found that 8% (6/73) of patients experienced a rebound phenomenon after discontinuation of treatment.