Summary Background Dupilumab blocks the shared receptor component for interleukin (IL)‐4 and IL‐13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate‐to‐severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate‐to‐severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate‐to‐severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo. Objectives To characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials. Methods We evaluated randomized placebo‐controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47). Results In most AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators. In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase the incidence compared with placebo. In the EoE trial, no patients had conjunctivitis. Conclusions Conjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the incidence of conjunctivitis was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab‐treated patients require further study. What's already known about this topic? Ocular disorders, including allergic conjunctivitis, are common in patients with atopic dermatitis (AD). In most dupilumab AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than those receiving placebo. Most cases were mild to moderate and recovered or were recovering during study treatment; study treatment discontinuation due to conjunctivitis was rare. Conjunctivitis incidence was very low and similar for dupilumab and placebo in clinical trials in asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis. What does this study add? This analysis confirms and extends the results of the individual clinical trials. Baseline disease‐related factors, including AD severity, prior conjunctivitis history and certa...

Human immunodeficiency virus (HIV) replication is linked to cellular gene transcription and requires target cell activation. The latent reservoir of HIV-1 in quiescent T cells is thought to be a major obstacle to clearance of infection by highly active antiretroviral therapy (HAART). Thus, identification of agents that can induce expression of latent virus may, in the presence of HAART, allow elimination of the infected cells by the immune response. We previously used the SCID-hu (Thy/Liv) mouse model to establish that activation-inducible HIV can be generated at high frequency during thymopoiesis. Latently infected mature thymocytes can be exported into the periphery, providing an efficient primary cell model to determine cellular activation signals that induce renewed expression of latent virus. Here we characterized the effects of prostratin, a non-tumor-promoting phorbol ester, on primary human peripheral blood lymphocytes (PBLs) and assessed its ability to reactivate latent HIV infection from thymocytes and PBLs in the SCID-hu (Thy/Liv) model. Prostratin stimulation alone did not induce proliferation of quiescent PBLs; however, it could provide a secondary signal in the context of T-cell receptor stimulation or a primary activation signal in the presence of CD28 stimulation to induce T-cell proliferation. While prostratin alone was not sufficient to allow de novo HIV infection, it efficiently reactivated HIV expression from latently infected cells generated in the SCID-hu mouse. Our data indicate that prostratin alone is able to specifically reactivate latent virus in the absence of cellular proliferation, making it an attractive candidate for further study as an adjunctive therapy for the elimination of the latent HIV reservoir.

Summary Conjunctivitis is a common condition that causes the eye to become red, itchy and oozing. It is common in patients with atopic dermatitis (also called eczema), and in other allergic diseases, including asthma. Apart from allergies, conjunctivitis can also be caused by infections, chemicals, irritants, and other diseases. Dupilumab is a prescription medicine approved in the USA for people 12 years and older with moderate‐to‐severe AD uncontrolled by topical (applied to the skin) prescription medicines or who cannot use topical medicines, for adults in other countries whose AD is uncontrolled with existing therapies, and for people 12 years and older for maintenance treatment of moderate‐to‐severe asthma uncontrolled with their current medicines. Dupilumab blocks activity of specific substances that cause these allergic diseases. In most AD studies, more dupilumab‐treated patients had conjunctivitis than patients on placebo (dummy drug). To investigate this effect, the authors assessed rates, risk factors, severity, and outcomes of conjunctivitis in 11 dupilumab studies in AD, asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and eosinophilic esophagitis (EoE). In 5 of 6 AD studies, dupilumab‐treated patients were more likely to get conjunctivitis than placebo‐treated patients. No conjunctivitis was confirmed to be caused by infection, and it does not seem to be allergic in nature. Patients who entered these studies with more severe AD or who previously had conjunctivitis were more likely to get conjunctivitis. In asthma and CRSwNP studies, conjunctivitis rates were less frequent for both dupilumab and placebo than in AD studies, and were similar for dupilumab and placebo. In the EoE study, nobody had conjunctivitis. In all studies, conjunctivitis was mostly mild to moderate; most cases recovered during the treatment period. Causes of conjunctivitis in dupilumab‐treated patients require further study.

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Background: Citalopram is a racemic selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of depression. Citalopram is a racemate and its serotonin reuptake inhibitory activity resides primarily in the single S-isomer, escitalopram, which is now being evaluated for its potential usefulness in the treatment of depression and other psychiatric disorders. Results from placebo-controlled studies that also included Citalopram as an active control have shown that escitalopram is effective in treating depression and associated symptoms of anxiety. However, none of these studies was powered sufficiently to detect differences between active treatment groups. The goal of the present analysis is to evaluate the efficacy of escitalopram compared with Citalopram in the treatment of major depressive disorder.Method: Data were pooled from three similarly designed, randomized, double-blind, placebo-controlled trials of escitalopram (10–20 mg/day) and Citalopram (20–40 mg/day). Patients were male or female, ≥18 years of age, who met criteria for a major depressive episode with a Montgomery Asberg Depression Rating Scale (MADRS) score ≥22 at baseline. Efficacy measures included change from baseline in MADRS score and the Clinical Global Impression of Improvement (CGI-I) scale. Improvement in associated symptoms of anxiety was measured using the change from baseline in the MADRS inner tension item.Results: Both escitalopram and Citalopram significantly improved depression and anxiety symptoms compared with placebo, and there were significantly more MADRS responders (defined as ≥50% improvement in MADRS scores at end point) in the escitalopram and Citalopram treatment groups. Escitalopram treatment was associated with statistically significant improvements in all efficacy measures relative to placebo after 1 week of treatment, whereas Citalopram treatment statistically separated from placebo at the end of week 4 (CGI-I and MADRS inner tension) or week 6 (MADRS). Escitalopram treatment also was statistically significantly superior to Citalopram treatment at a number of time points.Conclusion: These data support the effectiveness of escitalopram and Citalopram in the treatment of major depressive disorder, and suggest escitalopram may have a faster onset and greater overall magnitude of effect than citalopram in improving symptoms of depression and anxiety in patients with major depressive disorder.