Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo‐controlled,randomized phase III clinical trial (LIBERTY AD CAFÉ)

Atopic dermatitis (also called AD or eczema) is a chronic skin disease found in up to 1 in 10 adults, causing itchy rashes that may cover most of the body. Ciclosporin, an oral treatment (taken by mouth) commonly used for AD, doesn't always work and can have significant side effects. Other broadly‐acting oral medications are sometimes used, but not approved, for AD. Dupilumab is a new medication approved in many countries for adults with inadequately controlled moderate‐to‐severe AD. Dupilumab specifically targets pathways in the body that drive AD. Researchers in Europe evaluated how well dupilumab injections improved rashes, itch, and daily lives of people whose AD required ciclosporin, but for whom ciclosporin wasn't working or caused intolerable side effects, or whose medical conditions prevented its use. Among 325 participants, 110 received 300 mg dupilumab once‐weekly, 107 received it every two weeks, and 108 received placebo (dummy drug) once‐weekly. All participants used topical (applied to the skin) corticosteroids during the 16‐week study. Dupilumab improved AD rashes: at Week 0, participants’ Eczema Area and Severity Index (EASI) scores were about 31 (scale: 0–72), but by Week 16, 59% to 62% of dupilumab‐treated participants achieved 75% or greater improvement in EASI, versus 29.6% of people on placebo. Dupilumab also improved itch, other symptoms, mood, and quality of life. Conjunctivitis and injection‐site reactions were more frequent among dupilumab‐treated patients; skin infections (excluding herpes) and AD exacerbations (worsening) were more frequent with placebo. The authors conclude that dupilumab plus topical corticosteroids significantly improved AD even in adults with AD who had previously failed treatment with or were unable to use ciclosporin.     

Dupilumab treatment improves quality of life in adult patients with moderate‐to‐severe atopic dermatitis: results from a randomized,placebo‐controlled clinical trial

Atopic dermatitis is a skin disease, commonly known as eczema. It affects up to 1 in 10 adults. Atopic dermatitis is usually very itchy, causing people to wake up at night, and feel “low”. This state of general discomfort is known as reduced quality of life. Dupilumab is a new treatment approved in the U.S.A. for adults with moderate‐to‐severe atopic dermatitis. The treatment blocks some of the mechanisms involved in the disease. In a clinical trial conducted in Europe, researchers observed 109 patients with moderate‐to‐severe atopic dermatitis. The patients received dupilumab over 12 weeks. They found that the treatment improved the eczema and its symptoms, such as itch. The researchers also studied how the treatment affected quality of life in 64 out of 109 patients in the study. These patients had answered a set of questions that measures how atopic dermatitis affects their quality of life (Quality of Life Index for atopic dermatitis [QoLIAD]). Thirty‐two patients received dupilumab 300 mg weekly, by injection under the skin, and 32 received placebo. About 6 out of 10 patients treated with dupilumab had better quality of life over the 12 weeks, whereas only about 1 in 10 placebo‐treated patients improved. The researchers also found a relatively strong link between improvements with dupilumab in QoLIAD score and improvements in the eczema and symptoms. Dupilumab was well‐tolerated by the patients. The authors conclude that dupilumab, a new breakthrough treatment for atopic dermatitis, improves eczema and its symptoms, and in turn, the patients’ quality of life.     

Fifty‐two week follow‐up safety and effectiveness results of dupilumab treatment of moderate‐to‐severe atopic dermatitis from a retrospective,multicentric series

Atopic dermatitis (AD) is a chronic, systemic disease that has a multifactorial etiology, where immune system disorders and epidermal barrier dysfunction are added to the influence of genetic and environmental factors. Dupilumab has been approved by United States and the European Union regulatory agencies in 2017 for the treatment of moderate‐to‐severe AD in adult patients who are candidates for systemic treatment. In this short report, we present a retrospective, multicentric study, in which five hospitals in Andalusia, Spain, have taken part. Our objective is to evaluate the safety and effectiveness of dupilumab in patients with moderate‐to‐severe AD treated with dupilumab with at least 52 weeks of follow‐up.     

Infections in Dupilumab Clinical Trials in Atopic Dermatitis: A Comprehensive Pooled Analysis

Background

Patients with moderate-to-severe atopic dermatitis (AD) have increased infection risk, including skin infections and systemic infections. Immunomodulators (e.g., anti-tumor necrosis factors, anti-interleukin [anti-IL]-23, anti-IL-17, Janus kinase inhibitors) increase risk of infections. Dupilumab (a monoclonal antibody blocking the shared receptor component for IL-4 and IL-13) is approved for inadequately controlled moderate-to-severe AD and for moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma.

Objective

The aim was to determine the impact of dupilumab on infection rates in patients with moderate-to-severe AD.

Methods

This analysis pooled data from seven randomized, placebo-controlled dupilumab trials in adults with moderate-to-severe AD. Exposure-adjusted analyses assessed infection rates.

Results

Of 2932 patients, 1091 received placebo, 1095 dupilumab 300 mg weekly, and 746 dupilumab 300 mg every 2 weeks. Treatment groups had similar infection rates overall per 100 patient-years (placebo, 155; dupilumab weekly, 150; dupilumab every 2 weeks, 156; dupilumab combined, 152), and similar non-skin infection rates. Serious/severe infections were reduced with dupilumab (risk ratio 0.43; p < 0.05), as were bacterial and other non-herpetic skin infections (risk ratio 0.44; p < 0.001). Although herpesviral infection rates overall were slightly higher with dupilumab than placebo, clinically important herpesviral infections (eczema herpeticum, herpes zoster) were less common with dupilumab (risk ratio 0.31; p < 0.01). Systemic anti-infective medication use was lower with dupilumab.

Conclusions

Dupilumab is associated with reduced risk of serious/severe infections and non-herpetic skin infections and does not increase overall infection rates versus placebo in patients with moderate-to-severe AD.

ClinicalTrials.gov Identifiers

NCT01548404, NCT02210780, NCT01859988, NCT02277743, NCT02277769, NCT02260986, and NCT02755649.

     

Effectiveness and safety of a prevention‐of‐flare‐progression strategy with pimecrolimus cream 1% in the management of paediatric atopic dermatitis

Objective This study was performed to investigate the efficacy and safety of a prevention‐of‐flare‐progression strategy with pimecrolimus cream 1% in children and adolescents with atopic dermatitis (AD). Methods A 26‐week multi‐centre, randomized, double‐blind, vehicle‐controlled study was conducted in 521 patients aged 2–17 years, with a history of mild or moderate AD, who were clear/almost clear of disease before randomization to pimecrolimus cream 1% (n = 256) or vehicle cream (n = 265). Twice‐daily treatment with study medication was started at the first signs and/or symptoms of recurring AD. If, despite the application of study medication for at least 3 days, AD worsened (as confirmed by the investigator), treatment with a moderately potent topical corticosteroid (TCS) was allowed in both groups. The primary efficacy end point was the number of days on study without TCS use for a flare. Results The mean number of TCS‐free days was significantly higher (P < 0.0001) in the pimecrolimus cream 1% group (160.2 days) than in the control group (137.7 days). On average, patients on pimecrolimus cream 1% experienced 50% fewer flares requiring TCSs (0.84) than patients on vehicle cream (1.68) (P < 0.0001). Patients on pimecrolimus cream 1% also had fewer unscheduled visits (87) than patients on vehicle cream (246). Conclusions In children and adolescents with a history of mild or moderate AD but free/almost free of signs or symptoms of the disease, early treatment of subsequent AD exacerbations with pimecrolimus cream 1% prevented progression to flares requiring TCS, leading to fewer unscheduled visits and reducing corticosteroid exposure.     

Subcutaneous methotrexate in patients with moderate‐to‐severe psoriasis: a critical appraisal

This article is a review of a study, published in the Lancet, by R.Warren and colleagues, based in the U.K. and western Europe. The authors compared 17.5mg weekly methotrexate, given by subcutaneous injection, with placebo in 120 patients with moderate to severe psoriasis who had not previously received the drug. The first sixteen weeks of the study were a randomised controlled trial, meaning patients were randomly selected to either receive the drug or a placebo; patients continued an open study on methotrexate for up to a year. The dose was increased to 22.5 mg weekly if they did not improve on the lower dose to achieve PASI 50 at week 24. PASI is used to record the redness, thickness and scaling of a patient's psoriasis and to measure how well a treatment works, as a reduction in the PASI score means a reduction in these symptoms; for example PASI 75 means the patient has a 75% or more reduction in their PASI score from the start. The authors took blood tests and skin biopsies from patients on methotrexate and found changes on microscopic examination, including a decrease in CD3 positive lymphocytes and cytokine markers, and this implies that the drug works by its effect on the immune system. Blood tests showed no significant abnormality. At week 16, 41% of patients on methotrexate achieved PASI 75 improvement, compared to 10% of patients on placebo. The reviewers observed that, although methotrexate is widely used as a systemic treatment for psoriasis, there have been no previous randomised placebo controlled trials. This trial is therefore welcome, although only the first phase is placebo controlled. Traditionally, patients are given a small test dose (e.g. 5 or 7.5mg), and the dose is increased gradually over successive weeks. The investigators encountered no adverse events from starting on a higher dose. The reviewers noted that methotrexate by injection was not compared with the oral form of the drug (taken by mouth), which might be equally effective and is substantially cheaper. The unusually high response to placebo may be due in part to alcohol avoidance, which is advised for patients on methotrexate. The changes on skin biopsy are of interest, but it was not possible to correlate them with clinical response to the drug.     

Management of dupilumab‐associated conjunctivitis in atopic dermatitis

Since September 2017, the monoclonal antibody dupilumab (Dupixent^®) has been approved in the EU for the treatment of moderate‐to‐severe atopic dermatitis. By blocking IL‐4 and IL‐13 signaling pathways, dupilumab improves both objective signs and subjective symptoms of the disease. Blocking of the IL‐4aRα subunit leads to improvement of the skin's barrier function and reduction in Th2‐mediated inflammation. While the rate of adverse events on dupilumab is generally low, mild‐to‐moderate conjunctivitis associated with redness as well as a burning and foreign body sensation has been reported in up to 28 % of patients. Treatment options include topical corticosteroids and topical calcineurin inhibitors. The present review highlights the clinical presentation of dupilumab‐associated conjunctivitis and addresses pharmacological and non‐pharmacological options available for the treatment of this clinically highly relevant condition.     

Low‐dose methotrexate treatment for moderate‐to‐severe atopic dermatitis in adults

Background Atopic dermatitis (AD) is a common inflammatory skin disease. Methotrexate (MTX) was suggested as an effective treatment option in cases of moderate‐to‐severe atopic dermatitis. This study assessed the efficacy and safety of treatment with low weekly doses of methotrexate for moderate‐to‐severe AD in adults. Methods Twenty adult patients with moderate‐to‐severe AD were included in this retrospective study. Those patients were unresponsive to topical treatments, antihistamines and at least one of the second‐line treatments. MTX in low weekly doses of 10–25 mg was administered orally or intramuscularly with folic acid supplementation 5 mg per week for at least 8–12 weeks. The response to treatment was evaluated by change in SCORAD (SCORing Atopic Dermatitis), DLQI (Dermatology Quality of Life Index) and the global assessment of the clinical response score. Results After 8–12 weeks of treatment, we observed an objective response in most patients. There were 16 responders and 4 non‐responders. The mean SCORAD and DLQI decreased by 28.65 units (44.3%) and 10.15 units (43.5%), respectively. The first improvement was observed after a period ranging from 2 weeks to 3 months (mean 9.95 w ± 3.17). Treatment was more effective in adult onset AD than in childhood onset. Tolerance of treatment was good. However, nausea and an increase of liver enzymes were observed in 5 patients and 3 of them required a transient discontinuation of MTX. One patient developed peripheral neuropathy, which was resolved several weeks after the discontinuation of MTX. Conclusion MTX seems to be an effective and safe second‐line treatment for patients with moderate‐to‐severe atopic dermatitis. A randomized, controlled study is warranted.     

The use of selective Th2 blocker dupilumab for the treatment of atopic dermatitis in a heart transplant patient: Case report

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by relapsing eczematous rash with severe pruritus and recurrent infection. Topical emollients and immune‐modulators (e.g., corticosteroids and calcineurin inhibitor) are first‐line therapies for acute flares. In severe refractory cases, systemic immunosuppression may be required. Increased incidence of AD has been documented in heart‐transplant children who receive their transplant or thymectomy before the age of 1 year. The treatment of these patients remains a conundrum for dermatologists. We present a case report of a chronically immunosuppressed transplant patient with severe AD treated with dupilumab and in remission for over 2 years with minimal side effects. We will also discuss impact of transplant immunosuppression in the pathogenesis of AD.     

Toll‐like receptor 4 attenuates a murine model of atopic dermatitis through inhibition of langerin‐positive DCs migration

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that is often associated with skin barrier dysfunction leading to a higher frequency of bacterial and viral skin infections. Toll‐like receptor (TLR) 4 on resident skin cells was involved in sensing pathogens and eliciting pathogen‐specific innate and adaptive immune responses. Previous studies have demonstrated that TLR4 was linked to AD severity in context of pathogen infection. However, the immune regulatory role of TLR4 in AD remains to be defined. We here investigated the immune regulatory function of TLR4 in AD induced by repeated epicutaneous application of a hapten, 2,4‐dinitrochlorobenzene (DNCB). Our results showed that TLR4‐deficient (TLR4^?/?) mice exhibited more severe AD symptoms than WT mice after DNCB challenge. The DNCB‐treated TLR4^?/? mice also displayed higher expression levels of inflammatory cytokines and stronger Th2 response than WT counterparts. Moreover, the skin expression of thymic stromal lymphopoietin (TSLP), an important potential contributor to allergic inflammation, was significantly elevated in TLR4^?/? mice compared with that in WT mice upon DNCB administration. Furthermore, we demonstrated that the migration of langerin‐positive dendritic cells (DCs) into draining lymph nodes was enhanced in TLR4^?/? mice following DNCB challenge, which is partially dependent on the production of pro‐inflammatory cytokine TNF‐α. Together, these results determined that TLR4 affected the hapten‐induced skin inflammation in the absence of exogenous pathogen infection, suggesting that TLR4 not only regulates infection but also may serve as a modulator of the immune response during AD development.     

Twice‐weekly treatment with tacrolimus 0.03% ointment in children with atopic dermatitis: clinical efficacy and economic impact over 12 months

Background Rational healthcare decision‐making based on clinical and economic evidence is essential to provide the best possible care for patients with atopic dermatitis (AD). Objective To evaluate treatment outcomes, resource use and cost associated with twice‐weekly tacrolimus 0.03% ointment treatment vs. standard flare‐only therapy in children with moderate‐to‐severe AD. Methods In a pan‐European, Phase III multicentre randomized clinical trial, children with mild‐to‐severe AD were randomized to 0.03% tacrolimus ointment or vehicle twice weekly for 12 months. Disease flares were treated using open‐label tacrolimus 0.03% ointment twice daily. Clinical efficacy data were evaluated in a subgroup of 153 children with moderate‐to‐severe AD, with resource use data – collected prospectively using caregiver questionnaires – available from 146 children. Pooled costs of resource use were determined using German unit cost data. Direct and indirect costs were considered from third‐party payer, patient and caregiver, and societal perspectives. Results Twice‐weekly tacrolimus ointment reduced the number of flares compared with standard therapy (P < 0.001) and prolonged time to first flare (146 vs. 17 days, P < 0.001). Mean ± SD annual costs per patient for standard and twice‐weekly therapy respectively were €2002 ± 2315 vs. €1571 ± 1122 for severe AD and €1136 ± 1494 vs. €1233 ± 1507 for moderate AD. Conclusions In children with AD, twice‐weekly treatment with tacrolimus 0.03% ointment reduces the number of flares and prolongs time spent free from flares with no additional cost in children with moderate AD, and may be cost‐saving in those with severe AD.     

Treatment of primary perniosis with oral pentoxifylline (a double‐blind placebo‐controlled randomized therapeutic trial)

Primary perniosis is an annoying cold‐induced dermatosis. Many therapeutic agents have been tried with either unsatisfactory or controversial results. The aim of this study was to assess the efficacy of oral pentoxyfylline in the treatment of primary perniosis. A double‐blind placebo‐controlled randomized therapeutic study conducted in dermatology department of Al‐Yarmouk Teaching Hospital, Baghdad, Iraq during four winter seasons between 2010 and 2014. The patients were randomly allocated into two equal groups: group A patients were given oral pentoxyfylline 400 mg thrice daily whereas patients in group B were given an identical placebo tablet thrice daily for 3 weeks. Therapeutic response of both groups was clinically assessed weekly for 3 weeks and side‐effects were recorded. A total of 110 patients with chilblains completed this therapeutic trial. The mean age was 24.98 ± 9.17 year. Male to female ratio was 1:2.4. All patients presented with erythematous papules, plaques or nodules. Very good therapeutic response was significantly better for group A than that of group B at 7th, 4th, and 21st days of the trial (p‐value: 0.0148, 0.0000004, and 0.0000000, respectively). No side effects were encountered in both groups. Pentoxyfylline is an effective and safe drug for treatment of primary perniosis.     

Assessing the need for routine safety testing for patients being treated with dupilumab for moderate-to-severe atopic dermatitis

Atopic dermatitis (also known as AD or eczema) is a common skin disease that can cause intense and persistent itching and rashes. Skin creams or ointments are not suitable or effective for some patients with moderate-to-severe AD. In these patients, oral (taken by mouth) or injected medications may be required. Some of those oral or injected treatments could be toxic and often have unwanted side effects, especially when used for a longer period of time, so patients must be regularly tested to see whether those treatments are harming their blood or organs. Dupilumab is a newer injectable drug for treating moderate-to-severe AD. Dupilumab specifically targets key molecules in the body that cause AD. Dupilumab has been tested for up to one year in more than 2000 patients enroled in placebo-controlled clinical trials. During those trials, patients provided blood and urine samples for laboratory testing while they were being treated with dupilumab or placebo (dummy drug). In this paper, the authors from Germany and the U.S.A, analysed how blood cells, blood chemistry, and urine chemistry changed during treatment, to check whether dupilumab is safe to use without the need for regular laboratory tests. After performing many routine laboratory tests on patients’ blood and urine, they found that there were no clinically important changes in test results that could be linked to dupilumab. They concluded that patients using dupilumab for moderate-to-severe AD do not need routine laboratory testing. This is a summary of the study: Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS)     

Higher baseline serum lactate dehydrogenase level is associated with poor effectiveness of dupilumab in the long term in patients with atopic dermatitis

Dupilumab shows high efficacy and tolerable safety for the treatment of atopic dermatitis (AD). However, the extent of its effectiveness varies in individual patients. To date, practical predictors of later effectiveness of dupilumab in AD patients have not been reported. To explore practical predictors of later effectiveness of dupilumab in AD, we retrospectively investigated the correlation of baseline demographics and baseline laboratory results with the percentage reduction in Eczema Area and Severity Index (EASI) scores at 1, 3, 6 and 12 months after initiating dupilumab. Furthermore, multiple regression analyses were conducted. Data were collected from patients’ charts. Data on 54 Japanese adult patients (43 men and 11 women) with moderate to severe AD were analyzed. Baseline serum lactate dehydrogenase (LDH) level was negatively correlated with the percentage reduction in EASI score at 3, 6 and 12 months after initiating dupilumab but not at 1 month. Multiple regression analyses also revealed that effectiveness of dupilumab at 3 and 6 months was associated with lower baseline serum LDH level. AD patients with allergic diseases tended to have lower percentage reduction in EASI at 1 month, but had higher percentage reduction in EASI in the long term than patients without allergic diseases. In conclusion, higher baseline serum LDH level was associated with poor effectiveness of dupilumab in the long term in patients with AD. Furthermore, it tended to take a longer time for AD patients with allergic diseases to respond to dupilumab, and these patients responded better to dupilumab in the long term than patients without allergic diseases.     

Efficacy and tolerability of biologic and nonbiologic systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials

Background The comparative efficacy and tolerability of conventional and biologic treatments for moderate‐to‐severe plaque psoriasis are unknown. Objectives To perform a systematic review and meta‐analysis of randomized controlled trials (RCTs) reporting efficacy of systemic treatments approved for moderate‐to‐severe psoriasis by means of the Psoriasis Area and Severity Index (PASI). Methods We identified relevant articles by systematic electronic searches (Cochrane Library, Medline, Embase, Scopus). Efficacy was defined as proportion of participants with ≥ 75% decrease in PASI (PASI‐75) at primary efficacy measurement (week 8–16). PASI‐75 response rates of double‐blind placebo‐controlled trials were summarized as risk differences (RDs) and pooled using random effects models. Tolerability was assessed from rates of withdrawals and adverse events. Results Twenty‐four RCTs totalling 9384 patients were analysed qualitatively. Sixteen double‐blind placebo‐controlled trials were eligible for meta‐analysis. Infliximab was significantly superior to all other interventions [RD 77%, 95% confidence interval (CI) 72–81%]. Adalimumab (RD 64%, 95% CI 61–68%) was superior to ciclosporin (RD 33%, 95% CI 13–52%), efalizumab (RD 24%, 95% CI 19–30%), etanercept 50 mg twice weekly (RD 44%, 95% CI 40–48%) and etanercept 25 mg twice weekly (RD 30%, 95% CI 25–35%). Efalizumab was significantly less efficacious than fumaric acid esters (RD 48%, 95% CI 32–64%). Rates of withdrawals due to adverse events were highest for methotrexate and fumaric acid esters. Conclusions The efficacy of systemic agents approved for moderate‐to‐severe psoriasis differs considerably both within and between biologics and nonbiologics. Infliximab is most efficacious, followed by adalimumab. Patients receiving infliximab have an excess chance of 77% over placebo to achieve PASI‐75 response. Published evidence questions regulatory guidelines that recommend biologics as second‐line therapy for moderate‐to‐severe plaque psoriasis.     

Combination of glucosamine and low‐dose cyclosporine for atopic dermatitis treatment: A randomized,placebo‐controlled,double‐blind,parallel clinical trial

Our recent pilot study showed better outcomes using a combination of low‐dose cyclosporine and glucosamine than cyclosporine alone in the treatment of atopic dermatitis (AD). Here, a randomized, placebo‐controlled, double‐blind, parallel‐designed study was planned to compare the efficacy and safety of low‐dose cyclosporine and glucosamine combination to low‐dose cyclosporine alone for the treatment of patients with moderate to severe AD. AD patients with a Severity Scoring of Atopic Dermatitis (SCORAD) index ≥30 were randomly assigned in a 1:1 ratio to receive either cyclosporine 2 mg/kg and glucosamine 25 mg/kg (group A) or cyclosporine and placebo (group B) for 8 weeks. SCORAD indices, serum levels of chemokine ligand 17 and interleukin‐31, eosinophil counts, and blood cyclosporine levels were examined before and after treatment. The SCORAD indices for group A (n = 19) were significantly reduced after the treatment and a significant correlation between the changes in the SCORAD indices and changes in the serum levels of chemokine ligand 17, but not interleukin‐31, was detected. Glucosamine combined with cyclosporine did not increase adverse events and serum cyclosporine levels compared with cyclosporine alone. Therefore, combination of low‐dose cyclosporine and glucosamine may be useful to allow the long‐term use of cyclosporine in the treatment of patients with moderate to severe AD.     

An Innovative Oat‐Based Sterile Emollient Cream in the Maintenance Therapy of Childhood Atopic Dermatitis

Although emollients are recommended in the management of atopic dermatitis (AD), regimens for emollient maintenance therapy are awaiting validation. We conducted an international, multicenter, open‐label trial to assess the effects of a 3‐month maintenance treatment regimen with a sterile, preservative‐free emollient cream containing oat plantlets in children (ages 6 mos–6 yrs) with moderate AD. After a 14‐day run‐in stabilization phase using a topical corticosteroid (TCS) treatment of medium potency, 108 children with a SCORing Atopic Dermatitis (SCORAD) index of 20 or less were included in the study. Emollient was applied twice daily for 3 months. Rescue TCS treatment was used only in cases of flare‐ups. The SCORAD index, Patient‐Oriented SCORAD (PO‐SCORAD) index, number of flares, TCS use, and tolerance were assessed at months 1, 2, and 3 (M1, M2, M3). AD severity improved, with a highly significant decrease in the SCORAD and PO‐SCORAD indexes at M2 and M3 (p < 0.001). Changes from baseline to M3 were 48.6 ± 73.6% for SCORAD and 29.6 ± 125.3% for PO‐SCORAD. The number of flares and TCS use significantly decreased by M3 (both p < 0.001). Very good tolerance was recorded in 100% of children at M2 and M3. Notwithstanding the limitations inherent in open‐label trials, twice daily application of the oat‐based sterile emollient cream led to a significant improvement of clinical symptoms, evidenced by parallel changes in the SCORAD and PO‐SCORAD indexes and fewer flare‐ups. Clinical benefit and less TCS use were maintained at M3. Tolerance was very good.     

Efficacy and safety of tofacitinib for moderate‐to‐severe plaque psoriasis: a systematic review and meta‐analysis of randomized controlled trials

The effects of tofacitinib in treating moderate‐to‐severe plaque psoriasis were unclear. We aimed to assess the effects of tofacitinib in treating moderate‐to‐severe plaque psoriasis. We searched PubMed, Cochrane Central Register of Controlled Trials and EMBASE for relevant randomized controlled trials (RCTs) and conducted a systematic review and meta‐analysis. Four RCTs with 2724 participants were included. Compared to placebo, tofacitinib significantly improved psoriasis {≥75% reduction in the Psoriasis Area and Severity Index score: 5 mg BID: risk difference (RD) 0.32 [95% confidence interval (CI) 0.28–0.35], 10 mg BID: RD 0.51 (95% CI 0.43–0.58); ≥90% reduction in the Psoriasis Area and Severity Index score: 5 mg BID: RD 0.19 (95% CI 0.17–0.22), 10 mg BID: RD 0.36 (95% CI 0.31–0.42); Physician's Global Assessment 0/1: 5 mg BID: RD 0.31 (95% CI 0.27–0.35), 10 mg BID: RD 0.48 (95% CI 0.44–0.53)} and participants’ life quality [Dermatology Life Quality Index 0/1: 5 mg BID: RD 0.24 (95% CI 0.20–0.2), 10 mg BID: RD 0.36 (95% CI 0.33–0.40)]. Tofacitinib was associated with an increase in minor adverse events [upper respiratory tract infection: 5 mg BID: RD 0.02 (95% CI 0.00–0.03), 10 mg BID: RD 0.02 (95% CI 0.00–0.04); hypercholesterolaemia: 5 mg BID: RD 0.02 (95% CI 0.01–0.04), 10 mg BID: RD 0.02 (95% CI 0.01–0.04)]. In conclusion, tofacitinib may be a treatment option for moderate‐to‐severe plaque psoriasis that is unresponsive to other therapies and patients who are intolerable to other therapies or prefer oral medications.