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20th August 2021
Allergic rhinitis is characterised by several symptoms including sneezing, itching, nasal congestion and rhinorrhoea. It can be categorised as either seasonal allergic rhinitis, in which symptoms are evoked in response to season triggers such as pollen or perennial allergic rhinitis, where symptoms are continually present. Seasonal allergic rhinitis is a global health problem and has been reported to affect 15 to 25% of adults and children. Moreover, while localised symptoms are problematic for patients, the condition also has a more generalised effect upon sufferers leading to fatigue, mood changes and reduced cognitive function which can affect work and overall quality of life. Treatment involves the use of oral and intranasal antihistamines as well as intranasal corticosteroids. However, when such treatments fail to provide symptomatic relief, subcutaneous or sublingual allergen immunotherapy can be used with subcutaneous therapy appearing to be more effective. In fact, a recent review found that the benefits of allergen immunotherapy were sustained for at least 2 – 3 years after cessation of treatment.
The role of interleukins (IL) in the pathophysiology of seasonal allergic rhinitis is uncertain although some evidence observed a trend towards higher levels of both IL-4 and IL-13. The monoclonal antibody dupilumab targets the IL-4 and IL-13 receptor and been recently shown to improve asthma and perennial allergic rhinitis symptoms. This led a team from the Department of Medicine and Paediatrics, David Geffen School of Medicine, California, US, to examine whether addition of dupilumab to subcutaneous immunotherapy would provide an additional benefit to patients with seasonal allergic rhinitis. They undertook a phase 2a, randomised trial with four arms, comparing subcutaneous immunotherapy (SCIT) either alone or combined with dupilumab verses placebo in patients with seasonal allergic rhinitis. The study involved a 12-week screening period, a 16-week treatment phase and an 8-week post-treatment follow-up in adult patients (aged 18 years and over but less than 55 years) with seasonal grass pollen allergy. The four treatment arms were: SCIT + placebo; SCIT + dupilumab 300mg every 2 weeks; Dupilumab alone; SCIT alone. The primary outcome as the percentage change from pre-baseline in the area under the curve for peak total nasal symptom score (TNSS), a composite of rhinorrhoea, nasal congestion, nasal itching, and sneezing and measured 0 – 1 hour following a nasal allergen challenge.
A total of 103 patients were enrolled and randomised to one of the four arms. The mean age of participants assigned to SCIT and dupilumab was 33 years (30.8% male) and the mean age across the study ranged from 33 to 40.3 years. At week 17 and following a nasal allergen challenge, there was no difference between SCIT and SCIT + dupilumab (least squares mean – 56.76% vs 52.03%). Similarly, there was no significant difference in the absolute change in TNSS scores. There was however, a slight, but significant improvement in the peak TNSS scores when dupilumab was added to SCIT (p = 0.026), suggesting that addition of the drug may help improve SCIT tolerability. The authors concluded that there was no benefit from adding dupilumab to SCIT in terms of reducing the response to an allergen challenge.
Corren J et al. Short-term subcutaneous allergy immunotherapy and dupilumab are well tolerated in allergic rhinitis: a randomised trial. J Asthma Allergy 2021
10th August 2021
Atopic eczema (AE) is a common, chronic, relapsing-remitting skin condition, characterised by inflammation and intense pruritus and which has a substantial impact on quality of life. It affects up to 22.6% of children, whereas the prevalence in adults varies between 1.2 to 17.1%. While the precise cause of AE remains to be clarified, it is driven by pro-inflammatory interleukins (IL) including IL-4 and IL-13. Evidence that these two cytokines have an important role in the pathophysiology comes from studies with the monoclonal antibody, dupilumab. Though dupilumab was the first biologic agent to be used in patients with moderate-to-severe atopic eczema, only just over a third of patients in two of the largest trials achieved the primary endpoint of clear or almost clear skin. Thus, other pathways are likely to be involved in AE and recent work has implicated the Janus Kinase pathway (JAK) in the signalling of several interleukins including IL-4 and IL-13. Upadacitinib is an oral JAK inhibitor which is currently licensed for use in rheumatoid arthritis. Nevertheless, a recent phase 3 trial in patients with moderate-to-severe AE found that when combined with topical steroids, oral upadacitinib at a dose of either 15 or 30 mg, led to a significant improvement in disease severity in over 60% of patients. While such data highlights that upadacitinib is an effective treatment, what is less clear, is its position in the eczema treatment pathway. This led a team from Oregon Medical Research Centre, Portland, US, to undertake a randomised trial, comparing upadacitinib with dupilumab. Eligible patients were adults aged 18 to 75 years, diagnosed with AE and who were candidates for systemic treatment, after a failure of topical therapy. All were randomised 1:1 to 30mg of upadacitinib given once daily until week 24 or 300mg dupilumab subcutaneously every 2 weeks (after a 600mg loading dose). The primary outcome was an EASI75, which represents a 75% improvement in disease severity at week 16.
A total of 348 participants with a mean age of 36.6 years (52.6% male) were randomised to upadacitinib and 344 with the same mean age (56.4% male) to dupilumab. After 16 weeks, 71% using upadacitinib and 61.1% given dupilumab achieved an EASI75 (p = 0.006). In addition, 27.9% using upadacitinib and 7.6% using dupilumab, achieved an EASI100 (p < 0.001), i.e., were completely clear of their eczema. There were also significantly better improvements in measure of itch severity using upadacitinib compared to dupilumab.
Based on these findings, the authors concluded that upadacitinib was well tolerated and provided superior efficacy to dupilumab.
Blauvelt A et al. Efficacy and Safety of Upadacitinib vs Dupilumab in Adults with Moderate-to-Severe Atopic Dermatitis. A Randomised Clinical Trial. JAMA Dermatol 2021