SCIENCE

November 2019

Sign up for receiving the updates by email here


Efficancy and safety of dupilumab (D) in patients with severe chronic sinusitis with nasal polyps (CRSwNP)
C. Bachert et al: The Lancet September 2019 "first online"

Already in 2016, (JAMA Feb) Cl. Bachert and his team had mentioned the efficacy of D. human monoclonal antibody that inhibits signalling of interleukin (IL)-4 and IL-13, in a small group of CRSwNP which often needs systemic corticosteroid use and repeated sinus surgery. They decided to extend this treatment to 2 cohorts coming from many countries: Liberty Sinus 24 and Liberty-Sinus 52 in adults.
SINUS-24 was done in 67 centres in 13 countries, and SINUS-52 was done in 117 centres in 14 countries.
Patients in SINUS-24 were randomly assigned to subcutaneous D 300 mg or placebo every 2 weeks for 24 weeks. Patients in SINUS-52 were randomly assigned to D 300 mg every 2 weeks for 52 weeks, D every 2 weeks for 24 weeks and then every 4 weeks for the remaining 28 weeks. All patients were randomly assigned centrally with a permuted block randomization schedule. Coprimary endpoints were changes from baseline to week 24 in nasal polyp score (NPS). Safety was assessed in a pooled population of both D groups. Results : D significantly improved the coprimary endpoints in both studies. It reduced polyp size, sinus opacification, and severity of symptoms and was well tolerated. The most common adverse events were more frequent with placebo.
In conclusion: Adding D to daily standard of care for patients with severe CRSwNP is a therapeutic option which deserves consideration.

 

 

Oral immunotherapy (OIT) in patients with peanut allergy: New data
Chinthraja S et al. The lancet 12 Sept 19 "first online"

The researchers of Stanford University USA undertook a randomized, phase 2 study, on long term outcomes with sequential and immunological testing in patients with peanut allergy aged 7–55 years with a positive and food challenge (DBPCFC ≤500 mg of peanut protein. Via a computerized system, 3 groups were build up:
- The first one was maintained on 4000 mg peanut protein through to week 104 then discontinued (peanut-0 group),
- The other group ingest 300 mg peanut protein daily (peanut-300 group) for 52 weeks,
- The third receive oat flour (placebo group).
DBPCFCs to 4000 mg peanut protein were done at baseline and weeks 104, 117, 130, 143, and 156.
The primary efficacy and safety analysis was done on 120 participants, randomly assigned to the peanut-0 (n=60), peanut-300 (n=35), and placebo groups (n=25). Over the entire study, the most common adverse events were mild gastrointestinal symptoms, which were seen in 90 of 120 patients and decreased over time in all groups.
In the peanut-0 group, eight (13%) of 60 participants passed DBPCFCs at week 156, had higher baseline peanuts specific IgG4 to IgE ratio and lower Ara h 2 IgE basophil activation responses, all criteria associated with sustained unresponsiveness, symptom of desensitization.
This peanut OIT is an alternative strict avoidance of allergen or to other dangerous immunotherapy. It could desensitize allergic patients to 4000mg peanut protein but discontinuation or reduction to 300mg daily increase the likelihood of regaining clinical reactivity to peanut. This information for clinicians is helpful for an optimal management.

 

 

Chronic spontaneous urticaria (CSU): A new biotherapy ligelizumab (L)
Maurer M. et al. NEJM October 2019 381 1321-32

L is a next generation high-affinity humanized monoclonal anti-IgE antibody which acts in removing IgE from Fc € receptor on mast cell surface. CSU is a benign disease whose symptoms affect quality of life and has rarely complete remission in spite of antihistamines at high dose, and for second line Omalizumab (O) that costs 200 times as much and lead to complete remission in up to 70% of patients.
In a small international trial, the authors sought to compare the efficacy and safety of L with O and placebo in patients who have moderate-to-severe CSU inadequately controlled. They randomly assigned patients to receive L at a dose of 24 mg, 72 mg, or 240 mg, O. at a dose of 300 mg, or placebo, administered subcutaneously every 4 weeks for a period of 20 weeks, and a single 120-mg dose of L.
Disease symptoms of hives, itch, and angioedema were monitored by means of weekly activity scores. The main objective was to determine a dose–response relationship for the complete control of hives. The primary end point of this response was assessed at week 12. A total of 382 patients underwent randomization.
Results: at week 12, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of L had complete control of hives, as compared with 26% of the patients in the O group and no patients in the placebo group.
In this small and short trial, no safety concerns regarding L or O emerged.
In conclusion a higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with L therapy of 72 mg or 240 mg than with O or placebo. Many questions remain: the effect of single dose of 120mg of L lasts as long as 8 weeks. So larger trials are needed and more effective anti-IgE are waited. In this respect Dupilumab seems to have also an excellent profile.


 

Variations of inhaled corticoids treatment inadequately controlled asthma
Wechsler M et al. NEJM Sept 26 381 1227-1239
Virchow JC et al. The Lancet: 30 Sept 2019 "First online"

 1) Among black patient morbidity from asthma is disproportionately higher than among white. In two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults, at least one grandparent was identified as black and had asthma that was uncontrolled with low-dose inhaled glucocorticoids. After compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up which double to quintuple the dose of fluticasone, (to 250 μg twice a day) was compared with adding salmeterol (50 μg twice a day) and doubling the fluticasone (to 100 μg twice a day). A superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P=0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone [P=0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments.

2) Single inhaler Triple therapy in Uncontrolled Asthma
Two parallel-group, double-blind, randomized trials (Double : (BDP): beclomethasone dipropionate + LABA (Formol Fumarate: FF) [TRIMARAN] and Triple BDP +FF + Tiotropium [TRIGGER]) were respectively recruited from 171 sites across 16 countries and from 221 sites across 17 countries. Eligible patients were adults (aged 18–75 years), had a history of one or more exacerbations in the previous year, randomly assigned to treatment: 52 weeks, using an interactive response technology system stratified by country. Coprimary endpoints for both trials FEV 1 at week 26 and rate of moderate and severe exacerbations over 52 weeks. Safety was assessed in all patients. These 2 groups were compared when a long acting muscarinic antagonist (Glycopyrronium) was added to treatment in a single inhaler.
In patients of TRIMARAN group: 579 were given BDP/FF/+G and 576 were given BDP/FF. Among 1437 patients in TRIGGER group were given BDP/FF/G (n=573), BDP/FF (n=576), or BDP/FF plus tiotropium (n=288). Compared with the BDP/FF group, FEV 1 improved in the BDP/FF/G group by 57 mL in TRIMARAN and by 73 mL in TRIGGER, with reductions in the rate of moderate and severe exacerbations of 15% and 12%.
Four patients had serious adverse events, leading to death. None of the deaths were considered as related to treatment. In conclusion, addition of a long-acting muscarinic antagonist to inhaled corticosteroid plus long-acting β 2-agonist therapy improves lung function and reduces exacerbations in uncontrolled asthma.

 
Your comments and questions are welcome at the following addresses:
Claude Molina - claude.nelly.molina@orange.fr                                                     
Jacques Gayraud - gayraud65@wanadoo.fr

eaaci register here C
*register to receive the bibliographic updates via email

 
Last updated 23 October 2019
Privacy Policy - disclaimer

EAACI recently updated its privacy policy and would like to highlight some key bits of information with you.

  • EAACI does not distribute, share or sell your information;
  • For technical and administrative purposes some information that can be used to identify you may be forwarded to third parties. For example, to process your registration for the EAACI Annual Congress and other EAACI events;
  • The Academy may also send you e-mail messages with news from the society. If you would like to no longer receive them, you can unsubscribe at any time by using the unsubscribe link in any of our communications;
  • You may also update your preferences or your profile information at any time by contacting us.

To continue please confirm that you agree with our updated privacy policy.

Thank you!

You have successfully agreed the new privacy policy – disclaimer.

Thank you!

You disagreed with the new privacy policy – disclaimer and your feedback will be reviewed as soon as possible.

Agree & Continue
Disagree
Send feedback
Cancel