Brave new world of immunotherapy - Twitter summary from 2014 #ACAAI meeting

Dr Hal Nelson discussed whether to "retire" traditional SCIT in favor of SLIT drops, rush and cluster SCIT. Dr Hal Nelson offered his insights about the future of immunotherapy now that SLIT tablets are here.

Rush IT works but adverse reactions still remain in the double digits even with pre-medication.

Cluster IT
involves multiple injections in one day. It gets patients to maintenance and symptom relief quicker and is generally safe. Cluster immunotherapy - 15 injections over 6 wks vs. 13 injections over 13 weeks, the rates of systemic reactions were similar (3% and 4%). Systemic reaction rates to Rush IT protocols are still in double digits even with aggressive pretreatment with H1 and H2 antagonists and steroids.

Ways to improve safety and convenience: omalizumab, SLIT, Intralymphatic, Epicutaneous or Intradermal IT.

Mechanisms of allergen-specific immunotherapy (click to enlarge the image). The diagram is based on: Mechanisms of allergen-specific immunotherapy. Akdis CA, Akdis M. J Allergy Clin Immunol. 2011 Jan;127(1):18-27.

Ragweed liquid sublingual SLIT data. JACI 133:751. Creticos et al. JACI 2014; 133:751-8 - First US report of the Ragweed SLIT drops, made by Greer - 429 subjects, 90% tolerated 50 Amb a 1. Total combined score was 20% lower in Ragweed SLIT drop group compared to placebo group. Dr Nelson commented that rates of local oral reactions appears lower with drops than with tablets. Relative cost of SCIT 12.5 Amb a 1 units/mo = $7.80/yr vs. SLIT 50 Amb a 1 u/d for 6 mo/y = $488/yr.

Amar et al studied multiple allergen SLIT - also drops - Timothy monotherapy was better than when mixed with other allergens.

- Epicutaneous allergen-specific IT - Sentri et al JACI 2011.

In epicutaneous IT, local reactions are common and 8% even experienced mild systemic reactions.

Intralymphatic immunotherapy - 3 injections at time 0, 4 wk and 8 wk were equivalent to 52-week, weekly SCIT for Timothy grass. The promise of intralymphatic immunotherapy was discussed in PNAS 2008 105: 17908. Dr Nelson showed the intralymphatic immunotherapy study again - 3 IL injections were better than standard SCIT with many more injections.  Benefits of intralymphatic immunotherapy persist 3 years post discontinuation. However, a follow up study giving IL injections q2wk failed to replicate the results of the initial study.

Dr Stephen Durham presented on why allergists should embrace SLIT.

Durham et al JACI 2006; 117: 802-09 - one of the first studies of the Grass SLIT product initially developed by ALK, now Merck's tab. The 5 grass pollen (300IR) product developed by @StallergenesCom is also effective with reduction in symptoms and medication use.

Both the @Merck grass SLIT and the @StallergenesCom grass SLIT tablets have shown safety and efficacy in children older than 5. Local side effects from these SLIT tablets common - 40% will experience oral itch, it usually goes away with 2 to 4 weeks of treatment.

Now on to ragweed SLIT-tablet, Dr Creticos was again the lead author, a tablet with 12 Amb a 1 was effective and tolerated. Use of ragweed SLIT was associated with lower rates of loratadine, mometasone and olopatadine, also lower symptom scores compared with placebo.

Reviewing recent history of SLIT literature shows efficacy. Dr Durham said ragweed SLIT probably works as well as intranasal steroids and better than antihistamines for symptom relief.

A recent JACI Phase II study of HDM SLIT tablet showed ability to reduce ICS while maintaining asthma control in DM allergic asthmatics. There was a reduction in daily dose of ICS by 100 mcg with HDM SLIT, according to this preliminary pilot study.

There is an exciting bold study ongoing in Europe - GAP-Grass SLIT given for 3 years to 800 children, the primary outcome is the time to first asthma episode. The GAP study will thus evaluate primary prevention - treating children with Grass Induced Allergic rhinitis, but no asthma, with SLIT.

Dr Durham believes the treatment effects between SCIT and SLIT are similar when you look at the well-designed 'big' trials. Immune tolerance network funded study of Durham's is comparing SCIT to SLIT in a head to head trial using NAC as outcome measure. SLIT tablet use is associated with increased IL-10 and TGF-B production, reflecting likely engagement of regulatory T cells. SLIT tablets also show persistent immunologic effects with increases in specific IgG4 even 2 years after stopping a 3 yr course of treatment.

Dr Durham: At this time, equipoise suggests that decision about SLIT vs SCIT should come down to patient preference.

Dr. David Bernstein discussed "Emerging Immunotherapies - Will we 'cure' allergies?" Dr Bernstein is already giving take home message - to say we will cure allergies is premature.

Limitations of SCIT include long duration of treatment, several allergens are non-standardized and not well studied, risk of anaphylaxis.

He discussed allergoids, fusion molecules, peptide immunotherapy, and recombinant vaccines.

Allergoids are modified allergens complexed to aldehydes. They are used via SCIT to reduce adverse reactions and preserve allergenicity.

Allergoids are allergens chemically modified with gluteraldehyde or formaldehyde - thye have reduced IgE binding but maintained immunogenecity. Allergoids are then linked to adjuvants such as aluminum hydroxide or tyrosine. These are used as "pre-seasonal" injections. Studies conducted had small numbers of patients but rates of systemic reactions were low.

Non-adjuvant virus-like particles coupled to Der p1 were shown to stimulate B cells to induce strong IgG responses (no clinical trials though). Other experimental approaches include fusion protein of Fel d1 with FcGamma - this inhibits mast-cell signaling (no clinical trials yet).

Phase III trials are underway for synthetic immunoregulatory epitopes "peptide immunotherapy" or SPIREs. Cat, Grass and HDM thus far. 

Recombinant Bet v 1 vaccine is also developed for treatment of birch allergy - 8 SC build up doses are followed by 10 monthly maintenance. The 2 higher doses of recombinant Bet V 1 were associated with Grade 2 and 3 systemic reactions, however. 

This is a Twitter summary from 2014 #ACAAI meeting. The post is a part of series. See the rest here:

The Twitter summary was made possible by @DrAnneEllis and @MatthewBowdish

Several allergists did a great job posting updates from the 2014 meeting of the #ACAAI. I used the website “All My Tweets” to review the tweets. For comparison, here are the tweets from previous #ACAAI meetings (scroll down the page for the past years):

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