Efficacy and safety of intralymphatic immunotherapy in allergic rhinitis: A systematic review and meta-analysis

Nor Rahimah Aini, Norhayati Mohd Noor, Mohd Khairi Md Daud, Sarah K Wise, Baharudin Abdullah, Nor Rahimah Aini, Norhayati Mohd Noor, Mohd Khairi Md Daud, Sarah K Wise, Baharudin Abdullah

Abstract

Background: Intralymphatic immunotherapy (ILIT) is a potential treatment option for allergic rhinitis (AR). We aimed to determine the efficacy (primary outcomes) and safety (secondary outcomes) of ILIT in treating patients with AR.

Methods: An electronic literature search was performed using MEDLINE and Cochrane Central Register of Controlled Trials CENTRAL (from their inception to December 2020). A random-effects model was used to estimate the pooled prevalence with 95% confidence intervals. This study is registered with PROSPERO (CRD42019126271).

Results: We retrieved a total of 285 articles, of which 11 satisfied our inclusion criteria. There were 452 participants with age ranged from 15 to 58 years old. Intralymphatic immunotherapy was given in three doses with intervals of four weeks between doses in 10 trials. One trial gave three and six doses with an interval of two weeks. Both primary and secondary outcomes showed no difference between ILIT and placebo for all trials. There was no difference in the combined symptoms and medication score (SMD -0.51, 95% CI -1.31 to 0.28), symptoms score (SMD -0.27, 95% CI -0.91 to 0.38), medication score (SMD -6.56, 95% CI -21.48 to 8.37), rescue medication (RR 12.32, 95% CI 0.72-211.79) and the overall improvement score (MD -0.07, 95% CI -2.28 to 2.14) between ILIT and placebo. No major adverse events noted.

Conclusions: Intralymphatic immunotherapy possibly has a role in the treatment of AR patients. This review found it is safe but not effective, which could be contributed by the high variation amongst the trials. Future trials should involve larger numbers of participants and report standardized administration of ILIT and outcome measures.

Keywords: allergen‐specific immunotherapy; allergic rhinitis; efficacy; intralymphatic immunotherapy; safety.

Conflict of interest statement

Sarah K. Wise is a consultant for NeurENT, Stryker and advisory board member for OptiNose, SinopSys Surgical, ALK‐Abello, Genentech. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

© 2021 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.

Figures

FIGURE 1
FIGURE 1
Study flow diagram
FIGURE 2
FIGURE 2
Risk of bias summary for individual study
FIGURE 3
FIGURE 3
Primary outcomes of intralymphatic immunotherapy versus placebo
FIGURE 4
FIGURE 4
Secondary outcomes (adverse events) of intralymphatic immunotherapy versus placebo
FIGURE 5
FIGURE 5
Secondary outcomes (quality of life) of intralymphatic immunotherapy versus placebo

References

    1. Bousquet J, Khaltaev N, Cruz AA, et al. Allergic rhinitis and its impact on asthma (ARIA) 2008. Allergy. 2008;63:8‐160.
    1. Asher MI, Montefort S, Bjorksten B, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross‐sectional surveys. Lancet. 2006;368(9537):733‐743.
    1. Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases A WHO position paper. J Allergy Clin Immunol. 1998;102(4 Pt 1):558‐562.
    1. Price D, Bond C, Bouchard J, et al. International primary care respiratory group (IPCRG) guidelines: management of allergic rhinitis. Prim Care Respir J. 2006;15(1):58‐70.
    1. Scadding G, Durham S, Mirakian R, et al. BSACI guidelines for the management of allergic and non‐allergic rhinitis. Clin Exp Allergy. 2008;38(1):19‐42.
    1. Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst Rev. 2007;2007(1):CD001936.
    1. Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;127(Suppl 1):S1‐S55.
    1. Canonica GW, Bousquet J, Casale T, et al. Sub‐lingual immunotherapy: World allergy organization position paper 2009. World Allergy Organ J. 2009;2:233‐281.
    1. Johansen P, Haffner A, Koch F, et al. Direct intralymphatic injection of peptide vaccines enhances immunogenicity. Eur J Immunol. 2005;35(2):568‐574.
    1. Hylander T, Latif L, Petersson‐Westin U, Cardell LO. Intralymphatic allergen‐specific immunotherapy: an effective and safe alternative treatment route for pollen‐induced allergic rhinitis. J Allergy Clin Immunol. 2013;131(2):412‐420.
    1. Senti G, Prinz Vavricka BM, Erdmann I, et al. Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial. Proc Natl Acad Sci U. S. A. 2008;105(46):17908‐17912.
    1. Senti G, Crameri R, Kuster D, et al. Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections. J Allergy Clin Immunol. 2012;129(5):1290‐1296.
    1. Witten M, Malling HJ, Blom L, Poulsen BC, Poulsen LK. Is intralymphatic immunotherapy ready for clinical use in patients with grass pollen allergy? J Allergy Clin Immunol. 2013;132(5):1248‐1252.e5.
    1. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group . Preferred reporting items for systematic reviews and meta‐analyses: the PRISMA statement. Ann Intern Med. 2009;151:264‐269, w64.
    1. GRADEpro G . Computer Program on . Version [July, 2016]. McMaster University; 2014.
    1. Higgins JP, Green S, eds. Cochrane handbook for systematic reviews of interventions. Wiley; 2011.
    1. Collaboration C . Review Manager (RevMan) Version 5.3. Copenhagen: The Nordic Cochrane Centre; 2014.
    1. Patterson AM, Bonny AE, ShielsWE, 2nd, Erwin EA. Three‐injection intralymphatic immunotherapy in adolescents and young adults with grass pollen rhinoconjunctivitis. Ann Allergy Asthma Immunol. 2016;116(2):168‐170.
    1. Schmid JM, Nezam H, Madsen HH, Schmitz A, Hoffmann HJ. Intralymphatic immunotherapy induces allergen specific plasmablasts and increases tolerance to skin prick testing in a pilot study. Clin Transl Allergy. 2016;6:19.
    1. Lee SP, Choi SJ, Joe E, et al. A pilot study of intralymphatic immunotherapy for house dust mite, cat, and dog allergies. Allergy Asthma Immunol Res. 2017;9(3):272‐277.
    1. Ahlbeck L, Ahlberg E, Nystrom U, Bjorkander J, Jenmalm MC. Intralymphatic allergen immunotherapy against pollen allergy: a 3‐year open follow‐up study of 10 patients. Ann Allergy Asthma Immunol. 2018;121(5):626‐627.
    1. Weinfeld D, Westin U, Hellkvist L, Mellqvist UH, Jacobsson I, Cardell LO. A preseason booster prolongs the increase of allergen specific IgG4 levels, after basic allergen intralymphatic immunotherapy, against grass pollen seasonal allergy. Allergy Asthma Clin Immunol. 2020;16:31.
    1. Hylander T, Larsson O, Petersson‐Westin U, et al. Intralymphatic immunotherapy of pollen‐induced rhinoconjunctivitis: a double‐blind placebo‐controlled trial. Respir Res. 2016;17:10.
    1. Hellkvist L, Hjalmarsson E, Kumlien Georen S, et al. Intralymphatic immunotherapy with 2 concomitant allergens, birch and grass: a randomized, double‐blind, placebo‐controlled trial. J Allergy Clin Immunol. 2018;142(4):1338‐1341.e9.
    1. Konradsen JR, Grundstrom J, Hellkvist L, et al. Intralymphatic immunotherapy in pollen‐allergic young adults with rhinoconjunctivitis and mild asthma: a randomized trial. J Allergy Clin Immunol. 2020;145(3):1005‐1007.
    1. Skaarup SH, Schmid JM, Skjold T, Graumann O, Hoffmann HJ. Intralymphatic immunotherapy improves grass pollen allergic rhinoconjunctivitis: a 3‐year randomized placebo‐controlled trial. J Allergy Clin Immunol. 2020;S0091‐6749(20):30964‐30967.
    1. Thompson CP, Silvers S, Shapiro MA. Intralymphatic immunotherapy for mountain cedar pollinosis: a randomized, double‐blind, placebo‐controlled trial. Ann Allergy Asthma Immunol. 2020;125(3):311‐318.
    1. Terada T, Omura S, Kikuoka Y, et al. Sustained effects of intralymphatic pollen‐specific immunotherapy on Japanese cedar pollinosis. Rhinology. 2020;58(3):241‐247.
    1. Juniper EF, Guyatt GH. Development and testing of a new measure of health status for clinical trials in rhinoconjunctivitis. Clin Exp Allergy. 1991;21(1):77‐83.
    1. Juniper EF, Guyatt GH, Epstein RS, Ferrie PJ, Jaeschke R, Hiller TK. Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials. Thorax. 1992;47(2):76‐83.
    1. Canonica GW, Baena‐Cagnani CE, Bousquet J, et al. Recommendations for standardization of clinical trials with Allergen Specific Immunotherapy for respiratory allergy. A statement of a World Allergy Organization (WAO) taskforce. Allergy. 2007;62(3):317‐324.
    1. Hoang MP, Seresirikachorn K, Chitsuthipakorn W, Snidvongs K. Intralymphatic immunotherapy for allergic rhinoconjunctivitis: a systematic review and meta‐analysis. Rhinology. 2021;59(3). 10.4193/Rhin20.572

Source: PubMed

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