A meta‐analysis on allergen‐specific immunotherapy using MCT^® (MicroCrystalline Tyrosine)‐adsorbed allergoids in pollen allergic patients suffering from allergic rhinoconjunctivitis

Abstract

Background The World Allergy Organization and the European Academy of Allergy and Clinical Immunology recommend to perform product‐specific meta‐analyses for allergen‐specific immunotherapies because of the high degree of heterogeneity between individual products. This meta‐analysis evaluates the efficacy and safety of Glutaraldehyde‐modified and MCT® (MicroCrystalline Tyrosine)‐adsorbed allergoids (MATA). Methods The databases MEDLINE, LILACS, embase, LIVIVO, Web of Science and Google (Scholar) were searched for publications on MATA up to June 2019. Primary endpoint was the combined symptom and medication score (CSMS). Secondary endpoints were single scores, immunogenicity and improvement of allergic condition. Secondary safety endpoints were the occurrence of side effects. A random effects model was applied with (standardized) mean differences ([S]MDs) including confidence intervals (CI). Heterogeneity was analyzed using the I2 index and publication bias using Egger's test and Funnel plots. Subgroups were analyzed regarding age and asthma status. Results Eight randomized double‐blind placebo‐controlled trials were selected for efficacy and 43 publications for safety analysis. In total, 4531 patients were included in this analysis including eight studies containing data on children and adolescents. AIT with MATA significantly reduced allergic symptoms and medication use with a SMD for CSMS of −0.8 (CI: −1.24, −0.36) in comparison to placebo. Heterogeneity was moderate between the studies. The total symptom score (−1.2 [CI: −2.11, −0.29]) and the total medication score (−2.2 [CI: −3.65, −0.74]) were also significantly reduced after MATA treatment. Patient's condition improved significantly after treatment with MATA, with an odds ratio of 3.05 (CI: 1.90, 4.90) when compared to placebo. The proportion of patients, who developed side effects was 38% (CI: 19%, 57%). No serious side effects occurred. Safety in the subgroups of asthmatic patients, children and adolescents did not differ from the overall patient population. Conclusions This meta‐analysis reveals a large body of evidence from publications investigating MATA. MATA significantly improved allergic symptoms and reduced the use of anti‐allergic medication in comparison to placebo, with an excellent safety profile. Especially for children and asthmatic patients, the use of MATAs can be considered as safe, because the safety profiles in these groups did not differ from the total patient population.

Allergen Immunotherapy: Current and Future Trends

“…MCT has not shown toxic properties, although it is contraindicated in tyrosine metabolism disorders [ 90 ]. Currently, MCT is patented as an adjuvant for use in immunotherapy [ 93 ] and is integrated into glutaraldehyde allergoids for Dermatophagoides to help reduce allergic symptoms and diminish the use of relief drugs [ 94 , 95 , 96 , 97 ].…”

MicroCrystalline Tyrosine-adsorbed immunotherapy

“…As Allergoid-MCT has been marketed for decades, many clinical studies including DBPC trials have been conducted since their introduction on the market. A recently published meta-analysis undertaken by Becker et al [ 33 ▪ ] provides an overview about the evidence generated since the 1970s. These data formally fulfil the highest standard for the level of evidence (1A) according to the European Academy of Allergy and Clinical Immunology (EAACI), because they are based on a systematic literature review and meta-analysis [ 34 ].…”

“…These data formally fulfil the highest standard for the level of evidence (1A) according to the European Academy of Allergy and Clinical Immunology (EAACI), because they are based on a systematic literature review and meta-analysis [ 34 ]. It is focused on MCT-adsorbed pollen allergoids and clearly demonstrates a significant improvement in allergic symptoms and a reduction in the use of antiallergic medication when compared with placebo, together with an excellent safety profile [ 33 ▪ ]. The analysis included, among other randomized controlled trials (RCTs), controlled trials and noncontrolled studies, eight double-blind placebo-controlled trials (DBPCs) with a total of 884 patients with seasonal allergic rhinoconjunctivitis.…”

“…Although those DBPC trials were published between 1974 and 1995, they were state-of-the-art when conducted. Evaluating the quality of those trials today, six out of eight trials proved to be sufficient and met the current standard [ 33 ▪ ].…”

Major Allergen Content in Allergen Immunotherapy Products: The Limited Value of Numbers

“…For decades, allergen immunotherapy (AIT) has been used for the treatment of allergic rhinitis and rhinoconjunctivitis, asthma, and venom allergy. At present, AIT is supported by data accumulated from large, double-blind, placebo-controlled clinical trials demonstrating efficacy and safety [4][5][6][7][8][9][10][11], as well as a high number of noninterventional studies, systematic reviews and meta-analyses [12][13][14], and real-world evidence [15][16][17][18][19]. Among its benefits, it has been demonstrated that AIT may prevent the development of asthma in children with allergic rhinitis [8].…”