DISCUSSION
In this systematic review and meta-analysis we evaluated the efficacy and safety of omalizumab in the treatment of AR. Our systematic review retrieved 12 RCTs, with a total of 3,211 patients. The meta-analysis showed that, treatment with omalizumab significantly improved the nasal and ocular symptom scores, as well as the disease-specific quality of life and reduced the need of rescue medication in patients with AR, without any signal for increased adverse events compared to placebo.
We observed that the improvement in nasal symptom score was higher in the 3 cedar pollen-induced allergic rhinitis trials, which were conducted in Japan, and particularly in two of them13, 14 this improvement between treatment groups exceeded the previously reported minimal clinically relevant difference (MCID) of 0.87 points17. Cedar pollinosis constitutes an important medical problem in Japan. Its prevalence was increased by almost 10% from 1998 (19.6%) to 2008 (29.8%) 18. Furthermore, a more recent study indicated that the prevalence of Cedar pollinosis in Japan had been estimated to be over 40%19. Importantly, approximately 50% of patients with diagnosed cedar pollinosis develop severe seasonal symptoms, with a significant impact on their daily lives and the need for additional treatments20. The greater efficacy of anti-IgE treatment in patients with cedar pollinosis may reflect the significant burden of disease and the central role of IgE in this form of allergic rhinitis.
Omalizumab treatment reduced significantly the daily use of rescue medication and improved quality of life compared to placebo. The overall mean improvement in RQoL of 0.45 points was close to the minimal clinically important difference that has been previously reported as being 0.5 points17. Interestingly, the mean treatment effect of omalizumab on RQoL in two of the trials that assessed this outcome14, 15 exceeded the minimal clinically important difference (reaching -0.55 and -0.51 points respectively).
The comparator of omalizumab was placebo in all but one of the earlier trials12 in which suplatast tosilate was given to the patients randomized in the control arm, while in 4 other trials10, 11, 21, 22, the patients received a specific allergen immunotherapy. More importantly, in the trial by Okubo and co-authors 202014, the latest of the omalizumab trials in patients with cedar pollinosis, patients received concomitant standard-of-care medications (antihistamines and nasal corticosteroids) in both treatment arms (omalizumab and placebo). As previously mentioned, in this trial, the mean effect of omalizumab exceeded the MCID for daily nasal symptoms score and for rhinitis-related quality of life, suggesting clinically relevant efficacy of omalizumab on top of standard-of-care medication in a severe form of the disease that significantly impacts the daily life of patients. Based on the results of the study by Okubo and colleagues14, omalizumab was approved23 for severe seasonal AR that is inadequately controlled by standard-of-care medication in Japan. In the same line, a recent meta-analysis included 16 RCTs of patients with poorly controlled seasonal and perennial AR and showed that the omalizumab had a statistically significant difference in reduced use of rescue drugs, improved symptoms, and improved quality of life 24. However, this meta-analysis does not include the recent study from Okubo and colleagues14 that was a large trial with intense treatment in the control arm.
Overall, the results of the present meta-analysis further support the conclusions of our previous work6, reinforcing them by the inclusion of an important number of more recent studies involving a significantly larger number of participants. The fact that omalizumab continues to present a comparable adverse effects profile to placebo, combined with superior efficacy, further supports a favorable benefit-risk profile for this medication in patients with severe AR inadequately controlled with conventional treatments.
Our study has certain limitations. Firstly, considerable between-study heterogeneity was observed. This was expected due to the different populations of which, our included trials were consisted of. As mentioned before, the improvement of nasal symptom score was higher in the 3 trials that held in Japan, where the AR prevalence and severity, especially in the form of cedar pollinosis, is higher. Additionally, differences in the baseline severity of the disease; different prevalence of patients with other comorbidities, such as asthma, conjunctivitis, and atopic dermatitis; difficulties in the comparability of different scores used; differences in omalizumab dose and dosing may have limited the accuracy of this meta-analysis Finally, our findings come from published RCTs, thereby excluding real world evidence, like the recently published paper by Cavaliere and co-workers on long term efficacy of omalizumab in AR25. Furthermore, publication and language bias is a major concern when dealing with efficacy trials.
In conclusion, in this meta-analysis we have demonstrated that treatment with omalizumab in patients with allergic rhinitis significantly improved the nasal and ocular symptom scores and QoL, reduced the use of rescue medication, with a safety profile comparable to placebo. Our findings further support the efficacy and safety of omalizumab in the management of patients with allergic rhinitis inadequately controlled with conventional treatment. The potential benefits of omalizumab need to be considered in the context of access of therapy and cost effectiveness.