To the editor,
An increasing body of evidence strongly suggests that immunoglobulin E
(IgE) plays a key role in cancer immune surveillance. Moreover, a
possible link between absent or very low serum IgE levels and malignancy
risk has also been suggested 1. Still, two studies on
omalizumab, a widely used anti-IgE drug, failed to suggest any influence
on the development or progression of malignancy 2,3.
However, they were based on the analysis of data from efficacy clinical
trials, including carefully selected participants, enrolled for a
limited time, and neither powered nor designed to assess long-term
complications such as incident cancer. Therefore, we aimed to examine
the incidence of malignancy using comprehensive data from real-life
omalizumab-treated patients.
We performed a disproportionality analysis (case/non-case
study)4 within VigiBase, the World Health
Organization’s global database of individual case safety reports, to
identify a signal of cancer, expressed as the reporting odds-ratio
[ROR] and its 95% confidence interval [CI] for
omalizumab.5 Cases were defined as Adverse Drug
Reactions (ADR) coded as Neoplasms according to the Medical Dictionary
for Regulatory Activities (MedDRA) terminology reported between 2000 and
2020. Non-cases were defined as all other ADRs during the same period.
The main analysis estimated the risk of reporting “Neoplasms”
associated with Omalizumab compared with all other ADRs for Omalizumab
to the remaining reported drugs. Analysis for other selected cancers
according to MedDRA terminology was also performed.
A total of 1380 reports mentioned neoplasms associated with omalizumab.
The disproportionality signal was significant and positive: ROR
[95%CI] = 1.65 [1.56 to 1.74]. (Table 1). The association was
particularly strong in breast and lung cancer, with 232 cases and ROR
[95%CI] = 4.12 [3.61-4.69] and, 85 cases and ROR [95%CI] =
3.04 [2.45-3.76] respectively (Table 1).
The finding that omalizumab increases by two-thirds the risk of incident
cancer is of major relevance but should be interpreted with caution.
Disproportionality analysis is exploratory in the context of signal
detection, not allowing quantification of the true risk. These studies
have been shown to detect early signals that later are confirmed by
controlled studies.4 As such, a confirmatory study is
needed to ascertain our findings. Information present in VigiBase comes
from a variety of sources and the probability that the suspected adverse
effect is drug-related is not the same in all cases. Additionally,
under-reporting may have occurred. However, when referring to serious
events, like cancer, this is less prone to happen and, if it did, would
increase the strength of the signal. Similarly, the notoriety effect
cannot apply as former studies failed to show any association between
omalizumab and cancer.
Our study has important strengths. Our analysis was based on the most
global and comprehensive pharmacovigilance database. Moreover, the
safety of omalizumab was evaluated using post-marketing surveillance
data overcoming the limitations of clinical trials inclusion criteria
and limited follow-up.
In conclusion, using real-world data mining, we reported a signal that
omalizumab may be associated with a significantly higher risk of
malignancies. Until further studies confirm the long-term safety of
omalizumab, this observation should be reflected on the benefit-risk
assessment when considering anti-IgE for the treatment of allergic
conditions.