Omalizumab para la rinosinusitis cr�nica

Bra�es, Roc�o; Rosenbaum, Andr�s; Callejas, Claudio; Winter, Mat�as

doi:10.5867/medwave.2018.07.7346

Res�menes Epistemonikos

Medwave 2018;18(7):e7346 doi: 10.5867/medwave.2018.07.7346

Omalizumab para la rinosinusitis cr�nica

Omalizumab for chronic rhinosinusitis

Roc�o Bra�es, Andr�s Rosenbaum, Claudio Callejas, Mat�as Winter

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Palabras clave: Chronic rhinosinusitis, omalizumab, Epistemonikos, GRADE.

Abstract

INTRODUCTION
Chronic rhinosinusitis is a high prevalence chronic inflammatory disease that involves nasal mucosa and paranasal sinuses. Immunoglobulin E is an inflammatory mediator that plays an etiopathogenic role in this condition, so omalizumab, an anti-immunoglobulin E monoclonal antibody, might be a therapeutic alternative.

METHODS
We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach.

RESULTS AND CONCLUSIONS
We identified five systematic reviews that included five primary studies overall, of which two correspond to randomized trials. We concluded it is not clear whether omalizumab leads to an improvement in the nasal polyps scale, quality of life, general well-being or nasal symptoms in patients with chronic rhinosinusitis, because the certainty of the evidence is very low. On the other hand, omalizumab is probably associated with frequent adverse effects.

Problem

Chronic rhinosinusitis is an inflammatory disease of the mucosa of the nasal cavity and paranasal sinuses lasting longer than 12 weeks. It is a common disease that could affect more than 15% of the total population in the United States [1], which is why it is an important health problem that affects quality of life. Although there are therapeutic alternatives, a group of patients remains symptomatic. It has been suggested that this may be due to most treatments focusing on relief of symptoms and reduction of inflammation, rather than in the cause. Current research has changed the approach to target barrier responses and states of chronic inflammation [2].

Omalizumab is a humanized monoclonal antibody that selectively binds to the crystallizable fragment (Fc) region of immunoglobulin E (IgE) by reducing free immunoglobulin E, which produces an anti-inflammatory effect and apoptosis of eosinophils. However, it is not clear to what extent this is translated into a clinical effect.

Methods

We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others, to identify systematic reviews and their included primary studies. We extracted data from the identified reviews and reanalyzed data from primary studies included in those reviews. With this information, we generated a structured summary denominated FRISBEE (Friendly Summary of Body of Evidence using Epistemonikos) using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies when it is possible, a summary of findings table following the GRADE approach and a table of other considerations for decision-making.

Key messages

It is not clear whether omalizumab leads to an improvement in the Nasal Polyps Score, quality of life, general well-being or nasal symptoms in chronic rhinosinusitis, because the certainty of the evidence is very low.
Omalizumab is probably associated with frequent adverse effects.

About the body of evidence for this question

What is the evidence. See evidence matrix in Epistemonikos later	We found five systematic reviews [3],[4],[5],[6],[7],[8] that included five primary studies [9],[10],[11],[12],[13] of which two correspond to randomized controlled trials [9],[12]. This table and the summary in general are based on the two randomized trials [9],[12], given the observational studies did not increase the certainty of the existing evidence or provide relevant additional information.
What types of patients were included*	Both trials included patients older than 18 years [9],[12]. One trial evaluated patients suffering from chronic rhinosinusitis with nasal polyps and asthma for more than 2 years [12], and the other trial evaluated patients after sinus surgery [9].
What types of interventions were included*	All trials used omalizumab as an intervention. One trial administered omalizumab 150-375 mg every 2 weeks [12] and another 0,016 mg/kg once a month [9]. Both trials compared the intervention against placebo.
What types of outcomes were measured	The trials evaluated multiple outcomes, which were grouped by the systematic reviews as follows: Nasal Polyp Scale (Nasal Polyp Score - NPS) Nasal symptoms- Quality of life and general well-being Adverse effects: such as headache, nasal obstruction, shortness of breath, allergies, common cold, gastroenteritis, otitis media, shoulder of pain and left ulnar hypoaesthesia. The average follow-up was 12.9 months, with a range between 5 and 28 months.

* The information about primary studies is extracted from the systematic reviews identified, unless otherwise specified.

Summary of findings

The information on the effects of omalizumab in chronic rhinosinusitis is based on two randomized trials that included 38 patients [9],[12].

Both trials reported the effect on the Nasal Polyp Score (31 patients), changes in quality of life (38 patients) and nasal symptoms (38 patients) [9],[12]. Only one trial reported adverse effects (24 patients) [12].

The summary of findings is as follows:

It is not clear whether omalizumab leads to an improvement in the Nasal Polyps Score in chronic rhinosinusitis because the certainty of the evidence is very low.
It is not clear whether omalizumab leads to an improvement in quality of life and general well-being because the certainty of the evidence is very low.
It is not clear whether omalizumab leads to an improvement in nasal symptoms (nasal obstruction, loss of sense of smell and presence of rhinorrhea) because the certainty of the evidence is very low.
Omalizumab probably has adverse effects in patients with chronic rhinosinusitis. The certainty of the evidence is moderate.

Follow the link to access the interactive version of this table (Interactive Summary of Findings – iSoF)

Other considerations for decision-making

To whom this evidence does and does not apply

The conclusions of this summary apply to adults patients with chronic rhinosinusitis.
Due to the limitations of the identified evidence, it is not possible to draw conclusions about whether there is a subgroup of patients that especially benefits from the intervention.

About the outcomes included in this summary

Among the outcomes evaluated in the table are those considered critical for decision making, according to the opinion of the authors of this summary.
It was decided to focus on the changes in the nasal polyps scale, which is an outcome widely used in the clinic, and for which the trials provided the necessary information to conduct a meta-analysis.
Although both trials included changes in computed tomography of paranasal cavities within their outcomes, it was decided not to include them in the summary of findings table because it is a surrogate outcome.

Balance between benefits and risks, and certainty of the evidence

It is not possible to make an adequate balance between the risks and benefits of omalizumab in patients with chronic rhinosinusitis, due to the uncertainty about the benefits.
On the other hand, although the trials have a small sample size, the evidence is sufficient to conclude that the adverse effects are probably frequent.

Resource considerations

Omalizumab is a high-cost intervention, so it is particularly important for decision making to have accurate information about the benefits. Given the uncertainty associated with the benefits, it is not possible to make an adequate estimation of the cost-benefit.

What would patients and their doctors think about this intervention

Faced with the evidence presented in this summary, most clinicians and patients should lean against the use of omalizumab as the first therapeutic line in chronic rhinosinusitis, mainly due to the uncertainty about its benefit, its cost and the frequency of adverse effects.
However, in refractory cases or with comorbidities, it is likely that some people may be inclined to use it, especially if there are no resource constraints.

Differences between this summary and other sources

This summary presents concordant conclusions with those of the six systematic reviews identified [3],[4],[5],[6], [7],[8].
The conclusions of this summary agree with the European Consensus on Rhinosinusitis and Nasal Polyps 2012 [2].

Could this evidence change in the future?

It is very likely that future evidence will change the conclusions of this summary, due to the uncertainty about the benefits.
We identified three ongoing trials in the International Clinical Trials Registry Platform of the World Health Organization on the use of Omalizumab in chronic rhinosinusitis with polyps [14],[15],[16].
No systematic reviews in progress were found in the PROSPERO database (International Prospective Register of Systematic Reviews).

How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Omalizumab for chronic rhinosinusitis.

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier.

After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

This article is part of the Epistemonikos Evidence Synthesis project. It is elaborated with a pre-established methodology, following rigorous methodological standards and internal peer review process. Each of these articles corresponds to a summary, denominated FRISBEE (Friendly Summary of Body of Evidence using Epistemonikos), whose main objective is to synthesize the body of evidence for a specific question, with a friendly format to clinical professionals. Its main resources are based on the evidence matrix of Epistemonikos and analysis of results using GRADE methodology. Further details of the methods for developing this FRISBEE are described here (http://dx.doi.org/10.5867/medwave.2014.06.5997)

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

Potential conflicts of interest

The authors do not have relevant interests to declare.

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