Adverse reactions : תופעות לוואי

6 ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling: 
•   Infections [see Warnings and Precautions (5.1)]
•   Hypersensitivity Reactions [see Warnings and Precautions (5.2)] •   Infusion-Related Reactions [see Warnings and Precautions (5.3)] 
6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In clinical studies, the safety of VYVGART has been evaluated in 246 patients who received at least one dose of VYVGART, including 57 patients exposed to at least 7 treatment cycles and 8 patients exposed to at least 10 treatment cycles.

In a placebo-controlled study (Study 1) in patients with gMG, 84 patients received VYVGART 10 mg/kg [see Clinical Studies (14)]. Of these 84 patients, approximately 75% were female, 82% were White, 11% were Asian, and 8% were of Hispanic or Latino ethnicity. The mean age at study entry was 46 years (range 19 to 78).

The minimum time between treatment cycles, specified by study protocol, was 50 days. On average, VYVGART-treated patients received 2 cycles in Study 1. The mean and median times to the second treatment cycle were 94 days and 72 days from the initial infusion of the first treatment cycle, respectively, for VYVGART-treated patients.

Adverse reactions reported in at least 5% of patients treated with VYVGART and more frequently than placebo are summarized in Error! Reference source not found.. The most common adverse reactions (reported in at least 10% of VYVGART-treated patients) were respiratory tract infection, headache, and urinary tract infection.

Table 1: Adverse Reactions in ≥ 5% of Patients Treated with VYVGART and More Frequently than in Placebo-Treated Patients in Study 1 (Safety Population)
Adverse reaction                             VYVGART       Placebo
(N=84)     (N=83)
%           %
Respiratory tract infection                                               33          29 *
Headache                                                                  32          29 
Urinary tract infection                                                       10                       5 Paraesthesia†                                                                  7                       5 Myalgia                                                                        6                       1 *
Headache includes migraine and procedural headache.
†Paraesthesia includes oral hypoesthesia, hypoesthesia, and hyperesthesia.


6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of VYVGART. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Immune System Disorders: Hypersensitivity reactions including anaphylaxis and hypotension, and infusion- related reactions [see Warnings and Precautions (5.2, 5.3)].

6.3 Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to VYVGART in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

In up to 26 weeks of treatment in Study 1, 20% (17/83) of patients developed antibodies to VYVGART. Seven percent (6/83) of patients developed neutralizing antibodies.

Because few patients tested positive for anti-efgartigimod alfa antibodies and neutralizing antibodies, the available data are too limited to make definitive conclusions regarding immunogenicity and the effect on pharmacokinetics, safety, or efficacy of VYVGART.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il