Adverse reactions : תופעות לוואי

4.8   Undesirable effects
Summary of the safety profile

The most frequently reported adverse reactions observed were: headache (19.2%), arthralgia (13.5%), white blood cell count decreased (13.5%), hyperlipidaemia (13.5%), and injection-related reactions (12.5%).

Tabulated list of adverse reactions

Table 3 summarises the adverse reactions that have been reported in association with the use of satralizumab as a monotherapy or in combination with IST in clinical trials.

Adverse reactions from clinical trials (Table 3) are listed by MedDRA system organ class. Adverse reactions are presented using number of adverse events per 100 patient years and by frequency figures.
The corresponding frequency category for each adverse reaction is based on frequency figures and the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000).

Table 3: Adverse reactions

System Organ Class                                         Frequency
Very common                  Common
Blood and lymphatic system disorders                                       Hypofibrinogenaemia Metabolism and nutrition disorders          Hyperlipidaemia
Psychiatric disorders                                                      Insomnia Nervous system disorders                    Headache                       Migraine Cardiac disorders                                                          Bradycardia Vascular disorders                                                         Hypertension Respiratory, thoracic and mediastinal                                      Allergic rhinitis disorders
Gastrointestinal disorders                                                 Gastritis Skin and subcutaneous tissue disorders                                     Rash, pruritus
Musculoskeletal and connective tissue       Arthralgia                     Musculoskeletal stiffness disorders
General disorders and administration site   Injection-related reactions    Peripheral oedema conditions
Investigations                              White blood cell count         Neutrophil count decreased                      decreased platelet count decreased,
transaminases increased,
blood bilirubin increased,
weight increased

Description of selected adverse reactions

Injection-related reactions (IRRs)
IRRs reported in patients treated with satralizumab were predominantly mild to moderate, and most occurred within 24 hours after injections. The most commonly reported systemic symptoms were diarrhoea and headache. The most commonly reported local injection site reactions were flushing, erythema, pruritus, rash and pain.



Body weight

In the double-blinded treatment period, body weight increase ≥15% from baseline were observed in 3.8% of patients treated with satralizumab (monotherapy or in combination with IST) as compared with 2.7% of patients receiving placebo (or plus IST).

Laboratory abnormalities

Neutrophils
In the double-blinded treatment period, decreased neutrophils were observed in 31.7% of patients treated with satralizumab (monotherapy or in combination with IST) as compared with 21.6% of patients receiving placebo (or placebo plus IST). The majority of neutrophil decreases were transient or intermittent.
9.6% of patients receiving satralizumab had neutrophils below 1 x 109/L, compared with 5.4% receiving placebo (or placebo plus IST).

Platelets
In the double-blinded treatment period, decreases in platelet count (below 150 × 109/l) occurred in 24.0% of patients on satralizumab (monotherapy or in combination with IST) as compared with 9.5% of patients receiving placebo or placebo plus IST. The decreased platelet count was not associated with bleeding events.
The majority of the decreased platelets were transient and not below 75 × 109/l.

Liver enzymes
In the double-blinded treatment period, elevations in ALT or AST occurred in 27.9% and 18.3% of patients treated with satralizumab (monotherapy or in combination with IST) respectively, compared with 12.2% and 13.5% of patients receiving placebo or placebo plus IST. The majority of the elevations were below 3 x ULN, were transient and resolved without interruption of satralizumab.
Elevations in ALT or AST >3 x ULN occurred in 2.9% and 1.9% of patients treated with satralizumab (monotherapy or in combination with IST) respectively. These elevations were not associated with increases in total bilirubin.
Elevations of ALT above 5 x ULN were observed 4 weeks after initiation of therapy in one (1%) patient receiving satralizumab in combination with IST; normalising after discontinuation of treatment, and satralizumab was not reintroduced in this patient (see sections 4.2 and 4.4).

Lipid parameters

In the double-blinded treatment period, 10.6% of patients receiving satralizumab (monotherapy or in combination with IST) experienced elevations in total cholesterol above 7.75 mmol/l as compared with 1.4% of patients receiving placebo (or placebo plus IST); 20.2% of patients receiving satralizumab experienced elevations in triglycerides above 3.42 mmol/l as compared with 10.8% of patients receiving placebo.

Paediatric population

The safety and efficacy of satralizumab have been studied in 9 children ≥12 years of age. Frequency, type and severity of adverse reactions in children from 12 years of age are expected to be the same as in adults.

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 the form https://sideeffects.health.gov.il.