Enspryng Adverse Reactions

Clinical Trials: Summary of the safety profile: The safety of Enspryng as monotherapy or in combination with IST was evaluated based on data from two phase III randomized, multicenter, double-blind, placebo-controlled clinical trials (BN40900 and BN40898), which include 63 patients exposed to Enspryng monotherapy and 41 patients exposed to Enspryng in combination with IST (see Pharmacology: Pharmacodynamics: Clinical/Efficacy Studies under Actions). In the double-blind controlled period, patient median exposure to satralizumab was approximately 2 years in both studies BN40900 and BN40898 each. The median exposure to placebo was approximately 1 year.
The most frequently reported adverse drug reactions (ADRs) were headache, arthralgia and injection related reactions.
Tabulated summary of adverse drug reactions from clinical trials: Table 9 summarizes the ADRs that have been reported in association with the use of Enspryng as monotherapy or in combination with IST in clinical trials. Patients in the Enspryng groups in both clinical studies had longer treatment period than those in the placebo (or placebo in combination with IST) groups, ADRs were evaluated during 194 patient-years (PY) in the Enspryng groups and 100 PY in the placebo groups. ADRs from clinical trials (Table 9) are listed by MedDRA system organ class. The corresponding frequency category for each adverse drug reaction is based on 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 <1/1000), very rare (<1/10,000). (See Table 9.)

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Description of selected adverse drug reactions from clinical trials: Injection-Related Reactions (IRRs): IRRs reported in patients treated with Enspryng as monotherapy or in combination with IST were predominantly mild to moderate, most occurred within 24 hours after injection. The most commonly reported systemic symptoms were diarrhea and headache. The most commonly reported local injection site reactions were flushing, erythema, pruritus, rash and pain. None of the injection related reactions required dose interruption or discontinuation.
Infections: In the Enspryng monotherapy study, the rate of infections was lower in patients treated with Enspryng [99.8 events/100 PY (95% CI: 82.4, 119.8)] compared with patients receiving placebo [162.6 events/100 PY (95% CI: 125.8, 206.9)]. The rate of serious infections was 5.2 events/100 PY (95% CI: 1.9, 11.3) in patients treated with Enspryng compared with 9.9 events/100 PY (95% CI: 2.7, 25.2) in patients receiving placebo.
In patients treated with Enspryng in combination with IST, the rate of infections was 132.5 events/100 PY (95% CI: 108.2, 160.5) compared with 149.6 events/100 PY (95% CI: 120.1, 184.1) in patients receiving placebo in combination with IST; the rate of serious infections was 2.6 events/100 PY (95% CI: 0.3, 9.2) compared with 5.0 events/100 PY (95% CI: 1.0, 14.7) in patients receiving placebo in combination with IST.
Body weight increase: In the double-blinded treatment period, body weight increase ≥ 15% from baseline were observed in 3.8% of patients treated with Enspryng (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 Enspryng (monotherapy or in combination with IST) as compared with 21.6% of patients receiving placebo (or plus IST). The majority of neutrophil decreases were transient or intermittent.
Of the patients in the Enspryng group, 9.6% had neutrophils below 1 x 10⁹/L as compared with 5.4% in placebo or placebo plus IST, which was not temporally associated with any serious infections.
Platelets: In the double-blinded treatment period, decreases in platelet counts occurred in 24.0% of patients on Enspryng (monotherapy or in combination with IST) as compared with 9.5% of patients receiving placebo or placebo plus IST. The decreased platelet counts were not associated with bleeding events.
The majority of the decreased platelets were transient and not below 75 × 10⁹/L. None of the patients had a decrease in platelet count to ≤50 × 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 Enspryng (monotherapy or as 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 3x ULN, were transient, and resolved without interruption of Enspryng.
Elevations in ALT or AST >3x ULN occurred in 2.9% and 1.9% of patients treated with Enspryng (monotherapy or in combination with IST) respectively, which were not associated with increases in total bilirubin. Elevations of ALT above 5x ULN were observed 4 weeks after initiation of therapy in one patient receiving Enspryng in combination with IST, normalizing after discontinuation of Enspryng.
Lipid parameters: In the double-blinded treatment period, 10.6% of patients receiving Enspryng (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 plus IST; 20.2% of patients receiving Enspryng experienced elevations in triglycerides above 3.42 mmol/L as compared with 10.8% of patients receiving placebo. The elevations in lipid parameters did not require dose interruption.
Postmarketing Experience: Not applicable.