Adverse reactions : תופעות לוואי

8 ADVERSE REACTIONS

The following clinically significant adverse reactions are also discussed elsewhere in the labeling: 
•   Serious Infections [see Warnings and Precautions (7.1)]
•   Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions (7.2)] •   Malignancy [see Warnings and Precautions (7.3)]



8.1 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.

The safety of SAPHNELO was assessed through 52 weeks in patients with moderate to severe SLE who received anifrolumab 300 mg by intravenous infusion every 4 weeks (N=459), compared to placebo (N=466) in controlled clinical trials (Trials 1, 2 and 3) [see Clinical Studies (14)]. The population studied had a mean age of 41 years (range: 18 to 69), of which 93% were female, 60% White, 13% Black/African American, and 10%
Asian.

In the controlled-clinical trials, adverse reactions, irrespective of causality, were reported in 87% of patients receiving SAPHNELO and 79% of patients receiving placebo.

Adverse reactions that occurred at greater than or equal to 2% incidence are shown in Table 1.

Table 1 Adverse Reactions Occurring in ≥2% of Patients on SAPHNELO 300 mg (Trials 1, 2 and 3) at 52 weeks
Adverse Reaction                                     SAPHNELO                                            Placebo (N=459)                                            (N=466)
%                                                  %
Upper respiratory tract infection*                                  34                                               23 Bronchitis†                                                         11                                              5.2 Infusion-related reactions                                          9.4                                             7.1 Herpes Zoster                                                       6.1                                             1.3 Cough                                                               5.0                                             3.2 Respiratory tract infectionǂ                                        3.3                                             1.5 Hypersensitivity                                                    2.8                                             0.6 All patients received standard therapy
* Upper respiratory tract infections (including Upper respiratory tract infections, Nasopharyngitis, Pharyngitis) † Bronchitis (including Bronchitis, Bronchitis viral, Tracheobronchitis) ǂ Respiratory tract infection (including Respiratory tract infection, Respiratory tract infection viral, Respiratory tract infection bacterial) 
Long-term Safety

Patients who completed Trials 2 and 3 (Phase III feeder trials) were eligible to continue on treatment in a randomized, double-blind, placebo-controlled long-term extension (LTE) study, for an additional 3 years. The long-term safety of SAPHNELO was assessed in 257 patients who received anifrolumab 300 mg and 112 patients who received placebo in both a feeder trial and the LTE. Of these, 177 patients who received 


SAPHNELO (68.9%) and 52 patients who received placebo (46.4%) completed a total of 4 years on treatment.
The overall long-term safety profile of SAPHNELO was consistent with Trials 1, 2 and 3.


Specific Adverse Reactions

Infections
In the 52-week controlled-clinical trials, infections were reported in a greater proportion of patients while on treatment with SAPHNELO compared to placebo (69.7% [320/459] versus 55.4% [258/466]), corresponding to exposure-adjusted incidence rates (EAIR) of 141.8 and 99.9 per 100 patient years (PY), respectively.

Serious Infections

In the 52-week controlled-clinical trials, the incidence of serious infections while on treatment was 4.8% (22/459) in patients treated with SAPHNELO compared with 5.6% (26/466) in patients receiving placebo, corresponding to EAIR of 5.4 and 6.6 per 100 PY, respectively. The most frequent serious infection was pneumonia.

In the 52-week controlled-clinical trials, fatal infections occurred in 0.4% of patients receiving SAPHNELO and 0.2% of the patients receiving placebo.

During the LTE study, the most common serious infections were COVID-19 and pneumonia.

Herpes Zoster
In the 52-week controlled-clinical trials, the incidence of herpes zoster in patients while on treatment with SAPHNELO was 6.1% (28/459) and 1.3% (6/466) in patients on placebo, corresponding to EAIRs of 6.9 and 1.5 per 100 PY, respectively. Cases with multidermatomal involvement and disseminated presentation have been reported. Of the 28 SAPHNELO-treated patients with herpes zoster, 2 experienced disseminated disease requiring hospitalization compared to none among patients who received placebo.

Hypersensitivity Reactions Including Anaphylaxis

During the SLE development program, there was one report of an anaphylactic reaction in a patient who received 150 mg anifrolumab, and 4 reports of angioedema after 300 mg. In general, the hypersensitivity reactions were predominantly mild or moderate in intensity and did not lead to discontinuation of SAPHNELO.

In the 52-week controlled-clinical trials, hypersensitivity reactions occurred in 2.8% (13/459) of patients while on treatment with SAPHNELO and 0.6% (3/466) of patients on placebo, corresponding to EAIR of 3.2 and 0.7 per 100 PY, respectively. Serious hypersensitivity reactions were reported for 0.6% (3/459) of patients receiving SAPHNELO, including angioedema (n=2).

Infusion-related Reactions

Infusion-related reactions were mild to moderate in intensity; the most common symptoms were headache, nausea, vomiting, fatigue, and dizziness.

In the 52-week controlled-clinical trials, the incidence of infusion-related reactions while on treatment was 9.4% (43/459) in patients while on treatment with SAPHNELO and 7.1% (33/466) in patients on placebo, corresponding to EAIRs of 11.1 and 8.7 per 100 PY, respectively.

Malignancies

In 52-week controlled-clinical trials, malignancies (excluding non-melanoma skin cancers) were observed in 0.7% (3/459) and 0.6% (3/466) of patients receiving SAPHNELO and placebo, corresponding to EAIR of 0.7 and 0.7 per 100 PY, respectively. Malignant neoplasm (including non-melanoma skin cancers) was reported for 1.3% (6/459) patients receiving SAPHNELO, compared to 0.6% (3/466) patients receiving placebo (EAIR: 1.3 and 0.7 per 100 PY, respectively). The malignancies that were reported in more than one patient treated with SAPHNELO included breast cancer and squamous cell carcinoma.

8.2 Postmarketing Experience

The following adverse reaction has been identified during post-approval use of SAPHNELO. Because the 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.
Arthralgia.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization 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