Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
The most frequently reported adverse reactions were upper respiratory infections.

Tabulated list of adverse reactions

Adverse reactions for risankizumab from clinical studies (Table 1) for psoriasis and psoriatic arthritis are listed by MedDRA system organ class and are 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 < 1/1,000); and very rare (< 1/10,000).

Table 1: List of adverse reactions

System Organ Class             Frequency                       Adverse reactions Infections and                 Very common                     Upper respiratory infestations                                                   infectionsa Common                          Tinea infectionsb
Uncommon                        Folliculitis
Nervous system                 Common                          Headachec disorders
Skin and subcutaneous          Common                          Pruritus tissue disorders                                               Rash
Uncommon                        Urticaria
General disorders and          Common                          Fatigued administration site                                            Injection site reactionse conditions a
Includes: respiratory tract infection (viral, bacterial, or unspecified), sinusitis (including acute), rhinitis, nasopharyngitis, pharyngitis (including viral), tonsillitis, laryngitis, tracheitis b
Includes: tinea pedis, tinea cruris, body tinea, tinea versicolor, tinea manuum, onychomycosis, fungal skin infection c
Includes: headache, tension headache, sinus headache d
Includes: fatigue, asthenia e
Includes: injection site bruising, erythema, haematoma, haemorrhage, irritation, pain, pruritus, reaction, swelling, induration, rash

Description of selected adverse reactions

Infections
The rate of infections was 75.5 events per 100 subject-years from the psoriasis clinical studies and 43.0 events per 100 subject-years from the psoriatic arthritis clinical studies, including long-term exposure to risankizumab. The majority of cases were non-serious and mild to moderate in severity and did not lead to discontinuation of risankizumab. The rate of serious infections was 1.7 events per 100 subject-years from the psoriasis studies and 2.6 events per 100 subject-years from the psoriatic arthritis studies (see section 4.4).

Psoriatic arthritis

Overall, the safety profile observed in patients with psoriatic arthritis treated with risankizumab was consistent with the safety profile observed in patients with plaque psoriasis.
Immunogenicity

As with all therapeutic proteins, there is the potential for immunogenicity with risankizumab. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.

For subjects treated with risankizumab at the recommended clinical dose for up to 52 weeks in psoriasis clinical trials, treatment-emergent anti-drug antibodies and neutralising antibodies were detected in 24% (263/1,079) and 14% (150/1,079) of evaluated subjects, respectively.

For most subjects with psoriasis, antibodies to risankizumab including neutralising antibodies were not associated with changes in clinical response or safety. Among the few subjects (approximately 1%; 7/1,000 at week 16 and 6/598 at week 52) with high antibody titres (>128), clinical response appeared to be reduced. The incidence of injection site reactions is numerically higher in the anti-drug antibody- positive groups compared with anti-drug antibody-negative groups over short-term (16 weeks: 2.7% vs 1.3%) and longer-term treatment (>52 weeks: 5.0% vs 3.3%). The injection site reactions were all mild to moderate in severity, none were serious, and none led to discontinuation of risankizumab.
For subjects treated with risankizumab at the recommended clinical dose for up to 28 weeks in psoriatic arthritis clinical trials, treatment-emergent anti-drug antibodies and neutralizing antibodies were detected in 12.1% (79/652) and 0% (0/652) of evaluated subjects, respectively. Antibodies to risankizumab were not associated with changes in clinical response or safety for psoriatic arthritis.

Elderly

There is limited safety information in subjects aged ≥65 years.
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