Jyseleca Adverse Reactions

Summary of the safety profile: Rheumatoid arthritis: The most frequently reported adverse reactions are nausea (3.5%), upper respiratory tract infection (URTI, 3.3%), urinary tract infection (UTI, 1.7%), dizziness (1.2%) and lymphopenia (1.0%).
Ulcerative colitis: In general, the overall safety profile observed in filgotinib-treated patients with ulcerative colitis was generally consistent with the safety profile observed in patients with rheumatoid arthritis.
Tabulated list of adverse reactions: The following adverse reactions are based on clinical studies (Table 10). The adverse reactions are listed below by system organ class and frequency. Frequencies are defined as follows: common (≥1/100 to <1/10 ) and uncommon (≥1/1,000 to <1/100). (See Table 10.)

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Laboratory changes: Creatinine: An increase in serum creatinine occurred with filgotinib treatment. At week 24 in the Phase 3 studies (FINCH 1, 2, and 3), the mean (SD) increase from baseline in serum creatinine was 0.07 (0.12) and 0.04 (0.11) mg/dL for filgotinib 200 mg and 100 mg, respectively. Mean creatinine values remained within the normal range.
Lipids: Treatment with filgotinib was associated with dose-dependent increases in total cholesterol and HDL levels, while LDL levels were slightly increased. LDL/HDL ratios were generally unchanged. Lipid changes were observed within the first 12 weeks of filgotinib treatment and remained stable thereafter.
Serum phosphate: Generally mild, transient or intermittent, and dose-dependent decreases in serum phosphate levels occurred during treatment with filgotinib and resolved without discontinuation of treatment. At week 24 in the Phase 3 studies (FINCH 1, 2, and 3), serum phosphate values of less than 2.2 mg/dL (the lower limit of normal) were reported in 5.3% and 3.8% of subjects receiving filgotinib 200 mg and 100 mg, respectively; no values below 1.0 mg/dL were reported.
In placebo-controlled Phase 3 studies with background DMARDs (FINCH 1 and FINCH 2) through 12 weeks, serum phosphate levels of less than 2.2 mg/dL were reported in 1.6%, 3.1%, and 2.4% in the placebo, filgotinib 200 mg, and filgotinib 100 mg groups, respectively.
Description of selected adverse reactions: Infections: Rheumatoid arthritis: In placebo-controlled studies with background DMARDs (FINCH 1, FINCH 2, DARWIN 1, and DARWIN 2), the frequency of infection over 12 weeks in the filgotinib 200 mg group was 18.1% compared to 13.3% in the placebo group. In the MTX controlled study FINCH 3, the frequency of infection over 24 weeks in the filgotinib 200 mg monotherapy and filgotinib 200 mg plus MTX groups was 25.2% and 23.1%, respectively, compared to 24.5% in the MTX group. The overall exposure-adjusted incidence rate (EAIR) of infections for the filgotinib 200 mg group across all seven Phase 2 and 3 clinical studies (2,267 patients) was 26.5 per 100 patient years of exposure (PYE).
In placebo-controlled studies with background DMARDs, the frequency of serious infection over 12 weeks in the filgotinib 200 mg group was 1.0% compared to 0.6% in the placebo group. In the MTX-controlled study FINCH 3, the frequency of serious infection over 24 weeks in the filgotinib 200 mg monotherapy and filgotinib 200 mg plus MTX groups was 1.4% and 1.0%, respectively, compared to 1.0% in the MTX group. The overall EAIR of serious infections for the filgotinib 200 mg group across all seven Phase 2 and 3 clinical studies (2,267 patients) was 1.7 per 100 PYE. The most common serious infection was pneumonia. The EAIR of serious infections remained stable with long term exposure.
In rheumatoid arthritis clinical studies, there was a higher incidence of serious infections in patients aged 65 years and older.
In placebo-controlled studies with background DMARDs, the frequencies of infectious ADRs over 12 weeks for filgotinib 200 mg compared to placebo were: URTI (3.3% versus 1.8%), UTI (1.7% versus 0.9%), pneumonia (0.6% versus 0.4%), and herpes zoster (0.1% versus 0.3%). Most of the herpes zoster events involved a single dermatome and were non-serious. The overall EAIR of herpes zoster across all seven Phase 2 and 3 clinical studies (2,267 and 1,647 total patients for 200 mg and 100 mg, respectively) was 1.6 and 1.1 per 100 PYE in the 200 mg group and 100 mg group, respectively.
Ulcerative colitis: The types of serious infections in the ulcerative colitis clinical studies were generally similar to those reported in the rheumatoid arthritis clinical studies with filgotinib monotherapy treatment groups.
Across the two placebo-controlled induction studies, the frequency of serious infections was 0.6% in the filgotinib 200 mg group, 1.1% in the filgotinib 100 mg group, and 1.1% in the placebo group. In the placebo-controlled maintenance study, the frequency of serious infections in the filgotinib 200 mg group was 1%, compared to 0% in the respective placebo group. In the maintenance study filgotinib 100 mg group, the frequency of serious infections was 1.7%, compared with 2.2% in the respective placebo group.
Opportunistic infections (excluding TB): In rheumatoid arthritis placebo-controlled studies with background DMARDs, there were no opportunistic infections over 12 weeks in the filgotinib 200 mg group or the placebo group. In the MTX-controlled study FINCH 3, the frequency of opportunistic infections over 24 weeks was 0, 0.2%, and 0 in the filgotinib 200 mg monotherapy, filgotinib 200 mg plus MTX, and MTX groups, respectively. The overall EAIR of opportunistic infections for the filgotinib 200 mg group across all seven Phase 2 and 3 rheumatoid arthritis clinical studies (2,267 patients) was 0.1 per 100 PYE.
Nausea: Nausea was generally transient and reported during the first 24 weeks of filgotinib treatment.
Creatine phosphokinase: Dose-dependent increases in creatine phosphokinase (CPK) occurred within the first 12 weeks of filgotinib treatment and remained stable thereafter. At week 24 in the Phase 3 studies (FINCH 1, 2, and 3), the mean (SD) increase from baseline in CPK was -16 (449), 61 (260), and 33 (80) U/L for placebo, filgotinib 200 mg and 100 mg, respectively.
In placebo-controlled Phase 3 studies with background DMARDs (FINCH 1 and FINCH 2) through 12 weeks, CPK elevations >5 × upper limit of normal (ULN) were reported in 0.5%, 0.3%, and 0.3% of patients in the placebo, filgotinib 200 mg, and filgotinib 100 mg groups, respectively. Most elevations >5 × ULN did not require treatment discontinuation.
Experience from long-term extension studies: Rheumatoid arthritis: In the long-term extension study DARWIN 3, patients enrolled from DARWIN 1 (N = 497) received filgotinib once a day for a median duration of 5.3 years and patients enrolled from DARWIN 2 (N = 242) received filgotinib once a day for a median duration of 5.6 years. In the long-term extension study FINCH 4, 1,530 patients received filgotinib 200 mg once daily and 1,199 patients received filgotinib 100 mg once daily for a median duration of 1.5 years. The safety profile of filgotinib was similar to that in the Phase 2 and Phase 3 studies.
Ulcerative colitis: In the long-term extension study (SELECTION LTE) in patients who participated in the SELECTION study, patients received filgotinib 200 mg (N = 871), filgotinib 100 mg (N = 157), or placebo (N = 133) for median durations of 55, 36, and 32 weeks, respectively. The safety profile of filgotinib was similar to that in the SELECTION induction and maintenance studies.
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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.