Skyrizi

150 mg: The solution is colourless to yellow and clear to slightly opalescent.
Each pre-filled pen contains 150 mg risankizumab in 1 mL solution.
360 mg: The solution is colourless to yellow and clear to slightly opalescent.
Each cartridge contains 360 mg of risankizumab in 2.4 mL solution.
Excipients with known effect: This medicinal product contains 0.48 mg of polysorbate 20 in each 360 mg dose.
600 mg: The solution is colourless to slightly yellow and clear to slightly opalescent.
Each vial contains 600 mg of risankizumab in 10.0 mL of solution.
Excipients with known effect: This medicinal product contains 2 mg of polysorbate 20 in each 600 mg dose.
Risankizumab is a humanised immunoglobulin G1 (IgG1) monoclonal antibody selective to the interleukin (IL)-23 protein produced in Chinese Hamster Ovary cells using recombinant DNA technology.
Excipients/Inactive Ingredients: Sodium acetate trihydrate, Acetic acid, Trehalose dihydrate, Polysorbate 20, Water for injections.

Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors. ATC code: L04AC18.
Pharmacology: Pharmacodynamics: Mechanism of action: Risankizumab is a humanised immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds with high affinity to the p19 subunit of human interleukin 23 (IL-23) cytokine without binding to IL-12 and inhibits its interaction with the IL-23 receptor complex. IL-23 is a cytokine that is involved in inflammatory and immune responses. By blocking IL-23 from binding to its receptor, risankizumab inhibits IL-23-dependent cell signalling and release of proinflammatory cytokines.
150 mg: Pharmacodynamic effects: In a study of subjects with psoriasis, expression of genes associated with the IL-23/IL-17 axis was decreased in the skin after single doses of risankizumab. Reductions in epidermal thickness, infiltration of inflammatory cells, and expression of psoriatic disease markers were also observed in psoriatic lesions.
In a study of subjects with psoriatic arthritis, statistically significant and clinically meaningful reduction from baseline was observed at week 24 in IL-23 and IL-17-associated biomarkers, including serum IL-17A, IL-17F, and IL-22 following treatment with risankizumab 150 mg subcutaneously at week 0, week 4, and every 12 weeks thereafter.
Clinical efficacy and safety: Plaque Psoriasis: The efficacy and safety of risankizumab was assessed in 2 109 subjects with moderate to severe plaque psoriasis in four multicentre, randomised, double-blind studies (ULTIMMA-1, ULTIMMA-2, IMMHANCE, and IMMVENT). Enrolled subjects were 18 years of age and older with plaque psoriasis who had a body surface area (BSA) involvement of ≥10%, a static Physician Global Assessment (sPGA) score of ≥3 in the overall assessment (plaque thickness/induration, erythema, and scaling) of psoriasis on a severity scale of 0 to 4, a Psoriasis Area and Severity Index (PASI) score ≥12, and who were candidates for systemic therapy or phototherapy.
Overall, subjects had a median baseline PASI score of 17.8, a median BSA of 20.0%, and a median baseline DLQI score of 13.0. Baseline sPGA score was severe in 19.3% of subjects and moderate in 80.7% of subjects. A total of 9.8% of study subjects had a history of diagnosed psoriatic arthritis.
Across all studies, 30.9% of subjects were naïve to any systemic therapy (including non-biologic and biologic), 38.1% had received prior phototherapy or photochemotherapy, 48.3% had received prior non-biologic systemic therapy, 42.1% had received prior biologic therapy, and 23.7% had received at least one anti-TNF alpha agent for the treatment of psoriasis.
ULTIMMA-1 and ULTIMMA-2: ULTIMMA-1 and ULTIMMA-2 enrolled 997 subjects (598 randomised to risankizumab 150 mg, 199 to ustekinumab 45 mg or 90 mg [according to baseline weight], and 200 to placebo). Subjects received treatment at week 0, week 4, and every 12 weeks thereafter. The two co-primary endpoints in ULTIMMA-1 and ULTIMMA-2 were the proportion of subjects who achieved 1) PASI 90 response and 2) sPGA score of clear or almost clear (sPGA 0 or 1) at week 16 versus placebo. The results for the co-primary and other endpoints are presented in Table 1 and Figure 1. (See Table 1 and Figure 1.)

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Examination of age, gender, race, body weight ≤130 kg, baseline PASI score, concurrent psoriatic arthritis, previous non-biologic systemic treatment, previous biologic treatment, and previous failure of a biologic did not identify differences in response to risankizumab among these subgroups.
Improvements were observed in psoriasis involving the scalp, the nails, and the palms and soles at week 16 and week 52 in subjects treated with risankizumab. (See Table 2.)

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Anxiety and depression, as measured by the Hospital Anxiety and Depression Scale (HADS), improved in the risankizumab group at week 16 compared with the placebo group.
Maintenance of response: In an integrated analysis of subjects receiving risankizumab in ULTIMMA-1 and ULTIMMA-2 for PASI 100 responders at week 16, 79.8% (206/258) of the subjects who continued on risankizumab maintained the response at week 52. For PASI 90 responders at week 16, 88.4% (398/450) of subjects maintained the response at week 52.
The safety profile of risankizumab with up to 77 weeks of exposure was consistent with the profile observed up to 16 weeks.
IMMHANCE: IMMHANCE enrolled 507 subjects (407 randomised to risankizumab 150 mg and 100 to placebo). Subjects received treatment at week 0, week 4, and every 12 weeks thereafter. Subjects who were originally on risankizumab and had a sPGA response of clear or almost clear at week 28 were re-randomised to continue risankizumab every 12 weeks through week 88 (with follow-up 16 weeks after last risankizumab dose) or have treatment withdrawn.
At week 16, risankizumab was superior to placebo on the co-primary endpoints of sPGA of clear or almost clear (83.5% risankizumab vs 7.0% placebo) and PASI 90 (73.2% risankizumab vs 2.0% placebo).
Of the 31 subjects from the IMMHANCE study with latent tuberculosis (TB) who did not receive prophylaxis during the study, none developed active TB during the mean follow-up of 55 weeks on risankizumab.
Among subjects with sPGA of clear or almost clear at week 28 in IMMHANCE, 81.1% (90/111) of subjects re-randomised to continued treatment with risankizumab maintained this response at week 104 compared with 7.1% (16/225) who were re-randomised to withdrawal from risankizumab. Of these subjects, 63.1% (70/111) of subjects re-randomised to continued treatment with risankizumab achieved a sPGA clear response at week 104 compared with 2.2% (5/225) who were re-randomised to withdrawal from risankizumab.
Among subjects who achieved sPGA of clear or almost clear at week 28 and relapsed to sPGA of moderate or severe following withdrawal from risankizumab, 83.7% (128/153) regained sPGA of clear or almost clear after 16 weeks of retreatment. Loss of sPGA of clear or almost clear was observed as early as 12 weeks after a missed dose. Of those subjects who were re-randomised to withdraw from treatment, 80.9% (182/225) relapsed, and the median time to relapse was 295 days. No characteristics were identified to predict the time to loss of response or likelihood of regaining response at the individual patient level.
IMMVENT: IMMVENT enrolled 605 subjects (301 randomised to risankizumab and 304 to adalimumab). Subjects randomised to risankizumab received 150 mg of treatment at week 0, week 4, and every 12 weeks thereafter. Subjects randomised to adalimumab received 80 mg at week 0, 40 mg at week 1, and 40 mg every other week through week 15. Starting at week 16, subjects who were receiving adalimumab continued or switched treatment based on response: <PASI 50 were switched to risankizumab; PASI 50 to <PASI 90 were re-randomised to either continue adalimumab or switch to risankizumab; PASI 90 continued to receive adalimumab.
Results are presented in Table 3. (See Table 3.)

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For subjects who had PASI 50 to <PASI 90 with adalimumab at week 16 and were re-randomised, differences in PASI 90 response rates between switching to risankizumab and continuing adalimumab were noted 4 weeks after re-randomisation (49.1% vs 26.8%, respectively).
Results 28 weeks after re-randomisation are presented in Table 4 and Figure 2. (See Table 4 and Figure 2.)

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In 270 subjects who switched from adalimumab to risankizumab without a washout period, the safety profile of risankizumab was similar to that in subjects who initiated risankizumab after washout of any prior systemic therapies.
Psoriatic arthritis: Risankizumab has been shown to improve signs and symptoms, physical function, health-related quality of life, and the proportion of subjects with no radiographic progression in adults with active psoriatic arthritis (PsA).
The safety and efficacy of risankizumab were assessed in 1 407 subjects with active PsA in 2 randomised, double-blind, placebo-controlled studies (964 in KEEPSAKE1 and 443 in KEEPSAKE2).
Subjects in these studies had a diagnosis of PsA for at least 6 months based on the Classification Criteria for Psoriatic Arthritis (CASPAR), a median duration of PsA of 4.9 years at baseline, ≥5 tender joints and ≥5 swollen joints, and active plaque psoriasis or nail psoriasis at baseline. 55.9% of subjects had ≥3% BSA with active plaque psoriasis. 63.4% and 27.9% of subjects had enthesitis and dactylitis, respectively. In KEEPSAKE1, where nail psoriasis was further assessed, 67.3% had nail psoriasis.
In both studies, subjects were randomised to receive risankizumab 150 mg or placebo at weeks 0, 4, and 16. Starting from week 28, all subjects received risankizumab every 12 weeks.
In KEEPSAKE1, all subjects had a previous inadequate response or intolerance to non-biologic DMARD therapy and were biologic naïve. In KEEPSAKE2, 53.5% of subjects had a previous inadequate response or intolerance to non-biologic DMARD therapy and 46.5% of subjects had a previous inadequate response or intolerance to biologic therapy.
In both studies, 59.6% of subjects were receiving concomitant methotrexate (MTX), 11.6% were receiving concomitant non-biologic DMARDs other than MTX, and 28.9% were receiving risankizumab monotherapy.
Clinical Response: Treatment with risankizumab resulted in significant improvement in measures of disease activity compared with placebo at week 24. For both studies, the primary endpoint was the proportion of subjects who achieved an American College of Rheumatology (ACR) 20 response at week 24. The key efficacy results are shown in Table 5. (See Table 5.)

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Response over time: In KEEPSAKE1, a greater ACR20 response was observed in the risankizumab group compared to placebo as early as week 4 (25.7%) and the treatment difference continued over time to week 24 (see Figure 3).

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A greater ACR20 response for risankizumab versus placebo was seen as early as week 4 in 19.6% of subjects in KEEPSAKE2.
Responses observed in risankizumab groups were similar regardless of concomitant non-biologic DMARD use, number of prior non-biologic DMARDs, age, gender, race, and BMI. In KEEPSAKE2, responses were seen regardless of prior biologic therapy.
The safety profile of risankizumab with up to 52 weeks of exposure was consistent with the profile observed up to 24 weeks.
In both studies, the proportion of subjects achieving modified PsA Response Criteria (PsARC) at week 24 was higher in subjects receiving risankizumab compared with placebo. In addition, subjects receiving risankizumab achieved greater improvement in Disease Activity Score (28 joints) using CRP (DAS28-CRP) compared with placebo at week 24. Improvements were maintained through week 52 for PsARC and DAS28-CRP.
Treatment with risankizumab resulted in improvements in individual ACR components, Health Assessment Questionnaire-Disability Index (HAQ-DI), pain assessment, and high-sensitivity C-reactive protein (hsCRP) compared with placebo.
Treatment with risankizumab resulted in statistically significant improvement in the skin manifestations of psoriasis in subjects with PsA.
Treatment with risankizumab resulted in statistically significant improvement in the modified Nail Psoriasis Severity Index (mNAPSI) and the 5-point Physician's Global Assessment of Fingernail Psoriasis (PGA-F) scores in subjects with nail psoriasis at baseline (67.3%) in KEEPSAKE1. This improvement was maintained through week 52 (see Table 6).

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Radiographic Response: In KEEPSAKE1, inhibition of progression of structural damage was assessed radiographically and expressed as the change in modified Total Sharp Score (mTSS) at week 24, compared with baseline. The mTSS score was modified for PsA by addition of hand distal interphalangeal (DIP) joints. At week 24, the mean progression of structural damage with risankizumab (mean mTSS 0.23) compared with placebo (mean mTSS 0.32) was not statistically significant. At week 24, the proportion of subjects with no radiographic progression (defined as a change from baseline in mTSS ≤0) was higher with risankizumab (92.4%) compared with placebo (87.7%). This response was maintained through week 52.
Physical Function and Health Related Quality of Life: In both studies, subjects treated with risankizumab showed statistically significant improvement from baseline in physical function as assessed by HAQ-DI at week 24 (KEEPSAKE1 (-0.31) compared with placebo (-0.11) (p ≤0.001)), (KEEPSAKE2 (-0.22) compared with placebo (-0.05) (p ≤0.001)). At week 24, a greater proportion of subjects achieved a clinically meaningful reduction of at least 0.35 in HAQ-DI score from baseline in the risankizumab group compared with placebo. Improvements in physical function were maintained through week 52.
In both studies, subjects treated with risankizumab demonstrated significant improvements in the SF-36 V2 physical component summary scores and in FACIT-Fatigue scores at week 24, compared with placebo, with improvements maintained through week 52.
At baseline, psoriatic spondylitis was reported in 19.6% (7.9% diagnosed by radiograph or MRI) of subjects in KEEPSAKE1 and 19.6% (5% diagnosed by radiograph or MRI) of subjects in KEEPSAKE2. Subjects with clinically assessed psoriatic spondylitis who were treated with risankizumab showed improvements from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores compared with placebo at week 24. Improvements were maintained through week 52. There is insufficient evidence of the efficacy of risankizumab in subjects with radiograph- or MRI-confirmed ankylosing spondylitis-like psoriatic arthropathy due to the small number of subjects studied.
360 mg/600 mg: Pharmacodynamic effects: In a study of subjects with psoriasis, expression of genes associated with the IL-23/IL-17 axis was decreased in the skin after single doses of risankizumab. Reductions in epidermal thickness, infiltration of inflammatory cells, and expression of psoriatic disease markers were also observed in psoriatic lesions.
In a Phase 2 study of subjects with Crohn's disease, expression of genes associated with the IL-23/Th17 axis were decreased in gut tissue after multiple doses of risankizumab. Reductions in faecal calprotectin (FCP), serum C reactive protein (CRP) and IL-22 were also observed after multiple doses in Phase 3 induction studies in Crohn's patients. Decreases in FCP, CRP and serum IL-22 were maintained out to week 52 of the maintenance study.
Clinical efficacy and safety: Crohn's disease: The efficacy and safety of risankizumab were assessed in 1 419 subjects with moderately to severely active Crohn's disease in three multicentre, randomised, double-blind, placebo-controlled clinical studies. Enrolled subjects were 16 years of age or older with a Crohn's Disease Activity Index (CDAI) of 220 to 450, an average daily stool frequency (SF) ≥4 and/or average daily abdominal pain score (APS) ≥2, and a Simple Endoscopic Score for CD (SES-CD) of ≥6, or ≥4 for isolated ileal disease, excluding the narrowing component and confirmed by a central reviewer.
There were two 12-week intravenous induction studies (ADVANCE and MOTIVATE), which included a 12-week extension period for subjects who did not achieve SF/APS clinical response (≥30% decrease in SF and/or ≥30% decrease in APS and both not worse than baseline) at week 12. ADVANCE and MOTIVATE were followed by a 52-week randomised withdrawal study of subcutaneous maintenance treatment (FORTIFY) that enrolled subjects with SF/APS clinical response to intravenous induction treatment, representing at least 64 weeks of therapy.
ADVANCE and MOTIVATE: In studies ADVANCE and MOTIVATE, subjects were randomised to receive risankizumab at either 600 mg (recommended dose), 1 200 mg, or placebo, at week 0, week 4, and week 8.
In ADVANCE, 58% (491/850) subjects had failed or were intolerant to treatment with one or more biologic therapies (prior biologic failure), and 42% (359/850) had failed or were intolerant to therapy with conventional therapies but not biologic therapies (without prior biologic failure). In ADVANCE, among the subjects without prior biologic failure, (87%) 314/359 were naïve to biologic therapy and the remaining 13% had received a biologic but never failed or demonstrated intolerance. All patients in MOTIVATE had prior biologic failure.
In both studies, a greater proportion of subjects treated with risankizumab achieved the co-primary endpoints of clinical remission at week 12 and endoscopic response at week 12 compared to placebo. Enhanced SF/APS clinical response and clinical remission were significant as early as week 4 in subjects treated with risankizumab and continued to improve through week 12 (see Table 7).

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At week 12, a higher proportion of subjects treated with risankizumab achieved a decrease of at least 100 points in baseline CDAI compared to placebo (ADVANCE, risankizumab =60%, placebo=37%, p<0.001; MOTIVATE, risankizumab =60%, placebo=30%, p<0.001).
At week 12, a higher proportion of subjects treated with risankizumab achieved both enhanced SF/APS clinical response and endoscopic response at week 12 compared to placebo (ADVANCE, risankizumab =31%, placebo=8%, p<0.001; MOTIVATE, risankizumab =21%, placebo=7%, p<0.001).
The results for the co-primary endpoints for the subgroups (without allowing for multiplicity) of subjects with and without prior biologic failure are presented in Table 8. (See Table 8.)

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In ADVANCE, a higher proportion of subjects treated with risankizumab with and without prior biologic failure achieved CDAI<150 compared to placebo (With prior biologic failure, risankizumab =42%, placebo=26%; Without prior biologic failure, risankizumab =49%, placebo=23%).
CD-related hospitalisations: Rates of CD-related hospitalisations through week 12 were lower in subjects treated with risankizumab compared to placebo (ADVANCE, risankizumab =3%, placebo=12%, p<0.001; MOTIVATE, risankizumab =3%, placebo=11%, p≤0.01).
FORTIFY: The maintenance study FORTIFY evaluated 462 subjects with SF/APS clinical response to 12 weeks of risankizumab intravenous induction treatment in studies ADVANCE and MOTIVATE. Subjects were randomised to continue to receive a maintenance regimen of risankizumab 360 mg subcutaneously (recommended dose), or risankizumab 180 mg subcutaneously every 8 weeks, or to withdraw from risankizumab induction and receive placebo subcutaneously every 8 weeks for up to 52 weeks.
The co-primary endpoints were clinical remission at week 52 and, endoscopic response at week 52. Co-primary endpoints were also measured in subjects with and without prior biologic failure (see Table 9).

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Deep remission (clinical remission and endoscopic remission) at week 52 was observed at higher rates in subjects treated with risankizumab intravenously/risankizumab subcutaneously compared to subjects who received risankizumab intravenously/placebo subcutaneously (28% vs. 10%, respectively, nominal p<0.001).
At week 52, a higher proportion of subjects treated with risankizumab intravenously/risankizumab subcutaneously achieved CDAI <150 compared to risankizumab intravenously/placebo subcutaneously (52% vs. 41%, respectively, nominal p≤0.01). A higher proportion of subjects treated with risankizumab intravenously/risankizumab subcutaneously achieved a decrease of at least 100 points in baseline CDAI score compared to subjects treated with risankizumab intravenously/placebo subcutaneously (62% vs. 48%, respectively, nominal p≤0.01).
91 subjects who did not demonstrate SF/APS clinical response 12 weeks after risankizumab induction in studies ADVANCE and MOTIVATE received subcutaneous 360 mg dose of risankizumab at week 12 and week 20. Of these subjects, 64% (58/91) achieved SF/APS clinical response at week 24; 33 of the subjects achieving SF/APS clinical response enrolled in FORTIFY and continued receiving risankizumab 360 mg subcutaneously every 8 weeks for up to 52 weeks. Among these subjects, 55% (18/33) achieved clinical remission and 45% (15/33) achieved endoscopic response at week 52.
During FORTIFY, 30 subjects had loss of response to risankizumab 360 mg subcutaneously treatment and received rescue treatment with risankizumab (1 200 mg intravenous single dose, followed by 360 mg subcutaneously every 8 weeks). Of these subjects, 57% (17/30) achieved SF/APS clinical response at week 52. In addition, 20% (6/30) and 34% (10/29) of subjects achieved clinical remission and endoscopic response at week 52, respectively.
Health-related and quality of life outcomes: Health-related quality of life was assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ) and 36-Item Short Form Health Survey (SF-36). Improvement in fatigue was evaluated by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale. Work productivity was assessed by the Work Productivity and Activity Impairment CD (WPAI-CD) Questionnaire.
At week 12 of ADVANCE and MOTIVATE, subjects treated with risankizumab achieved clinically meaningful improvements from baseline in IBDQ total score, all IBDQ domain scores (bowel symptoms, systemic function, emotional function, and social function), SF-36 Physical and Mental Component Summary Score, FACIT-Fatigue and WPAI-CD compared to placebo. For WPAI-CD greater reductions in impairment while working, overall work impairment, and activity impairment were demonstrated in ADVANCE; and greater reduction in activity impairment was demonstrated in MOTIVATE. These improvements were maintained in subjects treated with risankizumab intravenously/risankizumab subcutaneously in FORTIFY through week 52.
Pharmacokinetics: 150 mg: The pharmacokinetics of risankizumab was similar between subjects with plaque psoriasis and subjects with psoriatic arthritis.
360 mg/600 mg: The pharmacokinetics of risankizumab was similar between plaque psoriasis, psoriatic arthritis, and Crohn's disease.
Absorption: Risankizumab exhibited linear pharmacokinetics with dose-proportional increase in exposure across dose ranges of: 150 mg: 18 to 300 mg and 0.25 to 1 mg/kg administered subcutaneously, and 200 to 1 200 mg and 0.01 to 5 mg/kg administered intravenously; 360 mg/600 mg: 18 to 360 mg and 0.25 to 1 mg/kg administered subcutaneously, and 200 to 1 800 mg and 0.01 to 5 mg/kg administered intravenously.
Following subcutaneous dosing of risankizumab, peak plasma concentrations were achieved between 3-14 days after dosing with an estimated absolute bioavailability of 74-89%. With dosing of 150 mg at week 0, week 4, and every 12 weeks thereafter, estimated steady-state peak and trough plasma concentrations are 12 and 2 μg/mL, respectively.
Bioequivalence was demonstrated between a single risankizumab 150 mg injection and two risankizumab 75 mg injections in pre-filled syringe. Bioequivalence was also demonstrated between risankizumab 150 mg pre-filled syringe and pre-filled pen.
In subjects with Crohn's disease treated with 600 mg intravenous induction dose at weeks 0, 4, and 8 followed by 360 mg subcutaneous maintenance dose at week 12 and every 8 weeks thereafter, maximum median peak and trough concentrations are estimated to be 156 and 38.8 µg/mL respectively during the induction period (weeks 8-12) and steady-state median peak and trough concentrations are estimated to be 28.0 and 8.13 µg/mL respectively during the maintenance period (weeks 40-48) (360 mg & 600 mg only).
Distribution: The mean (±standard deviation) steady-state volume of distribution (V_ss) of risankizumab was 11.4 (±2.7) L in Phase 3 studies in subjects with psoriasis, indicating that the distribution of risankizumab is primarily confined to the vascular and interstitial spaces. In a typical 70 kg subject with Crohn's disease, V_ss was 7.68 L.
Biotransformation: Therapeutic IgG monoclonal antibodies are typically degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgGs. Risankizumab is not expected to be metabolised by cytochrome P450 enzymes.
Elimination: The mean (±standard deviation) systemic clearance (CL) of risankizumab was 0.3 (±0.1) L/day in Phase 3 studies in subjects with psoriasis. The mean terminal elimination half-life of risankizumab ranged from 28 to 29 days in Phase 3 studies in subjects with psoriasis. For a typical 70 kg subject with Crohn's disease, CL was 0.30 L/day and terminal elimination half-life was 21 days.
As an IgG1 monoclonal antibody, risankizumab is not expected to be filtered by glomerular filtration in the kidneys or to be excreted as an intact molecule in the urine.
Linearity/non-linearity: Risankizumab exhibited linear pharmacokinetics with approximately dose-proportional increases in systemic exposure (C_max and AUC) in the evaluated dose ranges of: 150 mg: 18 to 300 mg or 0.25 to 1 mg/kg subcutaneous administration in healthy subjects or subjects with psoriasis; 360 mg/600 mg: 18 to 360 mg or 0.25 to 1 mg/kg subcutaneous administration and 200 to 1800 mg and 0.01 to 5 mg/kg administered intravenously in healthy subjects or subjects with psoriasis or Crohn's disease.
Interactions: Interaction studies were conducted in subjects with plaque psoriasis, or Crohn's disease to assess the effect of repeated administration of risankizumab on the pharmacokinetics of cytochrome P450 (CYP) sensitive probe substrates. The exposure of caffeine (CYP1A2 substrate), warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), metoprolol (CYP2D6 substrate) and midazolam (CYP3A substrate) following risankizumab treatment were comparable to their exposures prior to risankizumab treatment, indicating no clinically meaningful interactions through these enzymes.
Population pharmacokinetic analyses indicated that risankizumab exposure was not impacted by concomitant medicinal products used by some subjects with plaque psoriasis or psoriatic arthritis during the clinical studies. Similar lack of impact by concomitant medicinal products was observed based on population pharmacokinetic analyses in Crohn's disease.
Special populations: Paediatric population: The pharmacokinetics of risankizumab in paediatric subjects under 16 years of age has not been established. Of the 1 574 subjects with Crohn's disease exposed to risankizumab, 12 were 16 to 17 years old. Risankizumab exposures in 16 to 17 year-old subjects with Crohn's disease were similar to those in adults. Age was not found to have any significant impact on risankizumab exposures based on the population pharmacokinetic analyses.
Elderly: No overall differences in risankizumab exposure were observed between older and younger subjects who received risankizumab.
150 mg: Of the 2 234 subjects with plaque psoriasis exposed to risankizumab, 243 were 65 years or older and 24 subjects were 75 years or older. Of the 1 542 subjects with psoriatic arthritis exposed to risankizumab, 246 were 65 years or older and 34 subjects were 75 years or older.
360 mg/600 mg: Of the 2 234 subjects with plaque psoriasis exposed to risankizumab, 243 were 65 years or older and 24 subjects were 75 years or older. Of the 1 574 subjects with Crohn's disease exposed to risankizumab, 72 were 65 years or older and 5 subjects were 75 years or older.
Patients with renal or hepatic impairment: No specific studies have been conducted to determine the effect of renal or hepatic impairment on the pharmacokinetics of risankizumab. Based on population pharmacokinetic analyses, serum creatinine levels, creatinine clearance, or hepatic function markers (ALT/AST/bilirubin) did not have a meaningful impact on risankizumab clearance in subjects with plaque psoriasis, psoriatic arthritis or Crohn's disease.
As an IgG1 monoclonal antibody, risankizumab is mainly eliminated via intracellular catabolism and is not expected to undergo metabolism via hepatic cytochrome P450 enzymes or renal elimination.
Body weight: Risankizumab clearance and volume of distribution increase as body weight increases which may result in reduced efficacy in subjects with high body weight (>130 kg). However, this observation is based on a limited number of subjects with plaque psoriasis. Body weight had no clinically meaningful impact on risankizumab exposure or efficacy in psoriatic arthritis, or Crohn's disease. No dose adjustment based on body weight is currently recommended.
Gender or race: The clearance of risankizumab was not significantly influenced by gender or race in adult subjects with plaque psoriasis, psoriatic arthritis or Crohn's disease. No clinically meaningful differences in risankizumab exposure were observed in Chinese or Japanese subjects compared to Caucasian subjects in clinical pharmacokinetic studies in healthy volunteers.
Toxicology: Preclinical safety data: 150 mg: Nonclinical data revealed no special hazard for humans based on repeat-dose toxicity studies including safety pharmacology evaluations, and a reproductive and developmental toxicity study in cynomolgus monkeys at doses of up to 50 mg/kg/week (producing exposures of about 70 times the clinical exposure at maximum recommended human dose [MRHD]).
Mutagenicity and carcinogenicity studies have not been conducted with risankizumab. In a 26-week chronic toxicology study in cynomolgus monkeys at doses of up to 50 mg/kg/week (about 70 times the clinical exposure at the MRHD), there were no pre-neoplastic or neoplastic lesions observed and no adverse immunotoxicity or cardiovascular effects were noted.
360 mg/600 mg: Nonclinical data revealed no special hazard for humans based on repeat-dose toxicity studies including safety pharmacology evaluations and an enhanced pre- and post- natal developmental toxicity study in cynomolgus monkeys at doses of up to 50 mg/kg/week, producing exposures 10 times the clinical exposures during induction at a dose of 600 mg intravenous every 4 weeks and 39 times the clinical exposures for maintenance when given 360 mg subcutaneously every 8 weeks for Crohn's disease.
Mutagenicity and carcinogenicity studies have not been conducted with risankizumab. In a 26-week chronic toxicology study in cynomolgus monkeys at doses of up to 50 mg/kg/week (7 times the clinical exposures during induction at a dose of 600 mg intravenous every 4 weeks and 28 times the clinical exposures for maintenance when given 360 mg subcutaneously every 8 weeks for Crohn's disease), there were no pre-neoplastic or neoplastic lesions observed and no adverse immunotoxicity or cardiovascular effects were noted.

150 mg: Plaque Psoriasis: Skyrizi is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy.
Psoriatic Arthritis: Skyrizi, alone or in combination with methotrexate (MTX), is indicated for the treatment of active psoriatic arthritis in adults who have had an inadequate response or who have been intolerant to one or more disease-modifying antirheumatic drugs (DMARDs).
360 mg/600 mg: Skyrizi is indicated for the treatment of adult patients with moderately to severely active Crohn's disease who have had an inadequate response to, lost response to, or were intolerant to conventional therapy or a biologic therapy.

Skyrizi is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of conditions for which Skyrizi is indicated.
Posology: 150 mg: The recommended dose is 150 mg administered as a subcutaneous injection at week 0, week 4, and every 12 weeks thereafter.
Consideration should be given to discontinuing treatment in patients who have shown no response after 16 weeks of treatment. Some plaque psoriasis patients with initial partial response may subsequently improve with continued treatment beyond 16 weeks.
360 mg/600 mg: The recommended dose is 600 mg administered by intravenous infusion at week 0, week 4, and week 8, followed by 360 mg administered by subcutaneous injection at week 12, and every 8 weeks thereafter. Consideration should be given to discontinuing treatment in patients who have shown no evidence of therapeutic benefit by week 24.
Missed dose: If a dose is missed, the dose should be administered as soon as possible. Thereafter, dosing should be resumed at the regular scheduled time.
Special populations: Elderly (aged 65 years and over): No dose adjustment is required (see Pharmacology: Pharmacokinetics under Actions).
There is limited information in subjects aged ≥65 years.
Renal or hepatic impairment: No specific studies were conducted to assess the effect of hepatic or renal impairment on the pharmacokinetics of risankizumab. These conditions are generally not expected to have any significant impact on the pharmacokinetics of monoclonal antibodies and no dose adjustments are considered necessary (see Pharmacology: Pharmacokinetics under Actions).
Paediatric population: 150 mg: The safety and efficacy of risankizumab in children and adolescents aged 5 to 18 years have not been established. No data are available.
There is no relevant use of risankizumab in children aged below 6 years for the indication of moderate to severe plaque psoriasis or in children aged below 5 years for the indication of psoriatic arthritis.
360 mg/600 mg: The safety and efficacy of Skyrizi in children aged 0-17 years for the treatment of Crohn's disease have not yet been established. Currently available data are described in Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions but no recommendation on posology can be made.
Overweight patients: No dose adjustment is required (see Pharmacology: Pharmacokinetics under Actions).
Method of administration: 150 mg/360 mg: Skyrizi is administered by subcutaneous injection.
The injection should be administered in the thigh or abdomen. Patients should not inject into areas where the skin is tender, bruised, erythematous, indurated, affected by psoriasis or damaged.
Patients may self-inject Skyrizi after training in subcutaneous injection technique. Patients should be instructed to read the 'Instructions for use' provided in the package leaflet before administration.
Administration of Skyrizi in the upper, outer arm may only be performed by a healthcare professional or caregiver.
600 mg: For intravenous infusion.
Skyrizi concentrate for solution for infusion is for intravenous use only. The 600 mg dose should be administered over at least one hour. For instructions on dilution of the medicinal product before administration, see Special precautions for disposal and other handling under Cautions for Usage.

In the event of overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted immediately.

Hypersensitivity to the active substance or to any of the excipients listed in Description.
Clinically important active infections (e.g. active tuberculosis, see Precautions).

Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Infections: Risankizumab may increase the risk of infection.
In patients with a chronic infection, a history of recurrent infection, or known risk factors for infection, risankizumab should be used with caution. Treatment with risankizumab should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.
Patients treated with risankizumab should be instructed to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops such an infection or is not responding to standard therapy for the infection, the patient should be closely monitored and risankizumab should not be administered until the infection resolves.
Tuberculosis: Prior to initiating treatment with risankizumab, patients should be evaluated for tuberculosis (TB) infection. Patients receiving risankizumab should be monitored for signs and symptoms of active TB. Anti-TB therapy should be considered prior to initiating risankizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed.
Immunisations: Prior to initiating therapy with risankizumab, completion of all appropriate immunisations should be considered according to current immunisation guidelines. If a patient has received live vaccination (viral or bacterial), it is recommended to wait at least 4 weeks prior to starting treatment with risankizumab. Patients treated with risankizumab should not receive live vaccines during treatment and for at least 21 weeks after treatment (see Pharmacology: Pharmacokinetics under Actions).
Hypersensitivity: Serious hypersensitivity reactions, including anaphylaxis, have been reported with use of risankizumab (see Adverse Reactions). If a serious hypersensitivity reaction occurs, administration of risankizumab should be discontinued immediately and appropriate therapy initiated.
Excipients with known effect: Polysorbate: Polysorbates may cause allergic reactions.
360 mg: This medicinal product contains 0.48 mg of polysorbate 20 in each 360 mg dose.
600 mg: This medicinal product contains 2 mg of polysorbate 20 in each 600 mg dose.
Sodium: This medicinal product contains less than 1 mmol sodium (23 mg) per pre-filled pen, cartridge or vial, that is to say, essentially 'sodium free'.
Effects on ability to drive and use machines: Risankizumab has no or negligible influence on the ability to drive and use machines.

Women of childbearing potential: Women of childbearing potential should use an effective method of contraception during treatment and for at least 21 weeks after treatment.
Pregnancy: There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of risankizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of risankizumab during pregnancy.
Breast-feeding: It is unknown whether risankizumab is excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, which decreases to low concentrations soon afterwards; consequently, a risk to the breast-fed infant cannot be excluded during this short period. A decision should be made whether to discontinue/abstain from risankizumab therapy, taking into account the benefit of breast-feeding to the child and the benefit of risankizumab therapy to the woman.
Fertility: The effect of risankizumab on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility.

Summary of the safety profile: The most frequently reported adverse reactions were upper respiratory infections (15.6% in Crohn's disease).
Tabulated list of adverse reactions: Adverse reactions for risankizumab from clinical studies (Table 10) 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); very rare (<1/10 000) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. (See Table 10.)

Click on icon to see table/diagram/image

Description of selected adverse reactions: 150 mg: 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 Precautions).
360 mg/600 mg: Psoriasis: Infections: Over the entire psoriasis programme including long-term exposure to risankizumab, the rate of infections was 75.5 events per 100 subject-years. 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 (see Precautions).
Crohn's disease: Overall, the safety profile observed in patients with Crohn's disease treated with risankizumab was consistent with the safety profile observed in patients across indications.
Infections: The rate of infections in the pooled data from the 12-week induction studies was 83.3 events per 100 subject-years in subjects treated with risankizumab 600 mg intravenously compared to 117.7 events per 100 subject-years in placebo. The rate of serious infections was 3.4 events per 100 subject-years in subjects treated with risankizumab 600 mg intravenously compared to 16.7 events per 100 subject-years in placebo (see Precautions).
The rate of infections in the 52-week maintenance study was 57.7 events per 100 subject-years in subjects treated with risankizumab 360 mg subcutaneously after risankizumab induction compared to 76.0 events per 100 subject-years in subjects who received placebo after risankizumab induction. The rate of serious infections was 6.0 events per 100 subject-years in subjects treated with risankizumab 360 mg subcutaneously after risankizumab induction compared to 5.0 events per 100 subject-years in subjects who received placebo after risankizumab induction (see Precautions).
Immunogenicity: For subjects with Crohn's disease treated with risankizumab at the recommended intravenous induction and subcutaneous maintenance doses for up to 64 weeks in CD clinical trials, treatment-emergent anti-drug antibodies and neutralizing antibodies were detected in 3.4% (2/58) and 0% (0/58) of evaluated subjects, respectively.
Antibodies to risankizumab including neutralizing antibodies were not associated with changes in clinical response or safety.
Psoriatic arthritis: 150 mg: 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. Healthcare professionals are asked to report any suspected adverse reactions according to the local requirements.

Risankizumab is not expected to undergo metabolism by hepatic enzymes or renal elimination. Interactions between risankizumab and inhibitors, inducers, or substrates of medicinal product metabolising enzymes are not expected, and no dose adjustment is needed (see Pharmacology: Pharmacokinetics under Actions).
Concomitant immunosuppressive therapy or phototherapy: The safety and efficacy of risankizumab in combination with immunosuppressants, including biologics or phototherapy, have not been evaluated.

Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except those mentioned in Special precautions for disposal and other handling as follows.
Special precautions for disposal and other handling: Each pre-filled pen/on-body injector with cartridge/vial is for single use only.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
150 mg/360 mg: Before injecting, the carton should be removed from the refrigerator and allow to reach room temperature out of direct sunlight for 30 to 90 minutes without removing the pre-filled pen from the carton or for 45 to 90 minutes without removing the cartridge from the carton.
The solution should be colourless to yellow and clear to slightly opalescent.
General special precautions: Prior to use, a visual inspection of each pre-filled pen/cartridge is recommended. For the pre-filled pen (150 mg), the solution may contain a few translucent to white product-related particles. For the solution for injection (360 mg), the solution is free from foreign particles and practically free from product-related particles. Skyrizi should not be used if the solution is cloudy or discoloured, or contains large particles. Do not shake the pre-filled pen/cartridge.
Comprehensive instructions for use are provided in the package leaflet.
600 mg: The solutions should be visually inspected for particulate matter or discoloration prior to administration. The solution should be colourless to slightly yellow and clear to slightly opalescent. The liquid may contain tiny white or clear particles. The medicinal product and its dilutions should not be used if the solution is discoloured or cloudy, or if foreign particulate matter is present.
Instructions for dilution: This medicinal product should be prepared by a healthcare professional using aseptic technique. It must be diluted before administration.
The solution for infusion is prepared by dilution of the concentrate into an intravenous infusion bag or glass bottle containing 5% dextrose in water (D5W) or sodium chloride 9 mg/mL (0.9%) solution for infusion to a final concentration of approximately 1.2 mg/mL to 6 mg/mL. Refer to the table as follows for dilution instructions based on patient's indication. (See Table 11.)

Click on icon to see table/diagram/image

Prior to the start of the intravenous infusion, the content of the intravenous infusion bag or glass bottle should be at room temperature.
Infuse the diluted solution over a period of at least one hour for the 600 mg dose.
The solution in the vial and the dilutions should not be shaken.

Shelf life: 600 mg: Diluted solution for intravenous infusion: Chemical and physical in-use stability has been demonstrated for 20 hours at 2°C to 8°C (protected from light) or up to 8 hours at room temperature (protected from sunlight). Storage time at room temperature begins once the diluted solution has been prepared. The infusion should be completed within 8 hours after dilution in the infusion bag. Exposure to indoor light is acceptable during room temperature storage and administration.
From a microbiological point of view, the prepared infusion should be used immediately. If not used immediately, in-use storage time and conditions prior to use are the responsibility of the user and should not be longer than 20 hours at 2°C to 8°C.
Do not freeze.
Special precautions for storage: Store in a refrigerator (2°C-8°C). Do not freeze.
Keep the pre-filled pen/cartridge/vial in the outer carton in order to protect from light.
The pre-filled pen/cartridge may be stored out of the refrigerator (up to a maximum of 25°C) for up to 24 hours in the original carton.

Instructions for use: Important information to know before you inject Skyrizi: You should receive training on how to inject Skyrizi before giving an injection. Talk to your doctor, pharmacist or nurse if you need help.
Mark the dates on your calendar so you know when to inject Skyrizi.
Keep Skyrizi in the original carton to protect the medicine from light until it is time to use it.
Do not inject if the liquid in the inspection window is cloudy or contains flakes or large particles. The liquid should look clear to yellow and may contain tiny white or clear particles.
Do not shake the pen, carton, cartridge or on-body injector.
150 mg: Take the carton out of the refrigerator and leave it at room temperature, out of direct sunlight, for 30 to 90 minutes before injecting.
Wait to remove the dark grey cap until just before the injection.
Return this medicine to the pharmacy: if the expiry date (EXP) has passed; if the liquid has ever been frozen (even if thawed); if the pen has been dropped or damaged; if the carton perforations are broken.
360 mg: The single use on-body injector is designed for use with Skyrizi cartridge only.
Take the carton out of the refrigerator and leave it at room temperature, out of direct sunlight, for at least 45 up to 90 minutes before injecting.
Do not let the on-body injector get wet with water or any other liquids.
Do not touch the start button until you place the on-body injector loaded with the cartridge onto your skin and are ready to inject: You can only press the start button one time.
Physical activity should be limited during the injection process. Moderate physical activities can be done, such as walking, reaching and bending.
Do not delay in injecting the medicine after loading the cleaned cartridge into the on-body injector. Waiting will dry out the medicine and the on-body injector will not work afterwards.
Do not re-use the cartridge or the on-body injector.
Return this medicine to the pharmacy: if the expiry date (EXP) has passed; if the liquid has ever been frozen (even if thawed); if the cartridge or on-body injector has been dropped or damaged; if the carton perforations are broken; if the white paper tray cover is broken or missing.
Follow the steps as follows each time you use Skyrizi: 150 mg: STEP 1: Take the carton out of the refrigerator and leave it at room temperature, out of direct sunlight, for 30 to 90 minutes before injecting. Do not remove the pen from the carton while allowing Skyrizi to reach room temperature. Do not warm Skyrizi in any other way. For example, do not warm it in a microwave or in hot water. Do not use the pen if liquid has been frozen, even if it has been thawed.
STEP 2: Place the following items on a clean, flat surface: 1pre-filled pen; 1 alcohol pad (not included in the carton); 1 cotton ball or gauze pad (not included in the carton); special disposal container (not included in the carton).
Wash and dry your hands.
STEP 3: Choose from these 3 areas to inject: front of left thigh; front of right thigh; your belly (abdomen) at least 5 cm from your belly button (navel).
Before the injection, wipe where you will inject in a circular motion with an alcohol pad. Do not touch or blow on the injection site after it is cleaned. Allow the skin to dry before injecting. Do not inject through clothes. Do not inject into skin that is sore, bruised, red, hard, scarred, or has stretch marks. Do not inject into areas affected by psoriasis.
STEP 4: Hold the pen with the dark grey cap pointing up. Pull the dark grey cap straight off. Throw the dark grey cap away.
Check the liquid through the inspection window. It is normal to see bubbles in the liquid. The liquid should look clear to yellow and may contain tiny white or clear particles. Do not use if the liquid is cloudy or contains flakes or large particles.
STEP 5: Hold the pen with your fingers on the grey hand grips.
Turn the pen so that the white needle sleeve points toward the injection site and you can see the green activator button.
Gently squeeze the skin at your injection site to make a raised area and hold it firmly.
Place the white needle sleeve straight (90° angle) against the raised injection site.
STEP 6: Hold the pen so that you can see the green activator button and inspection window.
Push and keep pressing the pen down against the raised injection site. The pen will activate only if the white needle sleeve is pressed down against the injection site before pressing the green activator button.
Press the green activator button and hold the pen for 15 seconds. A loud "click" means the start of the injection.
STEP 7: Keep pressing the pen down against the injection site.
The injection is complete when: the pen has made a second "click" or; the yellow indicator has filled the inspection window.
This takes up to 15 seconds.
STEP 8: When the injection is complete, slowly pull the pen out from the skin.
The white needle sleeve will cover the needle tip and make another "click".
After completing the injection, place a cotton ball or gauze pad on the skin at the injection site. Do not rub the injection site. Slight bleeding at the injection site is normal.
STEP 9: Throw away the used pen in a special disposal container straight after use. Do not throw away the used pen in the household waste. Your doctor, pharmacist or nurse will tell you how to return the full special disposal container.
360 mg: STEP 1: Get ready. Take the carton out of the refrigerator and leave it at room temperature, out of direct sunlight, for at least 45 up to 90 minutes before injecting. Check expiry date (EXP) on the carton. Do not use Skyrizi if the expiry date (EXP) has passed. Do not remove the cartridge or on-body injector from the carton while allowing Skyrizi to reach room temperature. Do not warm Skyrizi in any other way. For example, do not warm it in a microwave or in hot water.
Gather all supplies and wash your hands. Place the following items on a clean, flat surface: plastic tray containing 1 on-body injector and 1 cartridge; 2 alcohol pads (not included in the carton); 1 cotton ball or gauze pad (not included in the carton); special disposal container (not included in the carton).
Wash and dry your hands.
Remove the white paper tray seal. Locate the black arrow. Peel away the white paper tray seal from the plastic tray.
Lift the plastic cover. Locate the rounded opening on the top cover. Insert your index finger in the opening and place your thumb on the opposite side. Lift the cover to remove and set it aside.
Inspect the on-body injector. Check that the on-body injector is intact and not damaged. The grey door should be slightly open. If the grey door does not open, press in firmly on the grey door ridges (left side of door) and swing open the door. Do not close the grey door before the cartridge is loaded. Do not use on-body injector if you drop it, discover missing pieces, or if it's damaged. Do not touch the grey start button until it is time to inject. It can be pressed one time only. Do not touch the needle cover area or needle.
If the grey start button is pressed before placing it on your body, the on-body injector can no longer be used. If this happens, speak to your doctor, pharmacist or nurse.
STEP 2: Set up on-body injector. Fully open the grey door. Avoid touching the needle cover area on the back of the on-body injector. The needle is behind the needle cover. Swing the grey door all the way to the right to open it. If the grey door does not open, press in firmly on the grey door ridges (left side of door) and swing open the door. Do not close the grey door before the cartridge is loaded.
Put the on-body injector aside.
Inspect the cartridge. Carefully remove the cartridge from the plastic tray. Do not twist or remove cartridge top.
Check the cartridge. The liquid should look clear to yellow and may contain tiny white or clear particles. It is normal to see one or more bubbles. Do not use if the liquid is cloudy, discoloured, or contains flakes or large particles. The cartridge parts and the clear plastic are not cracked or broken. Do not use if the liquid has been frozen (even if thawed). Do not use the cartridge if you drop it, discover missing pieces, or it is damaged.
Clean the smaller bottom tip of the cartridge. Locate the smaller bottom tip of the cartridge. Clean smaller bottom tip of the cartridge with an alcohol pad. Make sure to use the alcohol pad to clean the centre of the smaller bottom tip of the cartridge. Do not touch the smaller bottom tip of the cartridge after cleaning.
Load the cleaned cartridge into the on-body injector. Do not twist or remove the cartridge top. Insert the smaller bottom tip of the cartridge into the on-body injector first.
Firmly push down on the cartridge top until you hear a "click". After loading the cartridge, you may see a few drops of medicine on the back of the on-body injector. This is normal.
Make sure to proceed to the next step without delay. Waiting will dry out the medicine.
Close the grey door. Swing the grey door to the left, then squeeze firmly and listen for the grey door to "snap" shut. The grey door should stay locked after loading the cartridge. Do not close the grey door if the cartridge is not fully inserted or is missing. Proceed without delay to the next step.
STEP 3: Prepare to inject. Choose and clean your injection site. Choose from these 3 areas to inject: front of left thigh; front of right thigh; your belly (abdomen) at least 5 cm from your belly button (navel).
Do not inject into areas of the skin that naturally fold or bulge because the on-body injector could fall off during wear.
Before the injection, wipe where you will inject in a circular motion with an alcohol pad. Do not touch or blow on the injection site after it is cleaned. Allow the skin to dry before placing the on-body injector on the skin. Do not inject through clothes. Do not inject into skin that is sore, bruised, red, hard, scarred, or has stretch marks, moles or excessive hair. You can trim the excessive hair from the injection site.
Peel both tabs to expose skin adhesive. Turn the on-body injector over to find both green pull tabs. Avoid touching the needle cover (needle inside).
Peel away the large section using the green pull tab to expose the skin adhesive.
Peel away the small section using the green pull tab to expose the skin adhesive. This will remove the clear plastic strip, activating the on-body injector.
Check the status light when the on-body injector beeps. The status light will flash blue when the on-body injector is activated. If the status light does not flash blue, speak to your doctor, pharmacist or nurse. Do not press the grey start button yet. Do not touch the needle cover or the needle. Do not pull the adhesive material off on-body injector or allow the sticky side to fold and stick to itself.
The Skyrizi on-body injector must be placed on the skin and injection must be started within 30 minutes after removing the green pull tabs or it will not work. Make sure to proceed to next step without delay.
If the status light flashes red, the on-body injector is not working properly. Do not continue to use it. Speak to your doctor, pharmacist or nurse for assistance. If the on-body injector is attached to your body, carefully remove it from your skin.
Prepare the on-body injector for placement. For the belly (abdomen), move and hold the skin to create a firm, flat surface for injection at least 5 cm from your belly button (navel). Make sure to sit up straight to avoid skin folds and bulges. You do not need to pull the skin flat for the front of left thigh or right thigh.
Make sure to place the on-body injector so that you can see the blue status light.
Place the on-body injector on your skin. When the blue light flashes, the on-body injector is ready. Place the on-body injector onto the cleaned skin with the status light visible. Do not place the on-body injector on clothes. Only place on bare skin. Run your finger around the adhesive material to secure it. Do not move or adjust the on-body injector after it has been placed on your skin.
Proceed without delay to the next step.
STEP 4: Inject Skyrizi. Start injection. Firmly press and release the grey start button. You will hear a "click" and may feel a needle pinch. Check the status light when the on-body injector beeps. After starting the injection, the status light will continuously flash green. After starting the injection, you will hear pumping sounds as the on-body injector delivers the medicine.
Do not continue to use the on-body injector if status light flashes red. Carefully remove from skin if the status light flashes red. If this happens, speak to your doctor, pharmacist or nurse.
Wait for the injection to finish. It may take up to 5 minutes to complete the full dose of medicine. The on-body injector will automatically stop when the injection is finished. During the injection, the status light will continue to flash green. During the injection, you will hear pumping sounds as the on-body injector continues delivering the medicine.
During the injection, moderate physical activities can be done, such as walking, reaching and bending.
Do not continue to use the on-body injector if the status light flashes red. Carefully remove it from the skin if the status light flashes red. If this happens, speak to your doctor, pharmacist or nurse.
Injection is complete when: The on-body injector stops on its own. You hear a beep and the status light changes to solid green. If the status light has changed to solid green, this means that the injection is complete.
Remove the on-body injector. Do not put your fingers on the back side of the on-body injector when removing it from your skin. When the injection is done, grab the corner of the adhesive to carefully peel the on-body injector from the skin. Avoid touching the needle cover or needle on the back of the on-body injector. After removing the on-body injector, you will hear several beeps and the status light will turn off. The needle cover will cover the needle when the on-body injector is removed from the skin. It is normal to see a few small drops of liquid on your skin after removing the on-body injector. Press a cotton ball or gauze pad over the injection site on your skin and hold for 10 seconds. Do not rub the injection site. Slight bleeding at the injection site is normal.
Proceed to the next step.
STEP 5: Finish. Check the on-body injector. Inspect the medicine window and status light.
Check to see that the white plunger fills the entire medicine window and the solid green light turns off, letting you know that all the medicine has been injected. If the white plunger does not fill the window, speak to your doctor, pharmacist or nurse.
Disposal: Throw away the used on-body injector in a special disposal container straight after use. The on-body injector contains batteries, electronics, and a needle. Leave the cartridge in the on-body injector. Do not throw away the used on-body injector in the household waste. Your doctor, pharmacist or nurse will tell you how to return the full special disposal container. There may be local guidelines for disposal.

Immunosuppressants / Psoriasis, Seborrhea & Ichthyosis Preparations

L04AC18 - risankizumab ; Belongs to the class of interleukin inhibitors. Used as immunosuppressants.

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