- Approval Id
- 2710dbdabdc313e1
- Drug Approval Emc Name
- Skyrizi 150 mg solution for injection in pre-filled pen
- Drug Name
- Skyrizi 150 mg solution for injection in pre-filled pen
- Company Address
- AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, SL6 4UB, UK
- Company Website
- //www.abbvie.co.uk
- Company Telephone
- +44 (0)1628 561 090
- Company Medical Info Direct Line
- +44 (0)1628 561 092
- Company Medical Info Email
- ukmedinfo@abbvie.com
- Atc Code
- L04AC18
- Legal Category
- Prescription only medicine
- Authorisation Holder
- AbbVie Ltd
Maidenhead
SL6 4UB
UK
- Authorisation Number
- PLGB 41042/0045
- Authorisation Date
- 01 March 2024
- Instruction Authorisation Holder
- AbbVie Ltd
Maidenhead
SL6 4UB
UK
- Instruction Authorisation Number
- PLGB 41042/0045
- Instruction Authorisation Date
- 01 March 2024
- Instruction Composition
- Each pre-filled pen contains 150 mg risankizumab in 1 mL solution.
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.
- Instruction Dosage Form
- Solution for injection (injection)
The solution is colourless to slightly yellow and clear to slightly opalescent.
- Instruction Clinical Particulars
- 4.1 Therapeutic indications
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).4.2 Posology and method of administration
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
The recommended dose is 150 mg administered as a subcutaneous injection at week 0, week 4, and every 12 weeks thereafter (either as two 75 mg pre-filled syringe injections or one 150 mg pre-filled pen or pre-filled syringe injection).
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.
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 section 5.2).
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 section 5.2).
\*Paediatric population\*
The safety and efficacy of risankizumab in children and adolescents aged 5 to less than 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.
\*Overweight patients\*
No dose adjustment is required (see section 5.2).
Method of administration
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, or affected by psoriasis.
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.4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Clinically important active infections (e.g. active tuberculosis, see section 4.4).4.4 Special warnings and precautions for use
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 section 5.2).
Hypersensitivity
Serious hypersensitivity reactions, including anaphylaxis, have been reported with use of risankizumab (see section 4.8). If a serious hypersensitivity reaction occurs, administration of risankizumab should be discontinued immediately and appropriate therapy initiated.
Excipients with known effect
This medicinal product contains less than 1 mmol sodium (23 mg) per 150 mg dose, that is to say, essentially 'sodium free'.4.5 Interaction with other medicinal products and other forms of interaction
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 section 5.2).
Concomitant immunosuppressive therapy or phototherapy
The safety and efficacy of risankizumab in combination with immunosuppressants, including biologics or phototherapy, have not been evaluated.4.6 Fertility, pregnancy and lactation
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.4.7 Effects on ability to drive and use machines
Risankizumab has no or negligible influence on the ability to drive and use machines.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) 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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
\*\*Table 1: List of adverse reactions\*\*
| | | |
| --- | --- | --- |
| \*\*System Organ Class\*\* | \*\*Frequency\*\* | \*\*Adverse reactions\*\* |
| Infections and infestations | Very common | Upper respiratory infectionsa |
| Common | Tinea infectionsb |
| Uncommon | Folliculitis |
| Nervous system disorders | Common | Headachec |
| Skin and subcutaneous tissue disorders | Common | Pruritus Rash Eczema |
| Uncommon | Urticaria |
| General disorders and administration site conditions | Common | Fatigued Injection site reactionse |
| Immune system disorders | Rare | Anaphylactic reactions |
| 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).
\*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 subjects exposed to long term treatment of risankizumab in the extension study, the immunogenicity profile observed up to 204 weeks of treatment was consistent compared to the first 52 weeks of treatment.
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.
\*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.
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 via the Yellow Card Scheme:
Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store4.9 Overdose
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.
- Instruction Pharmacology
- 5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC18
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.
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. Patients who completed these studies and other Phase 2/3 studies had the opportunity to enrol in an open-label extension study, LIMMITLESS.
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 2 and Figure 1.
\*\*Table 2: Efficacy and quality of life results in adults with plaque psoriasis in ULTIMMA-1 and ULTIMMA-2\*\*
| | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | \*\*ULTIMMA-1\*\* | | | \*\*ULTIMMA-2\*\* | | |
| \*\*Risankizumab\*\* \*\*(N=304)\*\* \*\*n (%)\*\* | \*\*Ustekinumab\*\* \*\*(N=100)\*\* \*\*n (%)\*\* | \*\*Placebo\*\* \*\*(N=102)\*\* \*\*n (%)\*\* | \*\*Risankizumab\*\* \*\*(N=294)\*\* \*\*n (%)\*\* | \*\*Ustekinumab\*\* \*\*(N=99)\*\* \*\*n (%)\*\* | \*\*Placebo\*\* \*\*(N=98)\*\* \*\*n (%)\*\* |
| \*\*sPGA of clear or almost clear (0 or 1)\*\* | | | | | | |
| \*\*Week 16a\*\* | 267 (87.8) | 63 (63.0) | 8 (7.8) | 246 (83.7) | 61 (61.6) | 5 (5.1) |
| \*\*Week 52\*\* | 262 (86.2) | 54 (54.0) | -- | 245 (83.3) | 54 (54.5) | -- |
| \*\*sPGA of clear (0)\*\* | | | | | | |
| \*\*Week 16\*\* | 112 (36.8) | 14 (14.0) | 2 (2.0) | 150 (51.0) | 25 (25.3) | 3 (3.1) |
| \*\*Week 52\*\* | 175 (57.6) | 21 (21.0) | -- | 175 (59.5) | 30 (30.3) | -- |
| \*\*PASI 75\*\* | | | | | | |
| \*\*Week 12\*\* | 264 (86.8) | 70 (70.0) | 10 (9.8) | 261 (88.8) | 69 (69.7) | 8 (8.2) |
| \*\*Week 52\*\* | 279 (91.8) | 70 (70.0) | -- | 269 (91.5) | 76 (76.8) | -- |
| \*\*PASI 90\*\* | | | | | | |
| \*\*Week 16a\*\* | 229 (75.3) | 42 (42.0) | 5 (4.9) | 220 (74.8) | 47 (47.5) | 2 (2.0) |
| \*\*Week 52\*\* | 249 (81.9) | 44 (44.0) | -- | 237 (80.6) | 50 (50.5) | -- |
| \*\*PASI 100\*\* | | | | | | |
| \*\*Week 16\*\* | 109 (35.9) | 12 (12.0) | 0 (0.0) | 149 (50.7) | 24 (24.2) | 2 (2.0) |
| \*\*Week 52\*\* | 171 (56.3) | 21 (21.0) | -- | 175 (59.5) | 30 (30.3) | -- |
| \*\*DLQI 0 or 1b\*\* | | | | | | |
| \*\*Week 16\*\* | 200 (65.8) | 43 (43.0) | 8 (7.8) | 196 (66.7) | 46 (46.5) | 4 (4.1) |
| \*\*Week 52\*\* | 229 (75.3) | 47 (47.0) | -- | 208 (70.7) | 44 (44.4) | -- |
| \*\*PSS 0 (symptom-free)c\*\* | | | | | | |
| \*\*Week 16\*\* | 89 (29.3) | 15 (15.0) | 2 (2.0) | 92 (31.3) | 15 (15.2) | 0 (0.0) |
| \*\*Week 52\*\* | 173 (56.9) | 30 (30.0) | -- | 160 (54.4) | 30 (30.3) | -- |
| All comparisons of risankizumab versus ustekinumab and placebo achieved p<0.001 except for PASI 75 at week 52 in ULTIMMA-2 where p=0.001 a Co-primary endpoints versus placebo b No impact on health-related quality of life c Psoriasis Symptom Scale (PSS) of 0 means no symptoms of pain, itching, redness, and burning during the last 24 hours | | | | | | |
\*\*Figure 1: Time course of mean percent change from baseline of PASI in ULTIMMA-1 and ULTIMMA-2\*\*
RZB = risankizumab
UST = ustekinumab
PBO = placebo
p<0.001 at each time point
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.
\*\*Table 3: Mean changes from baseline in NAPSI, PPASI, and PSSI\*\*
| | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | \*\*ULTIMMA-1\*\* | | \*\*ULTIMMA-2\*\* | | \*\*IMMHANCE\*\* | |
| \*\*Risankizumab\*\* | \*\*Placebo\*\* | \*\*Risankizumab\*\* | \*\*Placebo\*\* | \*\*Risankizumab\*\* | \*\*Placebo\*\* |
| \*\*NAPSI:\*\* \*\*Change at Week 16 (SE)\*\* | N=178; -9.0 (1.17) | N=56; 2.1 (1.86)\\*\\*\\* | N=177; -7.5 (1.03) | N=49; 3.0 (1.76)\\*\\*\\* | N=235; -7.5 (0.89) | N=58; 2.5 (1.70)\\*\\*\\* |
| \*\*PPASI:\*\* \*\*Change at Week 16 (SE)\*\* | N=95; -5.93 (0.324) | N=34; -3.17 (0.445)\\*\\*\\* | N=86; -7.24 (0.558) | N=23; -3.74 (1.025)\\*\\* | N=113; -7.39 (0.654) | N=26; -0.27 (1.339)\\*\\*\\* |
| \*\*PSSI:\*\* \*\*Change at Week 16 (SE)\*\* | N=267; -17.6 (0.47) | N=92; -2.9 (0.69)\\*\\*\\* | N=252; -18.4 (0.52) | N=83; -4.6 (0.82)\\*\\*\\* | N=357; -20.1 (0.40) | N=88; -5.5 (0.77)\\*\\*\\* |
| \*\*NAPSI:\*\* \*\*Change at Week 52 (SE)\*\* | N=178; -15.7 (0.94) | - | N=183; -16.7 (0.85) | - | - | - |
| \*\*PPASI:\*\* \*\*Change at Week 52 (SE)\*\* | N=95; -6.16 (0.296) | - | N=89; -8.35 (0.274) | - | - | - |
| \*\*PSSI:\*\* \*\*Change at Week 52 (SE)\*\* | N=269; -17.9 (0.34) | - | N=259; -18.8 (0.24) | - | - | - |
| Nail Psoriasis Severity Index (NAPSI), Palmoplantar Psoriasis Severity Index (PPASI), Psoriasis Scalp Severity Index (PSSI), and Standard Error (SE) \\*\\* P < 0.01 comparing to risankizumab \\*\\*\\* P < 0.001 comparing to risankizumab | | | | | | |
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.
Of the patients who received risankizumab in ULTIMMA-1 and ULTIMMA-2, 525 continued to receive risankizumab every 12 weeks in LIMMITLESS. Of these, 376 (71.6%) completed an additional 252 weeks of open-label treatment. Among subjects remaining in the study, improvements achieved with risankizumab in rates of PASI 90 and sPGA of clear or almost clear at week 52 were maintained through week 304.
Of the patients who received ustekinumab in ULTIMMA-1 and ULTIMMA-2, 172 received risankizumab every 12 weeks in LIMMITLESS. Of these, 116 (67.4%) completed the study, including 252 weeks of open-label risankizumab treatment and end of study follow-up. Among subjects remaining in the study, rates of PASI 90 and sPGA response of clear or almost clear increased from week 52 through week 76 and were then maintained through week 304.
Figures 2 and 3 show the response rates for PASI 90 and sPGA of clear or almost clear, respectively, in subjects who completed 252 weeks of open-label treatment in LIMMITLESS.
\*\*Figure 2: Percent of subjects who achieved a PASI 90 response (OC) in LIMMITLESS\*\*
\*\*Figure 3: Percent of subjects who achieved an sPGA clear or almost clear response by visit (OC) in LIMMITLESS\*\*
Improvements in Dermatology Life Quality Index (DLQI 0 or 1) were maintained in patients receiving continuous risankizumab treatment through week 304 in the open label extension study LIMMITLESS.
The safety profile of risankizumab with more than 5 years 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 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:
• 130 kg). However, this observation is based on a limited number of subjects. 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 or psoriatic arthritis. No clinically meaningful differences in risankizumab exposure were observed in Chinese or Japanese subjects compared to Caucasian subjects in a clinical pharmacokinetic study in healthy volunteers.5.3 Preclinical safety data
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 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.
- Instruction Pharmaceutical Particulars
- 6.1 List of excipients
Sodium acetate trihydrate
Acetic acid
Trehalose dihydrate
Polysorbate 20
Water for injections6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.6.3 Shelf life
2 years6.4 Special precautions for storage
Store in a refrigerator (2ºC - 8ºC). Do not freeze.
Keep the pre-filled pen in the outer carton in order to protect from light.
Skyrizi 150 mg pre-filled pen may be stored out of the refrigerator (up to a maximum of 25ºC) for up to 24 hours in the original carton to protect from light.6.5 Nature and contents of container
Pre-filled glass syringe assembled in a pre-filled pen with an automatic needle sleeve.
Skyrizi 150 mg is available in packs containing 1 pre-filled pen.
Not all presentations may be marketed.6.6 Special precautions for disposal and other handling
Before injecting, patients should remove the carton from the refrigerator and allow to reach room temperature out of direct sunlight (30 to 90 minutes) without removing the pre-filled pen 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 the pre-filled pen is recommended. The solution may contain a few translucent to white 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.
Comprehensive instructions for use are provided in the package leaflet.
Each pre-filled pen is for single use only.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
- Instruction Content
- ## Composition
Each pre-filled pen contains 150 mg risankizumab in 1 mL solution.
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.
## Pharmaceutical Form
Solution for injection (injection)
The solution is colourless to slightly yellow and clear to slightly opalescent.
## Clinical Particulars
4.1 Therapeutic indications
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).4.2 Posology and method of administration
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
The recommended dose is 150 mg administered as a subcutaneous injection at week 0, week 4, and every 12 weeks thereafter (either as two 75 mg pre-filled syringe injections or one 150 mg pre-filled pen or pre-filled syringe injection).
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.
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 section 5.2).
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 section 5.2).
\*Paediatric population\*
The safety and efficacy of risankizumab in children and adolescents aged 5 to less than 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.
\*Overweight patients\*
No dose adjustment is required (see section 5.2).
Method of administration
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, or affected by psoriasis.
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.4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Clinically important active infections (e.g. active tuberculosis, see section 4.4).4.4 Special warnings and precautions for use
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 section 5.2).
Hypersensitivity
Serious hypersensitivity reactions, including anaphylaxis, have been reported with use of risankizumab (see section 4.8). If a serious hypersensitivity reaction occurs, administration of risankizumab should be discontinued immediately and appropriate therapy initiated.
Excipients with known effect
This medicinal product contains less than 1 mmol sodium (23 mg) per 150 mg dose, that is to say, essentially 'sodium free'.4.5 Interaction with other medicinal products and other forms of interaction
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 section 5.2).
Concomitant immunosuppressive therapy or phototherapy
The safety and efficacy of risankizumab in combination with immunosuppressants, including biologics or phototherapy, have not been evaluated.4.6 Fertility, pregnancy and lactation
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.4.7 Effects on ability to drive and use machines
Risankizumab has no or negligible influence on the ability to drive and use machines.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) 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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
\*\*Table 1: List of adverse reactions\*\*
| | | |
| --- | --- | --- |
| \*\*System Organ Class\*\* | \*\*Frequency\*\* | \*\*Adverse reactions\*\* |
| Infections and infestations | Very common | Upper respiratory infectionsa |
| Common | Tinea infectionsb |
| Uncommon | Folliculitis |
| Nervous system disorders | Common | Headachec |
| Skin and subcutaneous tissue disorders | Common | Pruritus Rash Eczema |
| Uncommon | Urticaria |
| General disorders and administration site conditions | Common | Fatigued Injection site reactionse |
| Immune system disorders | Rare | Anaphylactic reactions |
| 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).
\*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 subjects exposed to long term treatment of risankizumab in the extension study, the immunogenicity profile observed up to 204 weeks of treatment was consistent compared to the first 52 weeks of treatment.
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.
\*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.
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 via the Yellow Card Scheme:
Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store4.9 Overdose
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.
## Pharmacological Properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC18
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.
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. Patients who completed these studies and other Phase 2/3 studies had the opportunity to enrol in an open-label extension study, LIMMITLESS.
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 2 and Figure 1.
\*\*Table 2: Efficacy and quality of life results in adults with plaque psoriasis in ULTIMMA-1 and ULTIMMA-2\*\*
| | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | \*\*ULTIMMA-1\*\* | | | \*\*ULTIMMA-2\*\* | | |
| \*\*Risankizumab\*\* \*\*(N=304)\*\* \*\*n (%)\*\* | \*\*Ustekinumab\*\* \*\*(N=100)\*\* \*\*n (%)\*\* | \*\*Placebo\*\* \*\*(N=102)\*\* \*\*n (%)\*\* | \*\*Risankizumab\*\* \*\*(N=294)\*\* \*\*n (%)\*\* | \*\*Ustekinumab\*\* \*\*(N=99)\*\* \*\*n (%)\*\* | \*\*Placebo\*\* \*\*(N=98)\*\* \*\*n (%)\*\* |
| \*\*sPGA of clear or almost clear (0 or 1)\*\* | | | | | | |
| \*\*Week 16a\*\* | 267 (87.8) | 63 (63.0) | 8 (7.8) | 246 (83.7) | 61 (61.6) | 5 (5.1) |
| \*\*Week 52\*\* | 262 (86.2) | 54 (54.0) | -- | 245 (83.3) | 54 (54.5) | -- |
| \*\*sPGA of clear (0)\*\* | | | | | | |
| \*\*Week 16\*\* | 112 (36.8) | 14 (14.0) | 2 (2.0) | 150 (51.0) | 25 (25.3) | 3 (3.1) |
| \*\*Week 52\*\* | 175 (57.6) | 21 (21.0) | -- | 175 (59.5) | 30 (30.3) | -- |
| \*\*PASI 75\*\* | | | | | | |
| \*\*Week 12\*\* | 264 (86.8) | 70 (70.0) | 10 (9.8) | 261 (88.8) | 69 (69.7) | 8 (8.2) |
| \*\*Week 52\*\* | 279 (91.8) | 70 (70.0) | -- | 269 (91.5) | 76 (76.8) | -- |
| \*\*PASI 90\*\* | | | | | | |
| \*\*Week 16a\*\* | 229 (75.3) | 42 (42.0) | 5 (4.9) | 220 (74.8) | 47 (47.5) | 2 (2.0) |
| \*\*Week 52\*\* | 249 (81.9) | 44 (44.0) | -- | 237 (80.6) | 50 (50.5) | -- |
| \*\*PASI 100\*\* | | | | | | |
| \*\*Week 16\*\* | 109 (35.9) | 12 (12.0) | 0 (0.0) | 149 (50.7) | 24 (24.2) | 2 (2.0) |
| \*\*Week 52\*\* | 171 (56.3) | 21 (21.0) | -- | 175 (59.5) | 30 (30.3) | -- |
| \*\*DLQI 0 or 1b\*\* | | | | | | |
| \*\*Week 16\*\* | 200 (65.8) | 43 (43.0) | 8 (7.8) | 196 (66.7) | 46 (46.5) | 4 (4.1) |
| \*\*Week 52\*\* | 229 (75.3) | 47 (47.0) | -- | 208 (70.7) | 44 (44.4) | -- |
| \*\*PSS 0 (symptom-free)c\*\* | | | | | | |
| \*\*Week 16\*\* | 89 (29.3) | 15 (15.0) | 2 (2.0) | 92 (31.3) | 15 (15.2) | 0 (0.0) |
| \*\*Week 52\*\* | 173 (56.9) | 30 (30.0) | -- | 160 (54.4) | 30 (30.3) | -- |
| All comparisons of risankizumab versus ustekinumab and placebo achieved p<0.001 except for PASI 75 at week 52 in ULTIMMA-2 where p=0.001 a Co-primary endpoints versus placebo b No impact on health-related quality of life c Psoriasis Symptom Scale (PSS) of 0 means no symptoms of pain, itching, redness, and burning during the last 24 hours | | | | | | |
\*\*Figure 1: Time course of mean percent change from baseline of PASI in ULTIMMA-1 and ULTIMMA-2\*\*
RZB = risankizumab
UST = ustekinumab
PBO = placebo
p<0.001 at each time point
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.
\*\*Table 3: Mean changes from baseline in NAPSI, PPASI, and PSSI\*\*
| | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | \*\*ULTIMMA-1\*\* | | \*\*ULTIMMA-2\*\* | | \*\*IMMHANCE\*\* | |
| \*\*Risankizumab\*\* | \*\*Placebo\*\* | \*\*Risankizumab\*\* | \*\*Placebo\*\* | \*\*Risankizumab\*\* | \*\*Placebo\*\* |
| \*\*NAPSI:\*\* \*\*Change at Week 16 (SE)\*\* | N=178; -9.0 (1.17) | N=56; 2.1 (1.86)\\*\\*\\* | N=177; -7.5 (1.03) | N=49; 3.0 (1.76)\\*\\*\\* | N=235; -7.5 (0.89) | N=58; 2.5 (1.70)\\*\\*\\* |
| \*\*PPASI:\*\* \*\*Change at Week 16 (SE)\*\* | N=95; -5.93 (0.324) | N=34; -3.17 (0.445)\\*\\*\\* | N=86; -7.24 (0.558) | N=23; -3.74 (1.025)\\*\\* | N=113; -7.39 (0.654) | N=26; -0.27 (1.339)\\*\\*\\* |
| \*\*PSSI:\*\* \*\*Change at Week 16 (SE)\*\* | N=267; -17.6 (0.47) | N=92; -2.9 (0.69)\\*\\*\\* | N=252; -18.4 (0.52) | N=83; -4.6 (0.82)\\*\\*\\* | N=357; -20.1 (0.40) | N=88; -5.5 (0.77)\\*\\*\\* |
| \*\*NAPSI:\*\* \*\*Change at Week 52 (SE)\*\* | N=178; -15.7 (0.94) | - | N=183; -16.7 (0.85) | - | - | - |
| \*\*PPASI:\*\* \*\*Change at Week 52 (SE)\*\* | N=95; -6.16 (0.296) | - | N=89; -8.35 (0.274) | - | - | - |
| \*\*PSSI:\*\* \*\*Change at Week 52 (SE)\*\* | N=269; -17.9 (0.34) | - | N=259; -18.8 (0.24) | - | - | - |
| Nail Psoriasis Severity Index (NAPSI), Palmoplantar Psoriasis Severity Index (PPASI), Psoriasis Scalp Severity Index (PSSI), and Standard Error (SE) \\*\\* P < 0.01 comparing to risankizumab \\*\\*\\* P < 0.001 comparing to risankizumab | | | | | | |
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.
Of the patients who received risankizumab in ULTIMMA-1 and ULTIMMA-2, 525 continued to receive risankizumab every 12 weeks in LIMMITLESS. Of these, 376 (71.6%) completed an additional 252 weeks of open-label treatment. Among subjects remaining in the study, improvements achieved with risankizumab in rates of PASI 90 and sPGA of clear or almost clear at week 52 were maintained through week 304.
Of the patients who received ustekinumab in ULTIMMA-1 and ULTIMMA-2, 172 received risankizumab every 12 weeks in LIMMITLESS. Of these, 116 (67.4%) completed the study, including 252 weeks of open-label risankizumab treatment and end of study follow-up. Among subjects remaining in the study, rates of PASI 90 and sPGA response of clear or almost clear increased from week 52 through week 76 and were then maintained through week 304.
Figures 2 and 3 show the response rates for PASI 90 and sPGA of clear or almost clear, respectively, in subjects who completed 252 weeks of open-label treatment in LIMMITLESS.
\*\*Figure 2: Percent of subjects who achieved a PASI 90 response (OC) in LIMMITLESS\*\*
\*\*Figure 3: Percent of subjects who achieved an sPGA clear or almost clear response by visit (OC) in LIMMITLESS\*\*
Improvements in Dermatology Life Quality Index (DLQI 0 or 1) were maintained in patients receiving continuous risankizumab treatment through week 304 in the open label extension study LIMMITLESS.
The safety profile of risankizumab with more than 5 years 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 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:
• 130 kg). However, this observation is based on a limited number of subjects. 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 or psoriatic arthritis. No clinically meaningful differences in risankizumab exposure were observed in Chinese or Japanese subjects compared to Caucasian subjects in a clinical pharmacokinetic study in healthy volunteers.5.3 Preclinical safety data
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 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.
## Pharmaceutical Particulars
6.1 List of excipients
Sodium acetate trihydrate
Acetic acid
Trehalose dihydrate
Polysorbate 20
Water for injections6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.6.3 Shelf life
2 years6.4 Special precautions for storage
Store in a refrigerator (2ºC - 8ºC). Do not freeze.
Keep the pre-filled pen in the outer carton in order to protect from light.
Skyrizi 150 mg pre-filled pen may be stored out of the refrigerator (up to a maximum of 25ºC) for up to 24 hours in the original carton to protect from light.6.5 Nature and contents of container
Pre-filled glass syringe assembled in a pre-filled pen with an automatic needle sleeve.
Skyrizi 150 mg is available in packs containing 1 pre-filled pen.
Not all presentations may be marketed.6.6 Special precautions for disposal and other handling
Before injecting, patients should remove the carton from the refrigerator and allow to reach room temperature out of direct sunlight (30 to 90 minutes) without removing the pre-filled pen 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 the pre-filled pen is recommended. The solution may contain a few translucent to white 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.
Comprehensive instructions for use are provided in the package leaflet.
Each pre-filled pen is for single use only.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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