Irish reimbursement granted for RINVOQ® (upadacitinib)

Irish reimbursement granted for RINVOQ® (upadacitinib), an oral JAK inhibitor approved for the treatment of both adults and adolescents ≥12 years* with moderate to severe Atopic Dermatitis1

  • Irish health authorities approve reimbursement for upadacitinib. It is for use in moderate to severe atopic dermatitis patients, for both adults and adolescents ≥12 years*
  • Upadacitinib received EU approval in August 2021 following a submission supported by data from one of the largest registrational Phase 3 programs in atopic dermatitis evaluating upadacitinib as monotherapy or with topical corticosteroids1

AbbVie has announced the availability in Ireland of upadacitinib, an oral, selective and reversible Janus Kinase (JAK) inhibitor. It is for the treatment of moderate to severe atopic dermatitis in adults and adolescents 12 years and older who are candidates for systemic therapy.1 This is now available to prescribe via the HSE-Medicines Management Programme under a HSE-Managed Access Protocol­­­­­­.**13

On August 24 last, the European Commission (EC) approved a recommended dose of upadacitinib for atopic dermatitis in adults. This is of 15 mg or 30 mg once daily based on individual patient presentation. 15 mg once daily for adolescents (12-17 years of age) and adults 65 years and older.1 Upadacitinib can be used with or without topical corticosteroids (TCS).1

The EC approval was supported by data from one of the largest registrational Phase 3 programs in atopic dermatitis with more than 2,500 adults and adolescents with moderate to severe disease.1 These studies evaluated the efficacy and safety of upadacitinib monotherapy (Measure Up 1 [MU1] and Measure Up 2 [MU2]) and with topical corticosteroids (AD Up [AU]) compared to placebo.1 In all three studies, the co-primary endpoints were at least a 75 percent improvement in the Eczema Area and Severity Index (EASI 75). It validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0/1 (clear or almost clear) at week 16.1

Professor of Dermatology, Trinity College Dublin, Ireland spoke about it

Alan Irvine was a upadacitinib clinical study investigator. He welcomed the availability of a new treatment option for Irish patients with atopic dermatitis.

He stated: “Eczema is a chronic relapsing inflammatory skin disease. It is characterised by intense itch, dry skin and typically distributed skin lesions. The burden experienced by patients as well as their care-givers is significant, with chronic itch and sleep disturbance. It therefore negatively affects the overall quality of life.

“Clinicians need more tools to help them treat and manage this complex disease. It is very welcome to now have an additional treatment option in upadacitinib available for moderate to severe atopic dermatitis patients in Ireland. The degree and early onset of skin clearance in addition to itch relief in the upadacitinib Phase 3 clinical studies are very encouraging.

AbbVie’s Irish General Manager spoke about it.

Andres Rodrigo said: “I very much welcome the HSE’s timely approval of upadacitinib for patients with atopic dermatitis, which is a highly debilitating condition with limited therapeutic options currently.  Ireland will be among the first European countries to provide access to upadacitinib for atopic dermatitis. It was approved by the EMA in August 2021.

“It will provide significant improvement to patient’s quality of life, impacting positively on both their physical and psychological well-being.1 Our company’s Irish employees support the manufacture of upadacitinib for global supply. It is very encouraging that locally made innovation is being made available to Irish citizens.”

* The recommended dose of upadicitinib is 15mg once daily for adolescents weighing at least 30kg.  The safety and efficacy of RINVOQ in children with atopic dermatitis below the age of 12 years have not been established. No data are available. No clinical exposure data are available in adolescents <40kg. The posology in adolescent patients 30kg to <40kg was determined using population pharmacokinetic modelling and simulation.1

**Reimbursement of RINVOQ on the High-Tech Arrangement under a managed access protocol is confined to the treatment of moderate-to-severe refractory AD in adults and
adolescents 12 years and older for whom immunosuppressant treatment has failed or is not tolerated or is contraindicated. The prescribing of RINVOQ under the High-Tech
Arrangement is confined to consultant dermatologists who have agreed to the terms of the HSE-Managed Access Protocol and have been approved by the HSE-Medicines
Management Programme.13

About upadacitinib

Discovered and developed by AbbVie scientists, upadacitinib is a selective and reversible JAK inhibitor. It is being studied in several immune-mediated inflammatory diseases.1,212

In human cellular assays, upadacitinib preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2.1 Upadacitinib 15mg and 30mg is approved by the U.S. Food and Drug Administration (FDA) for the treatment of moderate to severe atopic dermatitis in adults and children 12 years of age and older.

Upadacitinib 15mg is also approved by the U.S. Food and Drug Administration (FDA) for adults with moderately to severely active rheumatoid arthritis. Also by the European Commission for adults with moderate to severe active rheumatoid arthritis, adults with active psoriatic arthritis (PsA) and adults with active ankylosing spondylitis (AS).

Phase 3 trials of upadacitinib in rheumatoid arthritis, atopic dermatitis, psoriatic arthritis, axial spondyloarthritis, Crohn’s disease, ulcerative colitis, giant cell arteritis in addition to Takayasu arteritis are ongoing.312

Important EU Indications and Safety Information about upadacitinib1

Rheumatoid arthritis:

Upadacitinib is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). Upadacitinib may be used as monotherapy or in combination with methotrexate.

Psoriatic arthritis:

Upadacitinib is indicated for the treatment of active psoriatic arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more DMARDs. Upadacitinib may be used as monotherapy or in combination with methotrexate.

Ankylosing spondylitis:

Upadacitinib is indicated for the treatment of active ankylosing spondylitis in adult patients who have responded inadequately to conventional therapy.

Atopic dermatitis:

Upadacitinib is indicated for the treatment of moderate to severe atopic dermatitis in adults and adolescents 12 years and older who are candidates for systemic therapy.

Contraindications1

Upadacitinib is contraindicated in patients hypersensitive to the active substance or to any of the excipients, in patients with active tuberculosis (TB) or active serious infections, in patients with severe hepatic impairment, and during pregnancy.

Special warnings and precautions for use1
Immunosuppressive medicinal products:

Use in combination with other potent immunosuppressants is not recommended.

Serious infections:

Serious and sometimes fatal infections have been reported in patients receiving upadacitinib. The most frequent serious infections reported included pneumonia as well as cellulitis. Cases of bacterial meningitis have been reported. Among opportunistic infections, TB, multidermatomal herpes zoster, oral/esophageal candidiasis, and cryptococcosis have been reported with upadacitinib. As there is a higher incidence of infections in patients ≥65 years of age, caution should be used when treating this population.

Viral reactivation:

Viral reactivation, including cases of herpes zoster, was reported in clinical studies. Therefore, the risk of herpes zoster appears to be higher in Japanese patients treated with upadacitinib.

Vaccinations:

The use of live, attenuated vaccines during or immediately prior to therapy is not recommended. Therefore, it is recommended that patients be brought up to date with all immunizations. This is including prophylactic zoster vaccinations, prior to initiating upadacitinib, in agreement with current immunization guidelines.

Malignancy:

The risk of malignancies, including lymphoma is increased in patients with rheumatoid arthritis (RA). Malignancies, including nonmelanoma skin cancer (NMSC), have been reported in patients treated with upadacitinib. Consider the risks and benefits of upadacitinib treatment prior to initiating therapy in patients with a known malignancy other than a successfully treated NMSC or when considering continuing upadacitinib therapy in patients who develop a malignancy.

Hematological abnormalities:

Treatment should not be initiated, or should be temporarily interrupted, in patients with hematological abnormalities observed during routine patient management.

Cardiovascular risk:

RA patients have an increased risk for cardiovascular disorders. Patients treated with upadacitinib should have risk factors (e.g., hypertension, hyperlipidemia) managed as part of usual standard of care.

Lipids:

Upadacitinib treatment was associated with dose-dependent increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, as well as high-density lipoprotein cholesterol.

Hepatic transaminase elevations:

Treatment with upadacitinib was associated with an increased incidence of liver enzyme elevation compared to placebo

Venous thromboembolisms:

Events of deep vein thrombosis (DVT) in addition to pulmonary embolism (PE) have been reported in patients receiving JAK inhibitors, including upadacitinib. Therefore, upadacitinib should be used with caution in patients at high risk for DVT/PE.

Adverse reactions1

The most commonly reported adverse reactions in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis clinical trials (≥2% of patients in at least one of the indications) with upadacitinib 15 mg were upper respiratory tract infections, blood creatine phosphokinase (CPK) increased, alanine transaminase increased, bronchitis, nausea, cough, aspartate transaminase increased, and hypercholesterolemia.

Overall, the most commonly reported adverse reactions in atopic dermatitis trials (≥2% of patients) with upadacitinib 15 mg or 30 mg were:

  • Upper respiratory tract infection
  • Acne
  • Herpes simplex
  • Headache
  • CPK increased
  • Cough
  • Folliculitis
  • Abdominal pain
  • Nausea
  • Neutropenia
  • Pyrexia
  • Influenza.
Ankylosing spondylitis:

Overall, the safety profile observed in patients with active ankylosing spondylitis treated with upadacitinib 15 mg was consistent with the safety profile observed in patients with RA.

Psoriatic arthritis:

Overall, the safety profile observed in patients with active psoriatic arthritis treated with upadacitinib 15 mg was consistent with the safety profile observed in patients with RA. A higher incidence of acne and bronchitis was observed in patients treated with upadacitinib 15 mg (1.3% and 3.9%, respectively). This is compared to placebo (0.3% and 2.7%, respectively). A higher rate of serious infections (2.6 events per 100 patient-years and 1.3 events per 100 patient-years, respectively) and hepatic transaminase elevations (ALT elevations Grade 3 and higher rates 1.4% and 0.4%, respectively) was observed in patients treated with upadacitinib in combination with MTX therapy compared to patients treated with monotherapy. There was a higher rate of serious infections in patients ≥65 years of age, although data are limited.

Atopic dermatitis:

Dose-dependent changes in ALT increased and/or AST increased (≥ 3 x ULN), lipid parameters, CPK values (> 5 x ULN), and neutropenia (ANC < 1 x 102 cells/L) associated with upadacitinib treatment were similar to what was observed in the rheumatologic disease clinical studies. Based on limited data in atopic dermatitis patients aged 65 years and older, there was a higher rate of overall adverse reactions with the upadacitinib 30 mg dose compared to the 15 mg dose. The safety profile for upadacitinib 15 mg in adolescents was similar to that in adults. The safety and efficacy of the 30 mg dose in adolescents are still being investigated.

This is not a complete summary of all safety information.

Therefore, please see the upadacitinib full SmPC for complete prescribing information at www.medicines.ie

Read our Latest News

Leave a Reply

Your email address will not be published. Required fields are marked *

Please Confirm

This website is only for the eyes of medical professionals. Are you a medical professional?