RINVOQ®, the 15mg once-daily oral selective & reversible JAK inhibitor.1
RINVOQ 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). RINVOQ may be used as monotherapy or in combination with methotrexate.1
RINVOQ’s safety profile has been established across a robust clinical trial platform involving more than 4,000 patients and more than 3,400 patient-years of exposure*2
*Patients received RINVOQ 15mg and in certain studies upadacitinib 30mg.2 The approved dose of RINVOQ is 15mg QD. Upadacitinib 30mg QD is not an approved dose,1 therefore results including this dose are not included in this portal.
QD, Once Daily.
WELL-CHARACTERISED safety profile across multiple patient populations in 5 Phase 3 studies3
Integrated safety analysis3
In patients with moderate to severe active RA.1,3
Integrated safety analysis of 5 Phase 3 studies, which included SELECT-NEXT, -BEYOND, -MONOTHERAPY, -COMPARE and –EARLY.3
*MTX pooled includes patients on MTX monotherapy censored at time of rescue to combination therapy (either to RINVOQ + MTX or addition of csDMARDs).3
†MACE was defined as cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.3
‡VTE was defined as deep vein thrombosis and pulmonary embolism.3
§Deaths included non–treatment-emergent deaths (3 on RINVOQ and 1 on adalimumab).3
csDMARD, conventional synthetic Disease-Modifying Anti-Rheumatic Drug; EOW, Every Other Week; MTX, Methotrexate; PY, Patient-Year; QD, Once Daily; RA, Rheumatoid Arthritis.
Contraindications1
- Hypersensitivity to the active substance or to any of the excipients
- Active tuberculosis (TB) or active serious infections
- Severe hepatic impairment
- Pregnancy
Summary of the RINVOQ safety profile
The most commonly reported adverse drug reactions are upper respiratory tract infections (13.5%), nausea (3.5%), blood creatine phosphokinase (CPK) increased (2.5%), and cough (2.2%). The most common serious adverse reactions were serious infections.1
Adverse drug reactions1
A total of 2,630 RA patients received at least one dose of RINVOQ 15mg QD in the 5 Phase 3 studies.2 Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
*URTI includes: acute sinusitis, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, sinusitis, tonsillitis, viral upper respiratory tract infection.1
†Herpes simplex includes oral herpes.1
ALT, Alanine Aminotransferase; AST, Aspartate Aminotransferase; CPK, Creatine Phosphokinase; QD, Once Daily; RA, Rheumatoid Arthritis; URTI, Upper Respiratory Tract Infections.
Special Warnings and Precautions1
- Serious infections: Serious and sometimes fatal infections have been reported in patients receiving RINVOQ. RINVOQ should not be initiated in patients with active, serious infection, including localised infections. Consider the risks and benefits of treatment prior to initiating RINVOQ in patients with: chronic or recurrent infection, history of serious or opportunistic infection, those who have been exposed to tuberculosis, those who have resided or travelled in areas of endemic tuberculosis or endemic mycoses, or those with underlying conditions that may predispose patients to infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with RINVOQ. Treatment should be interrupted if a patient develops a serious or opportunistic infection and until the infection is controlled. As there is a higher incidence of infections in the elderly ≥75 years of age, caution should be used when treating this population
- Tuberculosis (TB): Patients should be screened for TB before starting on RINVOQ. RINVOQ should not be given to patients with active TB. Anti-TB therapy should be considered prior to initiation of RINVOQ in patients with previously untreated latent TB, or in patients with risk factors for TB infection. Monitor patients for the development of signs and symptoms of TB, including patients who tested negative for latent TB infection prior to initiating therapy
- Viral reactivation: Screening for viral hepatitis and monitoring for reactivation should be performed before starting and during therapy with RINVOQ. lf a patient develops herpes zoster, consider interruption of RINVOQ therapy until the episode resolves. If hepatitis B virus DNA is detected while receiving RINVOQ, a liver specialist should be consulted
- Venous thromboembolism: RINVOQ should be used with caution in patients at high risk for deep venous thrombosis (DVT)/pulmonary embolism (PE). lf clinical features of DVT/PE occur, RINVOQ treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment. Risk factors that should be considered in determining the patient’s risk for DVT/PE include older age, obesity, a medical history of DVT/PE, patients undergoing major surgery, and prolonged immobilisation
- Malignancy: Malignancies were observed in clinical studies. Periodic skin examination is recommended for patients who are at increased risk for skin cancer
- Cardiovascular risk: Patients treated with RINVOQ should have risk factors (e.g., hypertension, hyperlipidaemia) managed as part of usual standard of care
- Lipids: RINVOQ treatment was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined
- Vaccinations: Use of live, attenuated vaccines during or immediately prior to RINVOQ therapy is not recommended. Prior to initiating RINVOQ, it is recommended that patients be brought up to date with all immunisations, including prophylactic zoster vaccinations, in agreement with current immunisation guidelines
- lmmunosuppressive medicinal products: Combination with other potent immunosuppressants such as azathioprine, ciclosporin, tacrolimus, and bDMARDs or other JAK inhibitors has not been evaluated in clinical studies and is not recommended as a risk of additive immunosuppression cannot be excluded
- Hepatic transaminase elevations: Monitor liver enzymes at baseline and thereafter according to routine patient management. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. In such cases therapy should be interrupted until this diagnosis is excluded
Monitoring requirements1
Treatment with RINVOQ should not be initiated if:
- Absolute neutrophil count <1,000 cells/mm3*
- Absolute lymphocyte count <500 cells/mm3*
- Hemoglobin levels <8g/dL*
*Treatment may be initiated or restarted after levels return above specified values.1
Laboratory measures and monitoring guidance1
Special populations1
Elderly
No dose adjustment is required in patients aged 65 years and older. There are limited data in patients aged 75 years and older.
Renal impairment
No dose adjustment is required in patients with mild or moderate renal impairment. There are limited data on the use of RINVOQ in subjects with severe renal impairment. RINVOQ should be used with caution in patients with severe renal impairment. The use of RINVOQ has not been studied in subjects with end-stage renal disease.
Hepatic impairment
No dose adjustment is required in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. RINVOQ should not be used in patients with severe (Child Pugh C) hepatic impairment.
Paediatric population
The safety and efficacy of RINVOQ in children and adolescents aged 0 to less than 18 years have not yet been established. No data are available.
References
- RINVOQ (upadacitinib) Summary of Product Characteristics, available at www.medicines.ie.
- European Medicines Agency. RINVOQ: EPAR - Public Assessment Report. EMA/608624/2019 Corr. 1. Available from: https://www.ema.europa.eu/en/documents/assessment-report/rinvoq-epar-public-assessment-report_en.pdf [Accessed June 2020].
- Cohen S, van Vollenhoven R, Winthrop K, et al. Safety Profile of Upadacitinib in Rheumatoid Arthritis: Integrated Analysis from the SELECT Phase 3 Clinical Program [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). Available from: https://acrabstracts.org/abstract/safety-profile-of-upadacitinib-in-rheumatoid-arthritis-integrated-analysis-from-the-select-phase-3-clinical-program/ [Accessed June 2020].
Date of preparation: June 2020 IE-RNQR-200011
RINVOQ HUMIRA – Legal Category: POM (S1A).
Further information is available on request from AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24, Ireland.
▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, website: www.hpra.ie
