RINVOQ is an oral selective and reversible JAK inhibitor 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.
RINVOQ safety profile: Well-characterized in 5 Phase 3 studies
Integrated safety analysis across multiple patient populations1
Five pivotal randomized, double-blind, controlled Phase 3 trials of RINVOQ were included in the integrated safety analyses. Placebo data were pooled from 3 placebo-controlled studies with exposures of up to 14 weeks (SELECT-NEXT and SELECT-BEYOND: up to 12 weeks; SELECT-COMPARE: up to 14 weeks). MTX data were pooled from 2 MTX-controlled studies (SELECT-EARLY and SELECT-MONOTHERAPY) with mean exposure of 36 weeks, including a maximum of 14 weeks of MTX treatment in SELECT-MONOTHERAPY. Originator adalimumab data were derived from 1 adalimumab-controlled study (SELECT-COMPARE) with mean exposure of 42 weeks. The RINVOQ 15 mg data were pooled from the above 5 studies with a mean exposure of 53 weeks. A total of 589 (22%) patients received RINVOQ for ≥72 weeks. Patients who switched from placebo, adalimumab, or MTX to RINVOQ were included in the RINVOQ analysis set from the start of RINVOQ, while those who switched from RINVOQ to adalimumab (SELECT-COMPARE) were included in the adalimumab data set from the start of adalimumab. All deaths and cardiovascular events across the clinical program were adjudicated by a blinded external cardiac adjudication committee. The most commonly reported adverse events in the RINVOQ 15 mg pooled group were upper respiratory tract infections, nasopharyngitis, and urinary tract infections.
*MTX pooled includes patients on MTX monotherapy censored at time of switch/addition of RINVOQ.
†MACE was defined as cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.
‡VTE was defined as deep vein thrombosis and pulmonary embolism.
§Deaths included non–treatment-emergent deaths (3 on RINVOQ and 1 on adalimumab).
MTX: methotrexate; PYs: patient years.
Contraindications
- 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 (ADRs) 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.2
Adverse drug reactions2
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
For more detailed safety information, please see the Important Safety Information link at the top of the page, or for complete prescribing information, the RINVOQ SmPC.
*URTI includes: acute sinusitis, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, sinusitis, tonsillitis, viral upper respiratory tract infection.
†Herpes simplex includes oral herpes.
Special Warnings and Precautions2
- Serious infections: RINVOQ should not be initiated in patients with an active, serious infection, including localized infections. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with RINVOQ. If a patient develops a serious or opportunistic infection, RINVOQ should be interrupted.
- Tuberculosis: Patients should be screened for tuberculosis (TB) before starting RINVOQ. Treatment should not be initiated in 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 treatment with RINVOQ. If 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.
- Nonmelanoma skin cancer: Periodic skin examination is recommended for patients who are at increased risk for skin cancer.
- Vaccinations: Use of live, attenuated vaccines during or immediately prior to RINVOQ treatment is not recommended. Prior to initiating RINVOQ, it is recommended that patients be brought up to date with all immunizations, including prophylactic zoster vaccinations, in agreement with current immunization guidelines.
- Venous thromboembolism: RINVOQ should be used with caution in patients at high risk for deep venous thrombosis (DVT)/pulmonary embolism (PE). If clinical features of DVT/PE occur, RINVOQ treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment.
Monitoring requirements
Treatment with RINVOQ should not be initiated if:2
- Absolute neutrophil count <1,000 cells/mm3*
- Absolute lymphocyte count <500 cells/mm3*
- Hemoglobin <8 g/dL*
Laboratory measures and monitoring guidance2
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 upadacitinib has not been studied in subjects with end-stage renal disease.2
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.2
Pediatric
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.
*Treatment may be initiated or restarted after levels return above specified values.
Safety Information2
RINVOQ 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.
Use in combination with other potent immunosuppressants is not recommended.
Serious and sometimes fatal infections have been reported in patients receiving upadacitinib. The most frequent serious infections reported included pneumonia and 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. Prior to initiating upadacitinib, consider the risks and benefits of treatment in patients with chronic or recurrent infection or with a history of a serious or opportunistic infection, in patients who have been exposed to TB or have resided or traveled in areas of endemic TB or endemic mycoses, and in patients with underlying conditions that may predispose them to infection. Upadacitinib therapy should be interrupted if a patient develops a serious or opportunistic infection. As there is a higher incidence of infections in patients ≥75 years of age, caution should be used when treating this population.
Patients should be screened for TB before starting upadacitinib therapy. Anti-TB therapy should be considered prior to initiation of upadacitinib in patients with previously untreated latent TB or in patients with risk factors for TB infection.
Viral reactivation, including cases of herpes zoster, were reported in clinical studies. Consider interruption of therapy if a patient develops herpes zoster until the episode resolves. Screening for viral hepatitis and monitoring for reactivation should be performed before starting and during therapy with upadacitinib.
The use of live, attenuated vaccines during or immediately prior to therapy is not recommended. It is recommended that patients be brought up to date with all immunizations, including prophylactic zoster vaccinations, prior to initiating upadacitinib, in agreement with current immunization guidelines.
The risk of malignancies, including lymphoma is increased in patients with rheumatoid arthritis (RA). Immunomodulatory medicinal products may increase the risk of malignancies, including lymphoma. The clinical data are currently limited and long-term studies are ongoing. 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. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.
Absolute neutrophil count <1000 cells/mm3, absolute lymphocyte count <500 cells/mm3, or hemoglobin levels <8 g/dL were reported in ≤1% of patients in clinical trials. Treatment should not be initiated, or should be temporarily interrupted, in patients with these hematological abnormalities observed during routine patient management.
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.
Upadacitinib 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.
Treatment with upadacitinib was associated with an increased incidence of liver enzyme elevation compared to placebo. If increases in ALT or AST are observed during routine patient management and drug-induced liver injury is suspected, upadacitinib therapy should be interrupted until this diagnosis is excluded.
Events of deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAK inhibitors, including upadacitinib. Upadacitinib should be used with caution in patients at high risk for DVT/PE. 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 immobilization. If clinical features of DVT/PE occur, upadacitinib treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment.
The most commonly reported adverse drug reactions are upper respiratory tract infections (13.5%), nausea (3.5%), increased blood creatine phosphokinase (2.5%), and cough (2.2%). The most common serious adverse reactions were serious infections.
Please see the RINVOQ Summary of Product Characteristics for complete Prescribing Information.
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References
- Cohen SB, van Vollenhoven R, Winthrop K, et al. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT Phase 3 clinical program. Poster presented at: European Congress of Rheumatology; June 12–15, 2019; Madrid, Spain.
- RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co. KG; [MM,YYYY].