RINVOQ is not approved for the treatment of MTX-naive patients
SELECT-EARLY: Study design
A Phase 3 study investigating the efficacy and safety of RINVOQ monotherapy compared with MTX in MTX-naive patients with moderately to severely active RA1,2
Rescue therapy from Weeks 12–24: In patients with <20% improvement in TJC and SJC at 2 consecutive visits, background medications were optimized.
*Rescue protocol from Week 26: group 1 if CDAI ≤2.8, patients continued their original study drug; group 2 if ≥20% improvement from baseline in tender joint count (TJC), and swollen joint count (SJC), but CDAI >2.8, background medications were optimized; group 3 if <20% improvement from baseline in TJC and SJC, and CDAI >2.8, RINVOQ 15 mg or upadacitinib 30 mg were added by rerandomization according to 1:1 ratio for those initially randomized to MTX, and MTX was added for those initially randomized to RINVOQ 15 mg or upadacitinib 30 mg.
†Study drug assignments remain the same in the blinded extension while allowing initiation of, or change in, background RA medication(s) as per local label.
RINVOQ 15 mg and upadacitinib 30 mg vs MTX for DAS28 (CRP) <2.6 at Week 24 (EMA) or ACR50 at Week 12 (FDA)
Adverse events, serious adverse events, adverse event of special interest (e.g., serious infections, opportunistic infections, MACEs, VTEs, malignancies)
- Patients ≥18 years of age were eligible to participate.
- Diagnosis of RA for ≥6 weeks fulfilling the 2010 ACR/EULAR classification for RA with active disease (at least 6 swollen joints out of 66, at least 6 tender joints out of 68, and hsCRP ≥5 mg/L) and ≥1 erosion on x-ray OR positive for both RF and ACCP.
- Patients were naive to MTX or received no more than 3 weekly MTX doses and completed a 4-week MTX washout.
- No prior intolerance to MTX, or no prior exposure to a JAK inhibitor or bDMARD.
The approved dose of RINVOQ is 15 mg once daily. Upadacitinib 30 mg is not an approved dose.
ACCP: anti-cyclic citrullinated protein; ACR: American College of Rheumatology; ACR50: improvement of at least 50% in the American College of Rheumatology core criteria; bDMARD: biological disease-modifying antirheumatic drug; CDAI: Clinical Disease Activity Index; DAS28 (CRP): disease activity score with 28 joint count (C-reactive protein); EMA: European Medicines Agency; EULAR: European League Against Rheumatism; FDA: Food and Drug Administration; hsCRP: high-sensitivity C-reactive protein; JAK: Janus kinase; MACE: major adverse cardiovascular events; MTX: methotrexate; QD: once daily; RF: rheumatoid factor; SJC: swollen joint count; TJC: tender joint count; VTE: venous thromboembolic event.
RINVOQ monotherapy data
SELECT-EARLY: Remission (primary endpoint) and low disease activity at Week 24 in MTX-naive patients1,3*
*RINVOQ is not indicated for MTX-naive patients.
† P<0.001 vs MTX
DAS28 (CRP): disease activity score with 28 joint counts (C-reactive protein); MTX: methotrexate.
Joint protection with RINVOQ monotherapy
SELECT-EARLY: Inhibition of structural joint damage progression as monotherapy in MTX-naive patients* at Week 241,3
Change in mTSS for RINVOQ vs MTX at Week 24 was a ranked secondary endpoint controlled for multiplicity. All other data shown for RINVOQ vs MTX were prespecified nonranked endpoints not controlled for multiplicity; nominal P-values are provided.
*RINVOQ is not indicated for MTX-naive patients.
† P≤0.01 vs MTX
‡ P≤0.001 vs MTX
§ P≤0.05 vs MTX
||Indicates multiplicity-controlled comparison of RINVOQ vs MTX.
LS: least squares; mTSS: modified total Sharp score; MTX: methotrexate.
SELECT-EARLY: Adverse events through 24 weeks of treatment1
*Deaths: In the methotrexate group, there was 1 sudden CV death. In the RINVOQ 15 mg group, there was 1 CV death, 1 death due to metastatic malignant melanoma.
†Herpes zoster: All non-serious, 12 were single dermatome.
‡Malignancies: In the methotrexate group, there was 1 case of ovarian cancer. In the RINVOQ 15-mg group, there was 1 metastatic malignant melanoma, 1 squamous cell carcinoma of the lung, 1 uterine carcinoma in situ.
§Major adverse cardiovascular events (adjudicated): In the methotrexate group, there was 1 CV death. In the RINVOQ 15-mg group, there was 1 nonfatal MI and 1 CV death due to other CV causes.
CV: cardiovascular; GI: gastrointestinal; MI: myocardial infarction; MTX: methotrexate.
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.
- van Vollenhoven R, Takeuchi T, Pangan AL, et al. A phase 3 randomized, controlled trial comparing upadacitinib monotherapy to MTX monotherapy in MTX-naive patients with active rheumatoid arthritis. Presented at: American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting; October 19–24, 2018; Chicago, IL.
- van Vollenhoven R, Takeuchi T, Pangan AL, et al. Monotherapy with upadacitinib in MTX-naive patients with rheumatoid arthritis: results at 48 weeks from the SELECT-EARLY study. Poster presented at: European Congress of Rheumatology (EULAR); June 12–15, 2019; Madrid, Spain.
- RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co. KG; [MM,YYYY].
Date of preparation: May 2020 IE-RNQR-200014
▼ 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.