RINVOQ is an oral selective and reversible JAK inhibitor 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. RINVOQ may be used as monotherapy or in combination with methotrexate.1
A Phase 3 study and open-label extension investigating the efficacy and safety of RINVOQ compared with placebo for the treatment of active PsA in patients with an inadequate response to biologic DMARDs1,2
The approved dose of RINVOQ in active PsA is 15 mg QD. Upadacitinib 30 mg QD is not an approved dose in PsA.
Stable treatment of NSAIDs, corticosteroids, and ≤2 non-biologic DMARDs were permitted, but not required.
Starting at Week 16, patients who did not achieve ≥20% improvement in tender and swollen joint counts compared to baseline at Weeks 12 and 16 had background medication(s) adjusted or initiated. Starting at Week 36, patients who did not achieve ≥20% improvement in tender and swollen joint counts compared to baseline at 2 consecutive visits were discontinued from the study. All patients who completed Week 56 were eligible to remain in the extension period of the trial for up to 3 years of trial participation in total. At Week 24, all patients allocated to placebo at baseline were switched to blinded RINVOQ 15 mg QD or upadacitinib 30 mg QD regardless of clinical response.
Primary efficacy endpoint
ACR20 response for RINVOQ vs placebo at Week 12
Key ranked secondary endpoints
(RINVOQ vs placebo)
- Change from baseline in HAQ-DI at Week 12
- Change from baseline in FACIT-F at Week 12
- Change from baseline in SF-36 PCS at Week 12
- Proportion of subjects achieving a slGA of Psoriasis of 0 or 1 and at least a 2-point improvement from baseline at Week 16
- PASI 75 response at Week 16
- Change from baseline in SAPS at Week 16
- Proportion of subjects achieving MDA at Week 24
Other key secondary endpoints
- ACR50/70 at Week 12†
- ACR20 at Week 2†
Safety assessments
Data for treatment-emergent adverse events and laboratory assessments were collected during the study. Treatment-emergent adverse events were defined as adverse events that began or worsened in severity after the first dose of study medication through 30 days after the last dose.
†Not tested for significance/not multiplicity-controlled; no clinical inferences can be drawn from these data.
- ≥18 years old at screening
- Clinical diagnosis of PsA with symptom onset ≥6 months prior to screening and fulfillment of the CASPAR criteria
- Active disease at baseline defined as ≥3 tender joints and ≥3 swollen joints
- Diagnosis of active plaque psoriasis or documented history of plaque psoriasis
- Inadequate response or intolerance to treatment with at least one biologic DMARD*
- Currently taking ≤2 non-biologic DMARDs
*Lack of efficacy after ≥12 weeks of therapy; intolerance or contraindication as defined by investigator.
- Prior exposure to any JAK inhibitor
Baseline demographics, disease characteristics, and disease severity were generally balanced across treatment arms.
ACR20/50/70: American College of Rheumatology 20%/50%/70% improvement in both tender and swollen joint counts, plus three of the following: patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant (high sensitivity C-reactive protein); CASPAR: Classification Criteria for Psoriatic Arthritis; DMARD: disease-modifying antirheumatic drug; EOW: every other week; FACIT-F: Functional Assessment of Chronic Illness Therapy-fatigue; HAQ-DI: Health Assessment Questionnaire Disability Index; JAK: Janus kinase; MDA: minimal disease activity; MTX: methotrexate; OLE: open-label extension; PASI 75: At least 75% improvement in Psoriasis Area and Severity Index; QD: once daily; SAPS: self-assessment of psoriasis symptoms; SF-36 PCS: short form (36) health survey (SF-36) physical component summary; sIGA: static Investigator’s global assessment; SJC: swollen joint count; TJC: tender joint count; ULN: upper limit of normal.
In patients with active PsA and an inadequate response to biologic DMARDs
Significantly greater ACR20 joint symptom improvement vs placebo at Week 12 in bDMARD-IR patients
SELECT-PsA 2: ACR20/50/70 response rates at Week 12 (NRI)1,2
*P≤0.001 vs placebo, statistically significant in the multiplicity-controlled analysis.1
†Nominal P≤0.05 vs placebo, no clinical inferences can be drawn.2
ACR20 for RINVOQ vs placebo at Week 12 was the primary multiplicity-controlled endpoint. Missing data were handled using NRI.
In patients with active PsA and an inadequate response to biologic DMARDs
ACR20 response over time in bDMARD-IR patients
SELECT-PsA 2: ACR20 response rates through Week 56 (NRI)3
At Week 24, all patients randomized to placebo were switched to RINVOQ 15 mg or upadacitinib 30 mg QD in a blinded manner. Upadacitinib 30 mg QD results not provided since 30 mg is not an approved dose in PsA. All data shown are from Week 56 of SELECT-PsA 2 and may include differences when compared with the primary Week 24 analysis. Missing data were handled using NRI.
DATA LIMITATIONS: Data not labeled as a ranked primary or secondary endpoint were prespecified, however they were not ranked or controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
In patients with active PsA and an inadequate response to biologic DMARDs
ACR50 response over time in bDMARD-IR patients
SELECT-PsA 2: ACR50 response rates through Week 56 (NRI)3
At Week 24, all patients randomized to placebo were switched to RINVOQ 15 mg or upadacitinib 30 mg QD in a blinded manner. Upadacitinib 30 mg QD results not provided since 30 mg is not an approved dose in PsA. All data shown are from Week 56 of SELECT-PsA 2 and may include differences when compared with the primary Week 24 analysis. Missing data were handled using NRI.
DATA LIMITATIONS: Data not labeled as a ranked primary or secondary endpoint were prespecified, however they were not ranked or controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
In patients with active PsA and an inadequate response to biologic DMARDs
ACR70 response over time in bDMARD-IR patients
SELECT-PsA 2: ACR70 response rates through Week 56 (NRI)3
At Week 24, all patients randomized to placebo were switched to RINVOQ 15 mg or upadacitinib 30 mg QD in a blinded manner. Upadacitinib 30 mg QD results not provided since 30 mg is not an approved dose in PsA. All data shown are from Week 56 of SELECT-PsA 2 and may include differences when compared with the primary Week 24 analysis. Missing data were handled using NRI.
DATA LIMITATIONS: Data not labeled as a ranked primary or secondary endpoint were prespecified, however they were not ranked or controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
95% confidence intervals are displayed as error bars in the chart.
ACR20/50/70: American College of Rheumatology 20%/50%/70% improvement in both tender and swollen joint counts, plus three of the following: patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant (high sensitivity C-reactive protein); csDMARD: conventional synthetic disease-modifying antirheumatic drug; NRI: nonresponder imputation; QD: once daily.
In patients with active PsA and an inadequate response to biologic DMARDs
Efficacy for bDMARD-IR patients with skin manifestations at Week 16
SELECT-PsA 2: PASI 75/90/100 response rates at Week 16 (NRI)1,2
NOTE TO AFFILIATES: As PASI 100 data is not listed in the SmPC but is published, please assess its inclusion through Week 56 according to local policy and regulations.
In subjects with ≥3% BSA psoriasis at baseline. Missing data were handled using NRI.
*P≤0.001 vs placebo, statistically significant in the multiplicity-controlled analysis.1
†Nominal P≤0.05 vs placebo, no clinical inferences can be drawn.2
In patients with active PsA and an inadequate response to biologic DMARDs
PASI 75 response over time in bDMARD-IR patients
SELECT-PsA 2: PASI 75 response rates through Week 56 (NRI)3
In subjects with ≥3% BSA psoriasis at baseline.
At Week 24, all patients randomized to placebo were switched to RINVOQ 15 mg or upadacitinib 30 mg QD in a blinded manner. Upadacitinib 30 mg QD results not provided since 30 mg is not an approved dose in PsA. All data shown are from Week 56 of SELECT-PsA 2 and may include differences when compared with the primary Week 24 analysis. Missing data were handled using NRI.
In patients with active PsA and an inadequate response to biologic DMARDs
PASI 90 response over time in bDMARD-IR patients
SELECT-PsA 2: PASI 90 response rates through Week 56 (NRI)3
In subjects with ≥3% BSA psoriasis at baseline.
At Week 24, all patients randomized to placebo were switched to RINVOQ 15 mg or upadacitinib 30 mg QD in a blinded manner. Upadacitinib 30 mg QD results not provided since 30 mg is not an approved dose in PsA. All data shown are from Week 56 of SELECT-PsA 2 and may include differences when compared with the primary Week 24 analysis. Missing data were handled using NRI.
In patients with active PsA and an inadequate response to biologic DMARDs
PASI 100 response over time in bDMARD-IR patients
SELECT-PsA 2: PASI 100 response rates through Week 56 (NRI)3
In subjects with ≥3% BSA psoriasis at baseline.
At Week 24, all patients randomized to placebo were switched to RINVOQ 15 mg or upadacitinib 30 mg QD in a blinded manner. Upadacitinib 30 mg QD results not provided since 30 mg not an approved dose in PsA. All data shown are from Week 56 of SELECT-PsA 2 and may include differences when compared with the primary Week 24 analysis. Missing data were handled using NRI.
DATA LIMITATIONS: Data not labeled as a ranked primary or secondary endpoint were prespecified, however they were not ranked or controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
95% confidence intervals are displayed as error bars in the chart.
bDMARD: biologic diseasemodifying antirheumatic drug; BSA: body surface area; csDMARD: conventional synthetic disease-modifying antirheumatic drug; NRI: nonresponder; PASI 75/90/100: at least 75%/90%/100% improvement in Psoriasis Area and Severity Index; QD: once-daily.
In patients with active PsA and an inadequate response to biologic DMARDs
Significantly more bDMARD-IR patients treated with RINVOQ achieved minimal disease activity vs placebo at Week 24
SELECT-PsA 2: Minimal disease activity† at Week 24 (NRI)1,2
*P≤0.001 vs placebo, statistically significant in the multiplicity-controlled analysis.1
†Minimal disease activity (MDA) is achieved when meeting 5 of 7 criteria:2,4
- Tender joint count ≤1
- Swollen joint count ≤1
- PASI ≤1 or BSA-Ps ≤3%
- Patient pain NRS ≤1.5
- Patient Global Disease Activity NRS ≤2
- HAQ-DI ≤0.5
- Tender entheseal points (LEI) ≤1
95% confidence intervals are displayed as error bars in the chart. Missing data were handled using NRI.
BSA-Ps: body surface area with psoriasis; bDMARD: biologic disease-modifying antirheumatic drug; csDMARD: conventional synthetic disease-modifying antirheumatic drug; HAQ-DI: Health Assessment Questionnaire Disability Index; LEI: Leeds Enthesitis Index; NRI: nonresponder imputation; NRS: numeric rating scale; PASI: Psoriasis Area and Severity Index; QD: once daily.
In patients with active PsA and an inadequate response to biologic DMARDs
Minimal disease activity over time in bDMARD-IR patients
SELECT-PsA 2: Minimal disease activity through Week 56 (NRI)3
At Week 24, all patients randomized to placebo were switched to RINVOQ 15 mg or upadacitinib 30 mg QD in a blinded manner. Upadacitinib 30 mg QD results not provided since 30 mg is not an approved dose in PsA. All data shown are from the Week 56 data cut of SELECT-PsA 2 and may include differences when compared with the primary Week 24 analysis.
95% confidence intervals are displayed as error bars in the chart. Missing data were handled using NRI.
DATA LIMITATIONS: Data not labeled as a primary or ranked secondary endpoint were prespecified, however they were not ranked or controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BSA-Ps: body surface area with psoriasis; bDMARD: biologic disease-modifying antirheumatic drug; csDMARD: conventional synthetic disease-modifying antirheumatic drug; HAQ-DI: Health Assessment Questionnaire Disability Index; LEI: Leeds Enthesitis Index; NRI: nonresponder imputation; NRS: numeric rating scale; PASI: Psoriasis Area and Severity Index; QD: once daily.
The safety profile of RINVOQ in PsA was consistent with previously reported results in RA1-3*
SELECT-PsA 2: Adverse events in bDMARD-IR patients through Week 24 and the Week 56 data cut2,3††
Week 24 TEAEs, n (%)2
Week 56 data cut events/100 PYs‡ (95% CI)3
Most common adverse events: In SELECT-PsA 2, the most common AEs at Week 24 and the Week 56 data cut were upper respiratory tract infection and nasopharyngitis.2,3#
For the safety analysis at the Week 56 data cut, the RINVOQ 15-mg group included patients who were originally randomized to placebo and switched to RINVOQ 15 mg at Week 24.
Adverse events leading to discontinuation of study drug occurred in 5.2% of patients in the placebo group and 7.1% in the RINVOQ 15-mg-QD group through Week 242 and in 10.0% in the RINVOQ 15-mg-QD group at the Week 56 data cut.3
*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.1
†In the RINVOQ 15 mg QD arm, 1 event of treatment-emergent lymphocyte morphology abnormal was identified; per the investigator, no further diagnosis was made.
‡At the Week 56 data cut, NMSC, malignancy other than NMSC, MACE, and VTEs were reported as exposure-adjusted incidence rates (EAIR). All other adverse events at the Week 56 data cut were reported as exposure-adjusted event rates (EAER).
§Four cases of basal cell carcinoma and 1 case of squamous cell carcinoma of the skin in the RINVOQ 15-mg group.
||Two cases of prostate cancer and single cases of malignant melanoma, ovarian cancer, and rectal cancer in the RINVOQ 15-mg group.
¶Two events of treatment-emergent abnormal lymphocyte morphology were identified in the RINVOQ 15-mg group; abnormal lymphocytes were not reported in subsequent laboratory testing.
#Hemoglobin: Grade 3 (<80 g/dL); neutrophils: Grade 3 (0.5–<1.0 x 109/L), Grade 4 (<0.5 x 109/L); lymphocytes: Grade 3 (0.2–<0.5 x 109/L), Grade 4 (<0.2 x 109/L); alanine aminotransferase and aspartate aminotransferase: Grade 3 (>5.0–20.0xULN), Grade 4 (>20.0xULN); creatinine: Grade 3 (>3.0–6.0xULN or >3.0xbaseline), Grade 4 (>6.0xULN); creatine phosphokinase: Grade 3 (>5.0–10xULN), Grade 4 (>10.0xULN).
**Treatment-emergent AEs reported in ≥5% of patients in any treatment arm through Week 24.
††Some patients had longer than 56 weeks of exposure at this data cut.
AE: adverse event; MACE: major adverse cardiovascular event; NMSC: nonmelanoma skin cancer; QD: once daily; VTE: venous thromboembolic event.
RINVOQ Important Safety Information1
Contraindications
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.
Special warnings and precautions for use
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 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. 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. 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. 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.
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, and 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) 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.
Adverse reactions
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 (ALT) increased, bronchitis, nausea, cough, aspartate transaminase (AST) increased, and hypercholesterolemia. The most common serious adverse reactions were serious infections.
The safety profile of upadacitinib with long term treatment was generally similar to the safety profile during the placebo-controlled period across indications.
Overall, the safety profile observed in patients with psoriatic arthritis or active ankylosing spondylitis treated with upadacitinib 15 mg was consistent with the safety profile observed in patients with RA.
This is not a complete summary of all safety information.
Please see the RINVOQ Summary of Product Characteristics for complete prescribing information.
[Insert local HUMIRA Important Safety Information]
Please see the HUMIRA Summary of Product Characteristics for complete prescribing information.
NOTE TO AFFILIATES: Consult local MRL regarding adding a link to the adalimumab SmPC in the main navigation area.
You may also be interested in
I want to receive more information
via a product specialist.
I have a question for
Medical Information.
- RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co. KG.
- Mease PJ, Lertratanakul A, Anderson JK, et al. Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2. Ann Rheum Dis. 2020;80(3):312-320. doi:10.1136/annrheumdis-2020-218870
- Mease PJ, Lertratanakul A, Papp KA, et al. Upadacitinib in patients with psoriatic arthritis and inadequate response to biologics: 56-week data from the randomized controlled Phase 3 SELECT-PsA 2 study [published online April 28, 2021]. Rheumatol Ther. doi:10.1007/s40744-021-00305-z
- Coates LC, Fransen J, Helliwell PS. Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment. Ann Rheum Dis. 2010;69(1):48-53. doi:10.1136/ard.2008.102053