Overview of the RINVOQ (upadacitinib) PsA, AS and nr-axSpA clinical study programmes1-8
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SELECT-PsA 11,2 | SELECT-PsA 23,4 | SELECT-AXIS 15,6 | SELECT-AXIS 2 | SELECT-AXIS 2 | |
Indication | PsA | PsA | AS | AS | nr-axSpA |
Previous bDMARD status | bDMARD naive | Intolerance/Inadequate | NSAID-IR | Intolerance/Inadequate | bDMARD naïve & Intolerance/Inadequate response to bDMARD |
Active comparator | Adalimumab | ̶ | ̶ | ̶ | ̶ |
Duration of period 1 | 24 weeks | 24 weeks | 14 weeks | 14 weeks | 14 weeks |
Duration of OLE | 232 weeks | 128 weeks | 90 weeks | 90 weeks | 90 weeks |
Number of RINVOQ 15 mg QD patients | 430 | 210 | 93 | 211 | 156 |
Study designs
SELECT-PsA 1
PRIMARY ENDPOINT2
ACR20 response for RINVOQ (upadacitinib) vs placebo at Week 12
STUDY DESIGN1,2
KEY INCLUSION CRITERIA2
► Age ≥18 years
► 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
► Presence of either ≥1 erosion on x-ray as determined by central imaging review or hs-CRP>ULN
► Had historic or current plaque psoriasis
► Inadequate response or intolerance to treatment with at least 1 non-biologic DMARD and on ≤2 non-biologic DMARDs
KEY EXCLUSION CRITERIA2
► Prior JAK inhibitor
► Exposure to any biologic DMARD
STATISTICAL ANALYSES
► Statistical analysis between arms and P-values were not reported for the 56-week data, hence no comparisons can be made1
► Statistical analysis out to Week 24 has been performed2
MULTIPLICITY-CONTROLLED SECONDARY ENDPOINTS2
RINVOQ vs placebo unless otherwise noted
► Change from baseline in HAQ-DI at Week 12
► Proportion of subjects achieving a sIGA 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 mTSS at Week 24
► Proportion of subjects achieving MDA at Week 24
► Proportion of subjects with resolution of enthesitis (LEI=0) at Week 24
► ACR20 response rate at Week 12 (non-inferiority vs adalimumab)
► Change from baseline in SF-36 at Week 12
► Change from baseline in FACIT-F at Week 12
► ACR20 response rate at Week 12 (superiority vs adalimumab)**
► Proportion of subjects with resolution of dactylitis (LDI=0) at Week 24δ
► Change from baseline in patient’s assessment of pain NRS at Week 12 (superiority vs adalimumab)δ
► Change from baseline in HAQ-DI at Week 12 (superiority vs adalimumab)δ
► Change from baseline in SAPS at Week 16δ
NRS, numerical rating scale.
**Superiority of RINVOQ 15 mg QD vs adalimumab 40 mg EOW could not be demonstrated, which prevented the testing of significance for secondary endpoints lower in the testing hierarchy. δNot tested for significance. #Not multiplicity controlled.
SELECT-PsA 2
PRIMARY ENDPOINT3
Proportion of patients achieving an ACR20 response at Week 12 for RINVOQ (upadacitinib) 15 mg QD vs placebo
STUDY DESIGN3,4
KEY INCLUSION CRITERIA4
► Adults (≥18 years) with active PsA, had a diagnosis of PsA with symptom onset for ≥6 months, fulfilled the CASPAR and had historical or current plaque psoriasis
► Had ≥3 swollen joints (of 66) and ≥3 tender joints (of 68) at screening and at baseline
► Inadequate response or intolerance to at least 1 biologic DMARD
KEY EXCLUSION CRITERIA4
► Previous exposure to a JAK inhibitor
► History of fibromyalgia, arthritis with onset prior to age 17 or inflammatory joint disease other than PsA
STATISTICAL ANALYSES
► P-values were not reported in the 56-week data, hence no comparisons can be made3
► Statistical analysis out to Week 24 has been reported4
MULTIPLICITY-CONTROLLED SECONDARY ENDPOINTS4
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 score at Week 12
► Proportion of patients achieving sIGA response of 0 or 1 and at least 2-point improvement from baseline at Week 16
► PASI 75 response at Week 16
► Change from baseline in SAPS Questionnaire at Week 16
► Proportion of patients achieving MDA at Week 24
SELECT-AXIS 1
PRIMARY ENDPOINT6
ASAS40 response for RINVOQ (upadacitinib) vs placebo at Week 14
STUDY DESIGN5,6
KEY INCLUSION CRITERIA6
► Age ≥18 years
► Active AS defined as meeting the modified New York criteria for ankylosing spondylitis based on central reading of radiographs of the sacroiliac joints
► BASDAI score ≥4 at screening and baseline
► Inadequate response to ≥2 NSAIDs or intolerance to/contraindication for NSAIDs
KEY EXCLUSION CRITERIA6
► Previous exposure to any JAK inhibitor or any biologic therapy with a potential effect on spondyloarthritis
► Extra-articular manifestations if clinically unstable in last 30 days
► Total spine ankylosis
MULTIPLICITY-CONTROLLED SECONDARY ENDPOINTS6
RINVOQ vs placebo at Week 14
► Change from baseline in ASDAS-CRP
► Change from baseline in SPARCC-MRI spine score
► Proportion of patients achieving BASDAI50
► Proportion of patients achieving ASAS partial remission
► Change from baseline in BASFI
► Change from baseline in ASQoL
► Change from baseline in BASMI
► Change from baseline in MASES
► Change from baseline in WPAI
► Change from baseline in ASAS Health Index (not tested for statistical significance)
STATISTICAL ANALYSES
► Statistical analysis between arms and P-values was not reported in the 104-week data, hence no comparisons can be made5
► Statistical analysis out to Week 14 was performed6
► The multiplicity-controlled secondary endpoints were tested in a sequential manner, inclusive of the group of endpoints assessed by the Hochberg procedure6
SELECT-AXIS 2
PRIMARY ENDPOINT7
ASAS40 response for RINVOQ vs placebo at Week 14
STUDY DESIGN7
KEY INCLUSION CRITERIA7
► Adults (≥18 years) who met the modified New York criteria for ankylosing spondylitis by central radiology review of SI joint radiographs
► BASDAI ≥4 and patient’s assessment of Total Back Pain score ≥4 based on a 0-10 NRS at screening and baseline visits
► Inadequate response, intolerance or contraindication to at least 2 NSAIDs
► Inadequate response to bDMARD therapy* defined as patients who discontinued bDMARD therapy (TNFi or IL-17i) due to lack of efficacy (after ≥12 weeks of treatment at an adequate dose) based on the investigators’ assessment or intolerance (irrespective of treatment duration)
*Prior exposure to two bDMARDs was allowed for no more than 30% of patients; among patients with prior exposure to two bDMARDs, a lack of efficacy to one bDMARD and intolerance to another was permitted, but a patient could not have a lack of efficacy to two bDMARDs.
KEY EXCLUSION CRITERIA7
► Previous exposure to any JAK inhibitor
► Total spine ankylosis defined as bridging syndesmophytes (fusion) in a total sum of ≥5 C2–T1 or T12–S1 spine segments
► Inadequate response to both a TNF inhibitor AND an IL-17 inhibitor
MULTIPLICITY-CONTROLLED SECONDARY ENDPOINTS7
RINVOQ vs placebo at Week 14
► Change from baseline in ASDAS-CRP
► Change from baseline in SPARCC-MRI spine inflammation score
► Proportion of patients achieving BASDAI50
► Proportion of patients achieving ASAS20
► Proportion of patients achieving ASDAS inactive disease
► Change from baseline in total back pain
► Change from baseline in nocturnal back pain
► Proportion of patients achieving ASDAS low disease activity
► Change from baseline in BASFI
► Proportion of patients achieving ASAS partial remission
► Change from baseline in AS QoL
► Change from baseline in ASAS Health Index
► Change from baseline in BASMI
► Change from baseline in MASES
RANDOMISATION WAS STRATIFIED BY7
► hs-CRP (≤ULN vs >ULN where ULN=2.87 mg/L)
► Class of prior bDMARD use (one TNFi, one IL-17i or two bDMARDs)
► Geographical region
NRS, numerical rating scale.
SELECT-AXIS 2 (nr-axSPA)
PRIMARY ENDPOINT
ASAS40 response for RINVOQ vs placebo at Week 14
SELECT-AXIS 2 (nr-axSPA) STUDY DESIGN8
KEY INCLUSION CRITERIA8
► Age ≥18 years
► Diagnosis of nr-axSpA based on 2009 ASAS criteria
► BASDAI score ≥4 and patient’s assessmentof total back pain score (NRS 0-10) ≥4 at screening and baseline
► ≥1 objective sign of active inflammation at screening based on MRI of the sacroiliac joints, high-sensitivity C-reactive protein greater than the upper limit of normal (ULN; 2.87 mg/L), or both
► Inadequate response to ≥2 NSAIDs or intolerance to/ contraindication for NSAIDs
► Up to 35% of enrolled patients could have inadequate response to 1 bDMARD
KEY EXCLUSION CRITERIA8
► Active AS defined as meeting the modified New York criteria for ankylosing spondylitis based on central reading of radiographs of the sacroiliac joints
► History of inflammatory arthritis (other than axial spondyloarthritis)
► Previous treatment with JAK inhibitor
MULTIPLICITY-CONTROLLED SECONDARY ENDPOINTS
RINVOQ vs placebo at Week 14
► ASDAS-CRP
►SPARCC-MRI spine score
► BASDAI50
► ASAS partial remission
► ASDAS low disease activity
► Total back pain
► Nocturnal back pain
► ASAS partial remission
► BASFI
► ASQoL
► ASAS Health Index
► ASAS20
► BASMI
► MASES
WARNING: Based on the results from a post-marketing safety study of another JAK inhibitor, RINVOQ should only be used if no suitable treatment alternatives are available in patients: Refer to Product Information. |
PBS Information
RINVOQ: Authority required. Refer to PBS Schedule for full authority information.
Please review the full Product Information (PI) before prescribing, available below.
REFERENCE: 1. McInnes IB, et al. RMD Open 2021;7:e001838. 2. McInnes IB, et al. NEJM 2021;384(13):1227-1239. 3. Mease PJ, et al. Rheumatol Ther. 2021;8:903-919. 4. Mease PJ, et al. Ann Rheum Dis. 2020;80(3):312-320. 5. van der Heijde D, et al. RMD Open. 2022;8(2):e002280. 6. van der Heijde D, et al. Lancet 2019;394:2108-2117. 7. van der Heijde D, et al. Ann Rheum Dis. 2022; doi: 10.1136/annrheumdis-2022-222608. 8. Deodhar A, et al. Lancet 2022;400:369-379.
AU-RNQR-220207. July 2023