RINVOQ Axial spondylartrit (axSpA)
RINVOQ® (upadacitinib), en oral selektiv JAK-hämmare, är indicerat för behandling av:
- måttlig till svår aktiv reumatoid artrit hos vuxna patienter med otillräckligt behandlingssvar på eller intolerans mot ett eller flera DMARDs, i monoterapi eller i kombination med metotrexat.
- aktiv psoriasisartrit hos vuxna patienter med otillräckligt behandlingssvar på eller intolerans mot ett eller flera DMARDs, i monoterapi eller i kombination med metotrexat.
- vuxna patienter med aktiv icke-radiografisk axial spondylartrit med objektiva tecken på inflammation påvisat genom förhöjda nivåer av C-reaktivt protein (CRP) och/eller magnetisk resonanstomografi (MRT) och som har otillräckligt behandlingssvar på icke-steroida antiinflammatoriska läkemedel (NSAID).
- aktiv ankyloserande spondylit hos vuxna patienter med otillräckligt behandlingssvar på konventionell behandling.
Permitted concomitant medications were csDMARDs (methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine), oral glucocorticoids, NSAIDs, and analgesics.
Primary
ASAS40 response for RINVOQ vs placebo at Week 14
Secondary (RINVOQ vs placebo at Week 14)*
• Change from baseline ASDAS†
• Change from baseline in SPARCC MRI spine score†
• BASDAl 50†
• 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‡
Safety
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.
*The multiplicity-controlled secondary endpoints were tested in a sequential manner: ASDAS, SPARCC MRI spine, group of endpoints tested by Hochberg procedure (BASDAl 50, ASQoL, ASAS partial remission, BASFI, BASMI, MASES, and WPAI), and ASAS Health Index. ASAS Health Index could not be evaluated within the multiplicity-controlled sequence because some endpoints in the Hochberg procedure were not significant (NS).
†Statistically significant in multiplicity-controlled analysis.
‡Not multiplicity-controlled; nominal P<0.05 vs placebo. No clinical inferences can be drawn.
§Not multiplicity-controlled. No clinical inferences can be drawn.
ASAS: Assessment of Ankylosing Spondylitis International Society; ASDAS: Ankylosing Spondylitis Disease Activity Score; ASQoL: ankylosing spondylitis quality of life; BASDAI 50: at least 50% improvement in Bath Ankylosing Spondylitis Disease Activity Index; BASFI: Bath Ankylosing Spondylitis Functional Index; BASMI: Bath Ankylosing Spondylitis Metrology Index; MASES: Maastricht Ankylosing Spondylitis Enthesitis Score; SPARCC MRI: Spondyloarthritis Research Consortium of Canada magnetic resonance imaging; WPAI: Work Productivity and Activity Impairment; QD: once daily.
- Patients ≥18 years of age were eligible to participate
- Met the modified New York criteria for ankylosing spondylitis based on central reading of radiographs of the sacroiliac joints
- BASDAI score ≥4 at baseline
- Patient assessed back pain score ≥4 at screening and baseline
- Had inadequate response to at least 2 NSAIDs or intolerance to or contraindication for NSAIDs
- Patients with previous exposure to any JAK therapy or any biologic therapy with a potential effect on spondyloarthritis were excluded
- Patients with total spinal ankylosis were excluded from the study
Most patients were men (132 [71%]), were HLA-B27 positive (143 [76%]), and were receiving concomitant nonsteroidal anti-inflammatory drugs at baseline (152 [81%]). Baseline disease characteristics were generally balanced between the two groups.
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SELECT-AXIS 2: Studiedesign
Två fas 3 studier som utvärderar effekt och säkerhet av RINVOQ för behandling av bio-erfarna patienter med AS samt patienter med nr-axSpA1,4,5
Permitted concomittant medications were csDMARDs, oral glucocorticoids, NSAIDs.
All patients rendomized to placebo recived open-label RINVOQ 15 mg QD starting from Week 14 (bDMARD-IR) or Week 52 (nr-axSpA).
*At baseline, 77,4% had lack of effiacy to either a TNFi or IL-17i; 30,2% had intolerance; 12,9% had prior exposure but lack of efficacy to two bDMARDs.
†At baseline, 32,9% of the patients had an inadequate respons or intolerance to bDMARD therapy.
Primary
ASAS40 response for RINVOQ vs placebo at Week 14
Secondary, multiplicity-controlled (RINVOQ vs placebo at Week 14)
SELECT-AXIS 2 - bDMARD-IR AS
• Change from baseline ASDAS-CRP*
• Change from baseline in SPARCC MRI spine score*
• Proportion of patients achieving BASDAl 50*
• Proprortion of patients achieving ASAS20*
• Proprortion of patients achieving ASDAS-CRP inactive disease*
• Change from baseline in total back pain*
• Change from baseline in nocturnal back pain*
• Proprortion of patients achieving ASDAS-CRP low disease activity*
• Change from baseline in BASFI*
• Proprortion of patients achieving ASAS partial remission*
• Change from baseline in ASQoL*
• Change from baseline in ASAS Health Index*
• Change from baseline in BASMI*
• Change from baseline in MASES*
SELECT-AXIS 2 - nr-axSpA
• Change from baseline ASDAS-CRP*
• Change from baseline in SPARCC MRI joint score*
• Proportion of patients achieving BASDAl 50*
• Proprortion of patients achieving ASDAS-CRP inactive disease*
• Change from baseline in total back pain*
• Change from baseline in nocturnal back pain*
• Proprortion of patients achieving ASDAS-CRP low disease activity*
• Proprortion of patients achieving ASAS partial remission*
• Change from baseline in BASFI*
• Change from baseline in ASQoL*
• Change from baseline in ASAS Health Index*
• Proprortion of patients achieving ASAS20*
• Change from baseline in BASMI*
• Change from baseline in MASES*
Safety
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.
*Statistically significant in multiplicity-controlled analysis.
ASAS: Assessment of Ankylosing Spondylitis International Society; ASDAS: Ankylosing Spondylitis Disease Activity Score; ASQoL: ankylosing spondylitis quality of life; BASDAI 50: at least 50% improvement in Bath Ankylosing Spondylitis Disease Activity Index; BASFI: Bath Ankylosing Spondylitis Functional Index; BASMI: Bath Ankylosing Spondylitis Metrology Index; MASES: Maastricht Ankylosing Spondylitis Enthesitis Score; SPARCC MRI: Spondyloarthritis Research Consortium of Canada magnetic resonance imaging; QD: once daily.
SELECT-AXIS 2 - bDMARD-IR
- ≥18 years of age were eligible to participate
- Met 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
- Patient assessed back pain score ≥4 at screening and baseline
- Had prior exposure to bDMARD (lack of efficacy to either a TNFi or IL-17i, intolerance, or prior exposure but not lack of effiacy to 2 bDMARDs)
- Patient with previous exposure to any JAK therapy or had total spinal ankylosis were excluded
SELECT-AXIS 2 - nr-axSpA
- ≥18 years of age with active non-radiograpic axial spondyloarthritis
- Active disease as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4 and a Patient´s Assessment of Total back Pain score ≥4 based on a 0-10 numerical rating scale (NRS) at screening and baseline
- Inadequate response to at least to NSAIDs or intolerance to or contraindication for NSAIDs
- Objective signs of inflammtion indicated by elevated C-reactive protein (CRP) (defined as >upper limit of normal), and/or sacroiliitis on magnetic resonance imaging (MRI), and no definitive rediographic evidence of structural damage on sacroiliac joints
SELECT-AXIS 2 - bDMARD-IR
Patient with previous exposure to any JAK therapy or had total spinal ankylosis were excluded.
SELECT-AXIS 2 - bDMARD-IR
77,4% had lack of effiacy to either a TNFi or IL-17i; 30,2% had intolerance; 12,9% had prior exposure but lack of efficacy to two bDMARDs.
SELECT-AXIS 2 - nr-axSpA
32,9% of the patients had an inadequate respons or intolerance to bDMARD therapy.
SELECT-AXIS 1:
AS Bio-naiva2
Patienter med aktiv AS och som inte svarat på konventionell behandling.
SELECT-AXIS 2:
AS Bio-erfarna4
Patienter med aktiv AS och som inte svarat på biologisk behandling.
SELECT-AXIS 2:
nr-axSpA5
Patienter med aktiv nr-axSpA och med otillräckligt svar på minst 2 NSAID.
Behandling med RINVOQ resulterar i en högre ASAS40 respons1
SELECT-AXIS 1 och 2: ASAS40 vid vecka 14 (NRI)2,4,5
I SELECT-AXIS 1 bibehölls den högre ASAS40-responsen i 2 år1.
*P≤0,001 vs placebo, justerat för multiplicitet
ASAS40: at least 40% improvement in Assessment of Ankylosing Spondylitis International Working Group criteria; NRI: nonresponder imputation; NRI-MI: nonresponder imputation-multiple imputation QD: once daily.
Behandling med RINVOQ minskar sjukdomsaktiviteten
(mätt med ASDAS-LDA)1
SELECT-AXIS 1 och 2: ASDAS-LDA respons vid vecka 142,4,5
I SELECT-AXIS 1 bibehölls låg sjukdomsaktivitet (ASDAS-LDA) i 2 år1.
apost hoc analys av SELECT-AXIS 1, ej justerat för multiplicitet
*P≤0,001 vs placebo, justerat för multiplicitet
ASDAS-LDA: The Ankylosing Spondylitis Disease Activity Score-Low Disease Activity; QD: once daily.
Behandling med RINVOQ minskar spinal inflammation
(mätt med SPARCC-MRI spine score)1
SELECT-AXIS 1 och 2: Förändring i SPARCC MRI score från baslinjen till vecka 142,4,5
I SELECT-AXIS 1 bibehölls förbättring av inflammation som bedömdes med MRT i 2 år1.
SPARCC MRI: Spondyloarthritis Research Consortium of Canada magnetic resonance imaging.
Säkerhetprofilen för RINVOQ vid axSpA överrensstämmer med tidigare rapporterade resultat för RA1-5
SELECT-AXIS 1 - AS Bio-naiva: Biverkningar till och med vecka 14 och 641-3
The most common adverse event with RINVOQ through Week 14 was increased creatine phosphokinase.2
No serious infections, active tuberculosis, venous thromboembolic events, gastrointestinal perforation, major adverse cardiovascular events, renal dysfunction, or deaths were reported. *Cardiovascular disorder, reported as mild circulation dysregulation. †Spinal osteoarthritis, reported as moderate worsening of cervical spondylosis 4/5. ‡Dyspepsia (n=1), blood creatine phosphokinase increased (n=1), and atlantoaxial instability (n=1). §Otitis media (n=1) and myalgia (n=1). ¶Esophageal candidiasis in patient with gastro-esophageal reflux disease; study drug continued after treatment with fluconazole. ¥Including nonmelanoma skin cancer, malignancy other than nonmelanoma skin cancer, and lymphoma. #All seven hepatic disorders were based on asymptomatic alanine aminotransferase or aspartate aminotransferase increases, and none led to premature discontinuation of study drug. **All asymptomatic except for one patient in the placebo group. ††Two nonserious events of esophageal candidiasis in the same patient. ‡‡Five events in four patients; all nonserious and limited to one dermatome. ##Majority based on asymptomatic alanine aminotransferase/aspartate aminotransferase elevations; all were nonserious and none led to study drug discontinuation. §§All events were nonserious and none led to study drug discontinuation. ¥¥Squamous cell carcinoma of tongue in 61-year-old former smoker; no reasonable possibility to be study drug-related per investigator.
SELECT-AXIS 2 - AS Bio-erfarna och nr-axSpA: Biverkningar till och med vecka 141,4,5
Minimiinformation
RINVOQ® (upadacitinib), depottablett 15 mg, 30 mg, 45 mg (F), Rx, ATC-kod L04AF03 JAK-hämmare. Indikationer: måttlig till svår aktiv reumatoid artrit hos vuxna med otillräckligt behandlingssvar på eller intolerans mot ett eller flera DMARDs i monoterapi eller i kombination med metotrexat. Aktiv psoriasisartrit hos vuxna med otillräckligt behandlingssvar på eller intolerans mot ett eller flera DMARDs, i monoterapi eller i kombination med metotrexat. Axial spondylartrit: – Aktiv icke-radiografisk axial spondylartrit hos vuxna med objektiva tecken på inflammation som anges av förhöjda nivåer av CRP och/eller MRI, som har otillräckligt behandlingssvar på NSAID. – Aktiv ankyloserande spondylit (radiografisk axial spondylartrit) hos vuxna med otillräckligt behandlingssvar på konventionell behandling. Måttlig till svår atopisk dermatit hos vuxna och ungdomar 12 år och äldre vilka är aktuella för systemisk behandling. Måttlig till svår aktiv ulcerös kolit eller Crohns sjukdom hos vuxna med otillräckligt behandlingssvar, förlorat behandlingssvar eller som varit intoleranta mot konventionell behandling eller biologiska läkemedel. Kontraindikationer: Överkänslighet mot den aktiva substansen eller mot något hjälpämne. Aktiv tuberkulos (TB) eller aktiv allvarlig infektion. Gravt nedsatt leverfunktion. Graviditet. Effekter på förmågan att framföra fordon: RINVOQ kan ha en liten effekt på förmågan att framföra fordon och använda maskiner eftersom yrsel och vertigo kan inträffa under behandling. Varningar och försiktighet: RINVOQ ska endast användas om inga lämpliga behandlingsalternativ är tillgängliga för patienter: som är 65 år eller äldre; med en anamnes på aterosklerotisk hjärt-kärlsjukdom eller andra kardiovaskulära riskfaktorer (t.ex. nuvarande eller tidigare långtidsrökare); med riskfaktorer för malignitet (t.ex. nuvarande eller tidigare malignitet). RINVOQ ska inte påbörjas hos patienter med aktiva, allvarliga infektioner, inkl. lokala infektioner och TB. Virusreaktivering, inkl. fall av reaktivering av herpesvirus (t.ex. herpes zoster), har rapporterats i kliniska studier. Påbörja inte eller avbryt tillfälligt behandling om onormala lab-värden som anemi, neutropeni, lymfopeni och levertransaminaser påträffas. RINVOQ associerades med ökade lipidparametrar i kliniska studier. Divertikulit och gastrointestinal perforation har rapporteras i kliniska prövningar och från klinisk erfarenhet. Patienter med aktiv Crohns sjukdom löper ökad risk att utveckla tarmperforation. VTE har rapporterats hos patienter på RINVOQ. Hos patienter med kända VTE-riskfaktorer ska RINVOQ användas med försiktighet. Allvarliga överkänslighetsreaktioner har rapporterats med RINVOQ. Fertilitet, graviditet och amning: Fertila kvinnor ska rådas använda effektiv preventivmetod under behandling och i minst 4 veckor efter avslutad behandling. RINVOQ är kontraindicerat under graviditet och ska inte användas under amning. För ytterligare information samt priser se www.fass.se. För information: kontakta AbbVie AB, 08 684 44 600. Datum för översyn av produktresumén: 24 oktober 2024. Begränsning av läkemedelsförmån: RINVOQ subventioneras 1) när behandling med TNF-hämmare gett otillräcklig effekt eller inte är lämplig 2) för patienter med atopisk dermatit när konventionell topikal eller systemisk behandling gett otillräcklig effekt eller inte är lämplig.
SE-RNQ-220026 v 9.0 Senast uppdaterad 2024-11-20
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Referenser
- RINVOQ produktresumé
- van der Heijde D, et al. Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial. Lancet. 2019;394(10214):2108-2117. doi:10.1016/S0140-6736(19)32534-6
- Deodhar A, van der Heijde D, Sieper J, et al. Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis: 1-year results from a randomized, double-blind, placebo-controlled study with open-label extension [ACR abstract 2023]. Arthritis Rheumatol. 2020;72(suppl 10).
- van der Heijde D, et al. Efficacy and safety of upadacitinib for activ ankylosing spondylitis refractory to biological therapy: a double- blind, randomised, placebo- controlled phase 3 trial. Ann Rheum Dis 2022;0:1–9. doi:10.1136/annrheumdis-2022-222608
- Deodhar A, et al. Upadacitinib for the treatment of active non-radiographic axial spondyloarthritis (SELECT-AXIS 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2022 Jul 30;400(10349):369-379. doi: 10.1016/S0140-6736(22)01212-0.
SE-RNQ-220012 v 3.0 Senast uppdaterad 2024-03-06
