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    • SELECT-PsA 1: Study design

      A Phase 3 study investigating the efficacy and safety of RINVOQ compared with placebo and adalimumab for the treatment of active PsA in patients with an inadequate response to nonbiological DMARDs1,2


      The approved dose of RINVOQ is 15 mg once daily. Upadacitinib 30 mg QD is not an approved dose.

      All subjects received x-rays of hands and feet at screening, Week 24, Week 56, Week 104, and Week 152. At Week 16, rescue therapy was offered to subjects classified as nonresponders (defined as not achieving at least 20% improvement in tender joint count and swollen joint count at both Week 12 and Week 16). At Week 24, all placebo subjects were switched to RINVOQ 15 mg QD or upadacitinib 30 mg QD (1:1 ratio) regardless of response.    

       

      Primary 
      ACR20 response for RINVOQ vs placebo at Week 12

      Key ranked secondary endpoints
      (RINVOQ vs placebo unless noted)

      • Change from baseline in HAQ-DI 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 mTSS at Week 24
      • Proportion of subjects achieving MDA at Week 24
      • Proportion of subjects with resolution of enthesitis (LEl=0) at Week 24
      • ACR20 response rate at Week 12 (noninferiority vs adalimumab)
      • Change from baseline in SF-36 PCS 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 (LDl=0) at Week 24
      • Change from baseline in patient’s assessment of pain NRS at Week 12 (superiority vs adalimumab)
      • Change from baseline in HAQ-DI at Week 12 (superiority vs adalimumab); and
      • Change from baseline in SAPS at Week 16  

      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.    

      *Superiority of RINVOQ 15 mg vs adalimumab could not be demonstrated, which prevented the testing of significance for secondary endpoints lower in the testing hierarchy.
      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
      • Presence at screening of either ≥1 erosion on x-ray as determined by central imaging review or hs-CRP >ULN
      • Diagnosis of active plaque psoriasis or documented history of plaque psoriasis
      • Inadequate response or intolerance to treatment with at least one nonbiologic DMARD*
      • On ≤2 nonbiologic DMARDs
      • Prior exposure to any JAK inhibitor
      • Prior exposure to any bDMARD

      At baseline, 1,393 (82%) of patients were on at least 1 concomitant non-bDMARD; 1,084 (64%) of patients received concomitant MTX, only; and 311 (18%) of patients were on monotherapy.    

      *Lack of efficacy after ≥12 weeks of therapy; intolerance or contraindication as defined by investigator

      ACR20: improvement of at least 20% in the American College of Rheumatology core criteria; bDMARD: biological disease-modifying antirheumatic drug; CASPAR: Classification Criteria for Psoriatic Arthritis; DMARD: disease-modifying antirheumatic drug; EOW: every other week; hs-CRP: high-sensitivity C-reactive protein; JAK: Janus kinase;  MTX: methotrexate; OLE: open-label extension; QD: once daily; SJC: swollen joint count; TJC: tender joint count; ULN: upper limit of normal.    

        

      In patients with active PsA and an inadequate response to nonbiologic DMARDs 

      RINVOQ joint symptom improvement was superior to placebo for ACR20 at Week 12

      SELECT-PsA 1: ACR20/50/70 response rates at Week 12 (NRI)1,2 

      *P≤0.001 vs placebo, statistically significant in the multiplicity-controlled analysis.
      P≤0.001 vs adalimumab for noninferiority, statistically significant in the multiplicity-controlled analysis.

      ACR20 for RINVOQ vs placebo at Week 12 was a primary multiplicity-controlled endpoint.
      ACR20 noninferiority vs adalimumab at Week 12 was a key ranked secondary, multiplicity-controlled endpoint.

      In patients with active PsA and an inadequate response to nonbiologic DMARDs

      ACR20 response rates over time

      SELECT-PsA 1: ACR20 response rates (NRI)1-4

      *P≤0.001 vs placebo, statistically significant in the multiplicity-controlled analysis.
      P≤0.001 vs adalimumab for noninferiority, statistically significant in the multiplicity-controlled analysis.
      Nominal P≤0.001 vs placebo3#Nominal P≤0.05 vs adalimumab3§Not significant (nominal P=0.06) vs adalimumab4
      Nominal P-values denote data not controlled for multiplicity. No clinical inferences can be drawn.

      Superiority vs adalimumab in ACR20 at Week 12 could not be demonstrated.2

      At Week 24, all patients randomized to placebo were switched to RINVOQ 15 mg or upadacitinib 30 mg QD in a blinded manner.

      In patients with active PsA and an inadequate response to nonbiologic DMARDs

      ACR50 response rates over time

      SELECT-PsA 1: ACR50 response rates (NRI)1-4

      Nominal P≤0.001 vs placebo.3  #Nominal P≤0.05 vs adalimumab.3,4
      Nominal P-values denote data not controlled for multiplicity. No clinical inferences can be drawn.

      At Week 24, all patients randomized to placebo were switched to RINVOQ 15 mg or upadacitinib 30 mg QD in a blinded manner.

      Primary endpoint was the proportion of patients achieving ACR20 response with RINVOQ vs placebo at Week 12. ACR50 for RINVOQ vs placebo at Week 12 was an additional key secondary endpoint, not multiplicity-controlled. Comparison vs adalimumab was not prespecified.

      In patients with active PsA and an inadequate response to nonbiologic DMARDs

      ACR70 response rates over time

      SELECT-PsA 1: ACR70 response rates (NRI)1-4

      Nominal P≤0.001 vs placebo3, #Nominal P≤0.05 vs adalimumab3¥Nominal P≤0.01 vs adalimumab4
      Nominal P-values denote data not controlled for multiplicity. No clinical inferences can be drawn.

      At Week 24, all patients randomized to placebo were switched to RINVOQ 15 mg or upadacitinib 30 mg QD in a blinded manner.

      Primary endpoint was the proportion of patients achieving ACR20 response with RINVOQ vs placebo at Week 12. ACR70 for RINVOQ vs placebo at Week 12 was an additional key secondary endpoint, not multiplicity-controlled. Comparison vs adalimumab was not prespecified.

      DATA LIMITATIONS: Data not labeled as a ranked primary or secondary endpoint were prespecified nonranked endpoints not controlled for multiplicity with nominal P-values; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made. Missing data were handled using NRI. 

      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; EOW: every other week; NRI: nonresponder imputation; QD: once daily.

       

      In patients with active PsA and an inadequate response to nonbiologic DMARDs

      Joint protection vs placebo across radiographic endpoints

      SELECT-PsA 1: Inhibition of structural joint damage progression at Week 24 (linear extrapolation)1,2

      *P≤0.001 vs placebo, statistically significant in multiplicity-controlled analysis.

      DATA LIMITATIONS: Data not labeled as a primary or ranked secondary endpoint were prespecified but not controlled for multiplicity. Nominal P-values are provided where available. Treatment differences could represent chance findings. No clinical conclusions can be made from these comparisons. No statistical comparisons were made between RINVOQ and adalimumab groups for radiographic endpoints.

      AII patients on placebo switched to RINVOQ at Week 24; all placebo data at Week 56 were derived using linear extrapolation.

      csDMARD: conventional synthetic disease-modifying antirheumatic drug; EOW: every other week; mTSS: modified total Sharp score; QD: once daily.

       

      Efficacy across key PsA manifestations

      In patients with active PsA and an inadequate response to nonbiologic DMARDs

      PASI 75 response at Week 16 (NRI)1,2

      *P≤0.001 vs placebo, statistically significant in the multiplicity-controlled analysis.
      For subjects with ≥3% BSA psoriasis at baseline (n=211, 211, and 214, repectively, for placebo, adalimumab, and RINVOQ).

      The percentages in brackets show 95% confidence interval.

       

      Resolution of enthesitis (LEI=0) at Week 24 (NRI)1,2

      *P≤0.001 vs placebo, statistically significant in the multiplicity-controlled analysis.
      For subjects with baseline presence of enthesitis (LEl>0, n=241, 265, and 270, respectively, for placebo, adalimumab, and RINVOQ). 

      The percentages in brackets show 95% confidence interval.

      Resolution of dactylitis (LDI=0) at Week 24 (NRI)1,2

      For subjects with baseline presence of dactylitis (LDI>0, n=126, 127, and 136, respectively, for placebo, adalimumab, and RINVOQ).
      #RINVOQ 15 mg did not meet superiority vs adalimumab for ACR20 response, thus statistical vs placebo regarding proportion of patients achieving resolution of dactylitis could not be tested under the hierarchical analysis plan.

      The percentage in brackets show 95% confidence interval.

      Subjects rescued at Week 16 were imputed as nonresponders in the resolution of enthesitis and dactylitis at Week 24. 

      DATA LIMITATIONS: Data not labeled as a ranked primary or secondary endpoint were prespecified nonranked endpoints not controlled for multiplicity with nominal P-values; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made. Missing data were handled using NRI.

      BSA: body surface area; csDMARD: conventional synthetic disease-modifying antirheumatic drug; EOW: every other week; LDI: Leeds Dactylitis Index; LEI: Leeds Enthesitis Index; NRI: nonresponder imputation; PASI 75: Psoriasis Area and Severity Index 75% improvement; QD: once daily.

       

      In patients with active PsA and an inadequate response to nonbiologic DMARDs

      Significantly more patients treated with RINVOQ achieved MINIMAL DISEASE ACTIVITY vs placebo at Week 24

      SELECT-PsA 1: Minimal disease activity at Week 24 (NRI)1,2

      *P≤0.001 vs placebo, statistically significant in the multiplicity-controlled analysis.

      Minimal disease activity (MDA) is achieved when meeting 5 of 7 criteria:3

      • 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
         

      Subjects rescued at Week 16 were imputed as nonresponders in the MDA analysis. Missing data were handled using NRI.

      BSA-Ps: body surface area with psoriasis; csDMARD: conventional synthetic disease-modifying antirheumatic drug; EOW: every other week; 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 RA1,2*

      SELECT-PsA 1: Adverse events through Week 242

      Most common adverse events: In SELECT-PsA 1, the most common AEs were upper respiratory tract infection, nasopharyngitis, blood CPK increase, ALT increase, and AST increase.2***

      *A higher incidence of acne and bronchitis was observed in patients treated with upadacitinib 15 mg (1.3% and 3.9%, respectively) compared to placebo (0.3% and 2.7%, respectively). In patients treated with RINVOQ in combination with methotrexate therapy compared to patients treated with monotherapy, 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.  There was a higher rate of serious infections in patients ≥65 years of age, although data are limited.1
      **Lung cancer metastasis.
      ***Treatment-emergent adverse events reported in ≥5% of patients in any treatment arm through Week 24.

      AE: adverse event; ALT: alanine aminotransferase; EOW: every other week; QD: once daily.
       

      Minimiinformation

      RINVOQ® (upadacitinib), depottablett 15 mg (F), depottablett 30 mg (F), Rx, ATC-kod L04AA44 selektivt immunsuppressivt medel, JAK-hämmare. Indikationer: 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. Aktiv ankyloserande spondylit hos vuxna patienter 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. Kontraindikationer: Överkänslighet mot den aktiva substansen eller mot något hjälpämne. Aktiv tuberkulos (TB) eller aktiv allvarlig infektion. Gravt nedsatt leverfunktion. Graviditet. Varningar och försiktighet: RINVOQ ska inte påbörjas hos patienter med aktiva, allvarliga infektioner, inkl. lokala infektioner och TB. Avbryt behandling om en patient utvecklar en allvarlig infektion eller en opportunistisk infektion. Virusreaktivering, inkl. fall av reaktivering av herpesvirus (t.ex. herpes zoster), har rapporterats i kliniska studier. Vid herpes zoster ska behandlingsavbrott övervägas tills episoden upphört. Påbörja inte eller avbryt tillfälligt behandling om onormala lab-värden som anemi, neutropeni, lymfopeni och levertransaminaser påträffas. Upadacitinib associerades med ökade lipidparametrar i kliniska studier. Behandla patienter enl. kliniska riktlinjer för hyperlipidemi. Divertikulit har rapporteras i kliniska prövningar och från klinisk erfarenhet efter godkännandet för försäljning. Upadacitinib ska användas med försiktighet till patienter med divertikelsjukdom och särskilt till patienter som samtidigt långtidsbehandlas med läkemedel som medför ökad risk för divertikulit såsom NSAID, kortikosteroider och opioider. VTE har rapporterats hos patienter på upadacitinib. Avsluta behandling om symptom på DVT/LE uppstår. För fullständig information om indikation, kontraindikationer, varningar och försiktighet, biverkningar, pris och dosering, se Fass.se. För information: kontakta AbbVie AB, 08 684 44 600. Datum för översyn av produktresumén: 30 maj 2022. Begränsning av läkemedelsförmån reumatologi: RINVOQ 15 mg ingår i läkemedelsförmånerna med begränsad subvention när behandling med TNF-hämmare gett otillräcklig effekt eller inte är lämplig. Begränsning av läkemedelsförmån dermatologi: RINVOQ subventioneras för patienter >12 år med måttlig till svår atopisk dermatit, när konventionell topikal eller systemisk behandling gett otillräcklig effekt eller inte är lämplig. 

      ▼ Detta läkemedel är föremål för utökad övervakning.

      SE-RNQ-220026 v 1. Senast uppdaterad 2022-07-01

      Jag vill gärna ha mer information från en produktspecialist.

      Jag har frågor till en medicinsk expert.

      References

      1. RINVOQ produktresumé 16 december 2021
      2. McInnes IB, Anderson JK, Magrey M, et al.Trial of upadacitinib and adalimumab for psoriatic arthritis. N Engl J Med. 2021;384:1227-39.
      3. 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

       

      SE-RNQ-220011 v.1.0  Senast uppdaterad 2022-03-10