Taltz ® (ixekizumab) injektion

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Taltz (ixekizumab): Effekt vid underhållsbehandling av psoriasisartrit

I SPIRIT-P1 och -P2, bibehölls patienternas svar på ixekizumab under 156 veckor. Data från SPIRIT-P3 till 104 veckor tillhandahålls också.

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General Information

  • Two multicenter, randomized, double-blind, placebo-controlled studies (SPIRIT-P1 and SPIRIT-P2) and one trial with a 36-week open-label period followed by a randomized, double-blind withdrawal period (SPIRIT-P3) enrolled a total of 1350 patients 18 years of age and older with active PsA.
    • SPIRIT-P1 (N=417) is a phase 3, 24-week double-blind, placebo-controlled trial with an active reference arm in patients with active PsA who are naïve to bDMARDs with an extension period of up to 3 years.1
    • SPIRIT-P2 (N=363) is a phase 3, 24-week double-blind, placebo-controlled trial in patients with active PsA and an inadequate response or intolerance to TNF inhibitor, with an extension period of up to 3 years.2
    • SPIRIT-P3 (N=570) consists of a 36-week open-label period followed by a randomized double-blind withdrawal period from week 36 to week 104 in patients naïve to bDMARDs.3,4

Please note that the dosing schedule IXE Q2W mentioned in this statement is not consistent with the approved dosing schedule for psoriatic arthritis. Please refer to the Taltz Summary of Product Characteristics for approved dosing.5

SPIRIT-P1: Results Through 156 Weeks

In SPIRIT‑P1, 63 patients completed 3 years of Q4W ixekizumab treatment.5

Among the 107 patients who were randomized to ixekizumab Q4W (NRI analysis in ITT population),

  • 54 patients (50%),
  • 41 patients (38%),
  • 29 patients (27%), and
  • 36 patients (34%)

were observed to have ACR20, ACR50, ACR70, and MDA response, respectively, at Week 156.5

Of the 210 patients initially randomized to ixekizumab at week 0 (ITT)

  • 125 (60%) completed 156 weeks of treatment
  • 27 patients discontinued due to AEs, and
  • 26 patients met mandatory discontinuation criteria, defined as failing to demonstrate ≥20% improvement in both TJC and SJC at week 32 or any subsequent visit.6 

Through 156 weeks, patients treated with ixekizumab experienced persistent improvements (missing data imputed using NRI) in 

  • ACR20, ACR50, and ACR70
  • PASI 75, PASI 90, and PASI 100
  • LDI-B (0)
  • LEI (0), and
  • HAQ-DI.6,7

The ACR20 observed response was 95% for the Q4W group and 88% for the Q2W group. The NRI ACR20 response was 51% in both treatment arms.7

SPIRIT-P2: Results Through 156 Weeks

In SPIRIT‑P2, 70 patients completed 3 years of Q4W ixekizumab treatment.5

Among the 122 patients who were randomized to ixekizumab Q4W (NRI analysis in ITT population),

  • 56 patients (46%),
  • 39 patients (32%),
  • 24 patients (20%) and
  • 33 (27%)

were observed to have ACR20, ACR50, ACR70, and MDA response, respectively, at Week 156.5

Improvements in the signs and symptoms of PsA persisted up to 3 years in patients who received ixekizumab Q4W or Q2W for 156 weeks, as measured by

  • ACR20/50/70
  • PASI 75/90/100 (in those patients with BSA ≥3% at baseline)
  • DAPSA LDA or remission
  • modified MDA (6 entheseal points)
  • LDI-B=0 (in those patients with LDI-B score >0 at baseline), and
  • LEI=0 (in those patients with LEI score >0 at baseline).8

The findings were consistent with efficacy responses observed during earlier treatment periods of SPIRIT-P2 and were comparable with long-term responses in biologic-naive patients in SPIRIT-P1.8

SPIRIT-P1 and SPIRIT-P2 Integrated Data: Improvement in ACR Components to Week 108

In SPIRIT-P1 and SPIRIT-P2, similar responses for ACR 20/50/70 were seen in patients with psoriatic arthritis regardless of whether they were on concomitant cDMARDs, including MTX treatment, or not.5

Up to week 108, patients who received ixekizumab in the SPIRIT-P1 study (bDMARD-naive) and the SPIRIT-P2 study (prior inadequate response to TNF inhibitors) had similar mean changes from baseline in

  • TJC
  • SJC
  • PhyGA
  • PatGA
  • pain VAS
  • HAQ-DI, and
  • CRP.9

SPIRIT-P3

SPIRIT-P3 is a phase 3b study in which patients with active PsA who were naïve to bDMARDs and had previously had an inadequate response to at least one cDMARD received open-label treatment with ixekizumab 80 mg Q2W following a 160 mg starting dose. Patients who achieved MDA for 3 months between weeks 36 to 64 were randomized to either continue receiving ixekizumab Q2W or switch to placebo through week 104 or until relapse. During this double-blind withdrawal period, patients who relapsed by no longer meeting MDA criteria were switched back to ixekizumab Q2W through week 104.4,10

Minimal disease activity was defined as meeting at least 5 of the following 7 criteria:

  • TJC ≤1
  • SJC ≤1
  • PASI total score ≤1 or BSA ≤3%
  • Patient pain VAS score ≤15
  • Patient global disease activity VAS score ≤20
  • HAQ-DI ≤0.5, or
  • Tender entheseal points ≤1.4,10

Of the 394 patients who participated in the open-label treatment period of SPIRIT-P3, 158 (40%) met the MDA criteria for 3 consecutive months between weeks 36 to 64 and were randomized to double-blind treatment with ixekizumab Q2W or placebo.10

  • Of those 158 patients who met the MDA criteria, 77 achieved VLDA, defined as meeting all 7 MDA components, during open-label treatment with ixekizumab Q2W.10
  • Of the 40 patients who achieved VLDA in the open-label treatment period and continued ixekizumab Q2W during the randomized withdrawal phase, 30 maintained MDA.10
  • Of the 38 patients who achieved MDA (but not VLDA) in the open-label treatment period, 19 maintained MDA.10

References

1Mease PJ, van der Heijde D, Ritchlin CT, et al; SPIRIT-P1 Study Group. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2017;76(1):79-87. http://dx.doi.org/10.1136/annrheumdis-2016-209709

2Nash P, Kirkham B, Okada M, et al; SPIRIT-P2 Study Group. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet. 2017;389(10086):2317-2327. http://dx.doi.org/10.1016/S0140-6736(17)31429-0

3A long-term efficacy and safety study of ixekizumab (LY2439821) in participants with active psoriatic arthritis (SPIRIT P3). ClinicalTrials.gov identifier: NCT02584855. Updated November 15, 2019. Accessed June 18, 2020. https://www.clinicaltrials.gov/ct2/show/NCT02584855?term=SPIRIT-P3&rank=1

4Coates LC, Pillai SG, Zhang L, et al. Continuing versus withdrawing ixekizumab in patients with psoriatic arthritis who achieved sustained minimal disease activity: results from the SPIRIT-P3 study. Poster presented at: Annual Meeting of the American College of Rheumatology; November 8-13, 2019; Atlanta, Georgia.

5Taltz [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands

6Chandran V, Fleischmann R, Lespessailles E, et al. Efficacy and safety of ixekizumab in patients with active psoriatic arthritis: three year results from a phase 3 study (SPIRIT-P1) [abstract]. Ann Rheum Dis. 2018;77(suppl 2):385. Annual European Congress of Rheumatology (EULAR 2018) abstract THU0333. http://dx.doi.org/10.1136/annrheumdis-2018-eular.2137

7Chandran V, Fleischmann R, Lespessailles E, et al. Efficacy and safety of ixekizumab in patients with active psoriatic arthritis: three year results from a phase 3 study (SPIRIT-P1). Poster presented at: 2018 Meeting of the European League Against Rheumatism (EULAR); June 13-16, 2018; Amsterdam, Netherlands.

8Gratacos J, Turkiewicz A, Dokoupilova E, et al. Efficacy and safety of ixekizumab in patients with psoriatic arthritis and inadequate response to TNF inhibitors: three year results from a phase 3 study (SPIRIT-P2). Paper presented at: European League Against Rheumatism (Virtual); June 3-6, 2020.

9Turkiewicz A, Sprabery AT, Gellett AM, et al. Ixekizumab demonstrates consistent improvement to week 108 in psoriatic arthritis across individual ACR components for patients naive to biologic DMARDs or with previous inadequate response to TNF inhibitors. Poster presented at: American College of Rheumatology/ARP; November 8-13, 2019; Atlanta, GA.

10Coates L, Pillai S, Hufford M, et al. Withdrawal of ixekizumab results in loss of efficacy in multiple clinical domains in patients with psoriatic arthritis who had achieved minimal disease activity: results from the SPIRIT-P3 study. Poster presented at: Annual Meeting of the American College of Rheumatology; November 8-13, 2019; Atlanta, Georgia.

11van der Heijde D, Gladman DD, Kishimoto M, et al. Efficacy and safety of ixekizumab in patients with active psoriatic arthritis: 52-week results from a phase III study (SPIRIT-P1). J Rheumatol. 2018;45(3):367-377. http://dx.doi.org/10.3899/jrheum.170429

12Genovese MC, Combe B, Kremer JM, et al. Safety and efficacy of ixekizumab in patients with PsA and previous inadequate response to TNF inhibitors: week 52 results from SPIRIT-P2. Rheumatology. 2018;57(11):2001-2011. http://dx.doi.org/10.1093/rheumatology/key182

Glossary

ACR = American College of Rheumatology

ACR20 = 20% improvement from baseline in American College of Rheumatology Index

ACR50 = 50% improvement from baseline in American College of Rheumatology Index

ACR70 = 70% improvement from baseline in American College of Rheumatology Index

AE = adverse event

bDMARD = biologic disease-modifying antirheumatic drug

BSA = body surface area

cDMARD = conventional disease-modifying antirheumatic drug

CRP = C-reactive protein

DAPSA = Disease Activity in Psoriatic Arthritis

HAQ-DI = Health Assessment Questionnaire-Disability Index

ITT = intent-to-treat

LDA = low disease activity

LDI-B = Leeds Dactylitis Index-Basic

LEI = Leeds Enthesitis Index

MDA = minimal disease activity

NRI = nonresponder imputation

PASI = Psoriasis Area and Severity Index

PASI 75 = 75% improvement from baseline in Psoriasis Area and Severity Index

PASI 90 = 90% improvement from baseline in Psoriasis Area and Severity Index

PASI 100 = 100% improvement from baseline in Psoriasis Area and Severity Index

PatGA = Patient's Global Assessment

PhyGA = Physician's Global Assessment

PsA = psoriatic arthritis

Q2W = every 2 weeks

Q4W = every 4 weeks

SJC = swollen joint count

TJC = tender joint count

TNF = tumor necrosis factor

VAS = Visual Analog Scale

VLDA = Very Low Disease Activity 

Appendix: Clinical Trial Study Designs

Note: The dosing schedule IXE Q2W is not consistent with the approved dosing schedule for psoriatic arthritis. Please refer to the Taltz Summary of Product Characteristics for approved dosing.5

SPIRIT-P1 Study Design: Double-Blind Treatment and Extension Periods1,11

Abbreviations: ADA = adalimumab; IR = inadequate responder; IXE = ixekizumab; Q2W = every 2 weeks; Q4W = every 4 weeks; SJC = swollen joint count; TJC = tender joint count.

a All IRs (as determined by prespecified, blinded TJC and SJC criteria) at week 16 received rescue therapy and were analyzed as nonresponders at week 24. Placebo-IRs received their first dose of IXE at week 16 while ADA-IRs had an 8-week placebo washout period before beginning their first dose of IXE at week 24.
b Patients were discontinued from the study if they did not demonstrate a ≥20% improvement from baseline in both TJC and SJC at week 32 or at any subsequent visit during the study.

Notes:
Adalimumab represents an active reference arm. The study was not powered to test equivalence or noninferiority of active treatment groups to each other, including IXE vs ADA.
Among patients on IXE Q2W (N=103), 96 entered the extension period on IXE Q2W. Among patients on IXE Q4W (N=107), 97 entered the extension period on IXE Q4W.

SPIRIT-P2 Study Design: Double-Blind Treatment and Extension Periods2,12

Abbreviations: IR = inadequate responder; IXE = ixekizumab; Q2W = every 2 weeks; Q4W = every 4 weeks; SJC = swollen joint count; TJC = tender joint count.

a All IRs (as determined by prespecified, blinded TJC and SJC criteria) at week 16 received rescue therapy and were analyzed as nonresponders at week 24. Placebo-IRs received their first dose of IXE at week 16.
b Patients were discontinued from the study if they did not demonstrate a ≥20% improvement from baseline in both TJC and SJC at week 32 or at any subsequent visit during the study.

Notes: Among patients initially randomized to IXE Q2W (N=123), 107 entered the extension period on IXE Q2W. Among patients initially randomized to IXE Q4W (N=122), 111 entered the extension period on IXE Q4W.

SPIRIT-P3 Clinical Study Design4

Abbreviations: IXE = ixekizumab; MDA = minimal disease activity; PBO = placebo; Q2W = every 2 weeks; SJC = swollen joint count; TJC = tender joint count.

Patients were discontinued if they failed to demonstrate ≥20% improvement in TJC and SJC at week 24 or at any subsequent visit through week 104, except from the point of randomization until the visit after relapse for patients randomized in the double-blind withdrawal period.
b Between weeks 36 and 64, patients who achieved MDA criteria for ≥4 visits over 3 consecutive months were randomized 1:1:1 to IXE Q2W or IXE Q2W withdrawal. Patients randomized to IXE Q2W withdrawal received PBO.
Patients not meeting randomization criteria by week 64 continued on IXE Q2W until week 104.
d Patients who relapsed by no longer meeting MDA criteria received IXE Q2W until week 104.

Datum fӧr senaste ӧversyn 2020 M07 28


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