Taltz ® (ixekizumab) injektion

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Taltz® ▼ (ixekizumab): Effekt vid psoriasisartrit

Information om effekten av ixekizumab för behandling av aktiv psoriasisartrit är inkluderad i nedan respons.

Summary

Integrated SPIRIT-P1 and SPIRIT-P2 data show that, compared with placebo, patients who received ixekizumab had statistically significant improvements at 24 weeks in ACR20 (p<.001 vs placebo for all ixekizumab treatment groups).1

  • The primary objective of SPIRIT-P1 was to assess whether ixekizumab was superior to placebo in the treatment of bDMARD-naive patients with active PsA, as measured by the proportion of patients achieving ACR20 response at week 24. By week 24, a significantly greater percentage of ixekizumab-treated patients compared to placebo achieved responses in ACR20 (p≤.001 vs placebo for all ixekizumab treatment groups). 2

  • Through 156 weeks, patients treated with ixekizumab experienced persistent improvements (missing data imputed using NRI) in ACR20. 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.3

  • The primary objective of SPIRIT-P2 was to assess superiority of ixekizumab 80 mg Q2W or 80 mg Q4W to placebo as measured by the proportion of patients achieving ACR20 at week 24 in the treatment of patients with active PsA who had inadequate response (distinguished by being refractory to therapy or had loss of efficacy) or where intolerant to TNF inhibitors. By week 24, a significantly greater percentage of ixekizumab-treated patients compared to placebo achieved responses in ACR20 (p<.0001 vs placebo for all ixekizumab treatment groups).4

  • 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. 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-P1.5

Note: The dosing schedule IXEQ2W mentioned in this response is not consistent with the approved dosing schedule for psoriasis arthritis in the Taltz summary of product characteristics. Please refer to the Taltz summary of product characteristics for approved dosing.6

SPIRIT-P1 Efficacy Evaluation

Study Design

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.2

Adalimumab, at the approved PsA dosing of 40 mg SC Q2W, was selected as an active reference arm to validate study design. The study was not powered to compare adalimumab with ixekizumab.2

The primary objective of SPIRIT-P1 was to assess whether ixekizumab was superior to placebo in the treatment of bDMARD-naive patients with active PsA, as measured by the proportion of patients achieving ACR20 response at week 24.2

Data Through 24 Weeks

A total of 417 patients entered, and 382 (91.6%) completed, the 24-week double-blind treatment period.7

By week 24, a significantly greater percentage of ixekizumab-treated patients compared to placebo achieved responses in

  • ACR20, ACR50, and ACR70 (p≤.001 vs placebo for all ixekizumab treatment groups)

  • PASI 75, PASI 90, and PASI 100 (p≤.001 vs placebo for all ixekizumab treatment groups)

  • LSM change from baseline mTSS (p≤.01 vs placebo for IXE Q4W and p≤.001 vs placebo for IXE Q2W)

  • LDI-B (0) (p≤.001 vs placebo for both ixekizumab treatment arms), and

  • LEI (0) (p≤.025 for ixekizumab Q2W and p≤.01 for ixekizumab Q4W).2

Data Through 156 Weeks

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.8 

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

  • ACR20, ACR50, and ACR 70

  • PASI 75, PASI 90, and PASI 100

  • LDI-B (0), and 

  • LEI (0).8

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.3

SPIRIT-P2 Efficacy Results

Study Design

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.4

The primary objective of SPIRIT-P2 was to assess superiority of ixekizumab 80 mg Q2W or 80 mg Q4W to placebo as measured by the proportion of patients achieving ACR20 at week 24 in the treatment of patients with active PsA who had inadequate response (distinguished by being refractory to therapy or had loss of efficacy) or where intolerant to TNF inhibitors.4

Data Through 24 Weeks

A total of 363 patients were randomized, and 314 (86.5%) completed the 24-week double-blind treatment period.4

By week 24, a significantly greater percentage of ixekizumab-treated patients compared to placebo achieved responses in

  • ACR20, ACR50, and ACR70 (p<.0001 vs placebo for all ixekizumab treatment groups)

  • PASI 75, PASI 90, and PASI 100 (p≤.001 vs placebo for all ixekizumab treatment groups), and 

  • LDI-B (0) (p=.002 for IXE Q4W).4

At week 24, compared with placebo, there were no statistically significant differences in achievement of

  • LDI-B (0) or LEI (0) in the IXE Q2W treatment arm, or

  • LEI (0) in the IXE Q4W treatment arm.4

Data Through 108 Weeks

Overall, 54.2% of randomized patients completed 108 weeks of treatment. Mandatory discontinuation criteria dictated that patients failing to demonstrate at least 20% improvement from baseline in both TJC and SJC at week 32 or any subsequent visit were discontinued.9,10

Responses at in ACR20, ACR50, and ACR70 at 108 weeks in the ITT population are shown in Table 1.

Patients on ixekizumab Q2W and ixekizumab Q4W continued to show achievement of LEI (0) and LDI-B (0), and improvements from baseline PASI. 

Table 1. SPIRIT-P2 Efficacy Results: Percent Response at 108 Weeks (ITT Population; mNRI)10

Efficacy Measure

IXE Q4W (n=122)

IXE Q2W  (n=123)

ACR20, n (%) 

73 (59.6) 

59 (47.9) 

ACR50, n (%) 

56 (46.2) 

40 (32.5)

ACR70, n (%) 

28 (23.2) 

27 (22.6) 

Abbreviations: ACR20/50/70 = American College of Rheumatology 20/50/70 index; ITT = intent-to-treat; IXE = ixekizumab; mNRI = modified NRI; n = number of patients in the specified analysis population; Q2W = every 2 weeks; Q4W = every 4 weeks.

Data Through 156 Weeks

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).5

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-P1.5

SPIRIT-P1 and SPIRIT-P2 24-Week Integrated Efficacy Analysis

Integrated SPIRIT-P1 and SPIRIT-P2 data show that, compared with placebo, patients who received ixekizumab had statistically significant improvements at 24 weeks in

  • ACR20, ACR50, and ACR70 (p<.001 vs placebo for all ixekizumab treatment groups)

  • PASI 75, PASI 90, and PASI 100 (p<.001 vs placebo for all ixekizumab treatment groups)

  • LEI (p<.05 vs placebo for all ixekizumab treatment groups), and

  • LDI-B responses (p<.001 vs placebo for all ixekizumab treatment groups).1,11

Improvement in Individual American College of Rheumatology Components Up To Week 108

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.12

References

1. Combe B, Nash P, Adams D, et al. Integrated efficacy and safety results from SPIRIT-P1 and SPIRIT-P2, two phase 3 trials of ixekizumab for the treatment of psoriatic arthritis. Poster presented at: 26th Congress of the European Academy of Dermatology and Venereology (EADV); September 13-17, 2017; Geneva, Switzerland.

2. Mease PJ, van der Heijde D, Ritchlin CT, et al. 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

3. Chandran 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.

4. Nash P, Kirkham B, Okada M, et al. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomized, 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

5. Gratacos 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.

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

7. van 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

8. Chandran V, Fleischmann R, Lespessailles E, et al. THU0333 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. http://dx.doi.org/10.1136/annrheumdis-2018-eular.2137

9. Genovese 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

10. Orbai AM, Gellett AM, Kerr L, Constantin A. Efficacy and safety of ixekizumab in patients with active psoriatic arthritis and previous inadequate response to TNF inhibitors: two-year follow-up from a phase 3 study [abstract]. Arthritis Rheumatol. 2018;70(suppl 10). https://acrabstracts.org/abstract/efficacy-and-safety-of-ixekizumab-in-patients-with-active-psoriatic-arthritis-and-previous-inadequate-response-to-tnf-inhibitors-two-year-follow-up-from-a-phase-3-study/

11. Gladman DD, Orbai AM, Gallo G, Birt J, et al. SAT0321 Ixekizumab treatment significantly improves enthesitis and dactylitis in patients with active psoriatic arthritis: results from the spirit trials [abstract]. Ann Rheum Dis. 2018;77(suppl 2):1025. http://dx.doi.org/10.1136/annrheumdis-2018-eular.2325

12. Turkiewicz 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.

Glossary

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

CRP = C-reactive protein

DAPSA = Disease Activity in Psoriatic Arthritis

HAQ-DI = Health Assessment Questionnaire-Disability Index

ITT = intent-to-treat

IXE = ixekizumab

LDA = low disease activity

LDI-B = Leeds Dactylitis Index-Basic

LEI = Leeds Enthesitis Index

LSM = least squares mean

MDA = minimal disease activity

mTSS = modified Total Sharp Score

NRI = nonresponder imputation

PASI 100 = 100% improvement from baseline in 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

PatGA = Patient's Global Assessment

PhyGA = Physician's Global Assessment

PsA = psoriatic arthritis

Q2W = every 2 weeks

Q4W = every 4 weeks

SC = subcutaneous

SJC = swollen joint count

TJC = tender joint count

TNF = tumor necrosis factor

VAS = Visual Analog Scale

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Datum fӧr senaste ӧversyn 2020 M06 03


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