Taltz ® (ixekizumab) injektion

För fullständig produktresumé för Taltz® se FASS.

Denna information är endast avsedd för sjukvårdspersonal verksam i Sverige och som svar på din fråga. Informationen nedan är på engelska

Vilken långtidseffekt har Taltz (ixekizumab) vid behandling av psoriasisartrit?

Patienter som behandlades med ixekizumab i SPIRIT-P1 och -P2 kliniska studier, hade ihållande förbättringar i American College of Rheumatology (ACR) svarsfrekvenser under 156 veckor.

SE_cFAQ_IXE313_MAINTENANCE_LONG_TERM_EFFICACY_PsA
SE_cFAQ_IXE313_MAINTENANCE_LONG_TERM_EFFICACY_PsA
en-GB

Content overview

Additional information on the three SPIRIT studies is available in the Appendix: Clinical Trial Study Designs.

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.1

SPIRIT-P1 and SPIRIT-P2 long-term efficacy results 

SPIRIT-P1 results through 156 weeks

In the SPIRIT-P1 study through 156 weeks, patients treated with ixekizumab experienced persistent improvements in 

The ACR20 observed response was

  • 95% for the every 4 weeks (Q4W) group and
  • 88% for the every 2 weeks (Q2W) group.4  

The nonresponder imputation ACR20 response was 51% in both treatment arms.4

ACR20 Response in SPIRIT-P1 Through 156 Weeks, ITT Population, in Patients Originally Randomized to Ixekizumab2,4

Abbreviations: ACR20 = 20% improvement from baseline in American College of Rheumatology Index; ITT = intent to treat; IXE = ixekizumab 80 mg; MI = multiple imputation; mNRI = modified nonresponder imputation; NRI = nonresponder imputation; Q2W = every 2 weeks; Q4W = every 4 weeks.

ACR50 and ACR70 Responses in SPIRIT-P1 Through 156 Weeks, mNRI, ITT Population, in Patients Originally Randomized to Ixekizumab2,4

Abbreviations: ACR50 = 50% improvement in American College of Rheumatology criteria; ACR70 = 70% improvement in American College of Rheumatology criteria; ITT = intent to treat; IXE = ixekizumab 80 mg; mNRI = modified nonresponder imputation; Q2W = every 2 weeks; Q4W = every 4 weeks.

PASI Response Rates in SPIRIT-P1 Through 156 Weeks, mNRI, ITT Population With Psoriatic Lesions ≥3%BSA at Baseline, in Patients Originally Randomized to Ixekizumab4

Abbreviations: BSA = body surface area; ITT = intent to treat; IXE = ixekizumab 80 mg; mNRI = modified 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; Q2W = every 2 weeks; Q4W = every 4 weeks.

SPIRIT-P2 results through 156 weeks 

In the SPIRIT-P2 study, improvements in the signs and symptoms of psoriatic arthritis persisted up to 3 years in patients who received ixekizumab Q4W or Q2W for 156 weeks, as measured by

The findings were consistent with efficacy responses observed during earlier treatment periods of SPIRIT-P2 and were comparable with long-term responses in biologic-naïve patients in SPIRIT-P1.6

ACR Results in SPIRIT-P2 Through 156 Weeks, mNRI, ITT Population6

Abbreviations: 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; ITT = intent-to-treat; IXE = ixekizumab 80 mg; mNRI = modified nonresponder imputation; Q2W = every 2 weeks; Q4W = every 4 weeks.

A post-hoc analysis examined the observed response rates for LDA and remission composite measures through 156 weeks (3 years) for patients participating in SPIRIT-P1 and SPIRIT-P2 trials.7

PASI Results in SPIRIT-P2 Through 156 Weeks in Patients With BSA ≥3% at Baseline, mNRI, ITT Population6

Abbreviations: BSA = body surface area; ITT = intent-to-treat; IXE = ixekizumab 80 mg; mNRI = modified 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; Q2W = every 2 weeks; Q4W = every 4 weeks.

Treat-to-target outcomes in SPIRIT-P1 and SPIRIT-P2

Patients achieved LDA or remission disease activity targets by week 24. These responses were sustained through 156 weeks (3 years).7  

Similar response trajectories were observed in both patients who were bDMARD-naïve and patients with a previous inadequate response to TNF inhibitors (Observed Response Rates for Low Disease Target Measures Up to 156 Weeks in SPIRIT-P1 and SPIRIT-P2).7

Observed Response Rates for Low Disease Target Measures Up to 156 Weeks in SPIRIT-P1 and SPIRIT-P27

Low Disease Measure, n (%)

SPIRIT-P1

SPIRIT-P2

IXE Q4W
(N=107)

IXE Q2W
(N=103)


IXE Q4W
(N=122)

IXE Q2W
(N=123)

Week 24

Week 156

Week 24

Week 156

Week 24

Week 156

Week 24

Week 156

MDA

32 (37.6)

36 (59.0)

43 (50.6)

44 (71.0)

34 (35.1)

33 (47.8)

29 (31.5)

29 (53.7)

VLDA

11 (12.9)

18 (29.0)

12 (14.0)

21 (33.9)

15 (15.5)

16 (22.9)

4 (4.3)

11 (20.0)

DAPSA LDA

51 (60.0)

54 (88.5)

60 (71.4)

56 (90.3)

49 (51.0)

51 (73.9)

43 (47.8)

39 (72.2)

DAPSA remission

17 (20.0)

24 (39.3)

25 (29.8)

29 (46.8)

18 (18.8)

23 (33.3)

9 (10.0)

20 (37.0)

PASDAS LDA

45 (54.2)

39 (63.9)

52 (61.9)

51 (83.6)

45 (47.9)

43 (64.2)

42 (46.7)

33 (61.1)

PASDAS NR

12 (14.5)

20 (32.8)

21 (25.0)

26 (42.6)

15 (16.0)

19 (28.4)

8 (8.9)

20 (37.0)

 Abbreviations: DAPSA = disease activity index for psoriatic arthritis; IXE Q2W = ixekizumab 80 mg every 2 weeks following a 160-mg starting dose; IXE Q4W = ixekizumab 80 mg every 4 weeks following a 160-mg starting dose; LDA = low disease activity; MDA = minimal disease activity; NR = near remission; PASDAS = psoriatic arthritis disease activity score; VLDA = very low disease activity.

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.1

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.8
Mean Change From Baseline in Individual American College of Rheumatology Components in SPIRIT-P1 and SPIRIT-P28

SPIRIT-P1

SPIRIT-P2

Q2W

Q4W

Q2W

Q4W

TJC

Baseline mean (SD)

21.5 (14.1)

20.5 (13.7)

25.0 (17.3)

21.5 (14.1)

Week 24

-16.1

-13.1

-14.9

-12.7

Week 108

-19.2

-17.6

-18.8

-18.5

SJC

Baseline mean (SD)

12.0 (7.2)

11.4 (8.2)

13.4 (11.5)

13.0 (11.1)

Week 24

-10.5

-8.5

-9.7

-10.4

Week 108

-11.6

-9.5

-11.8

-10.5

PhyGA

Baseline mean (SD)

58.5 (19.0)

57.6 (18.7)

64.6 (16.8)

60.3 (20.9)

Week 24

-45.4

-39.6

-40.6

-40.4

Week 108

-49.0

-44.4

-50.5

-45.9

PatGA

Baseline mean (SD)

62.5 (19.9)

62.7 (19.1)

66.0 (20.5)

66.4 (20.5)

Week 24

-40.0

-39.5

-31.9

-34.1

Week 108

-47.2

-37.7

-39.1

-37.4

Pain VAS

Baseline mean (SD)

58.4 (21.7)

60.1 (19.4)

62.7 (20.9)

63.9 (21.4)

Week 24

-35.4

-33.9

-28.5

-30.4

Week 108

-41.6

-34.4

-34.3

-33.4

HAQ-DI

Baseline mean (SD)

1.2 (0.6)

1.2 (0.5)

1.2 (0.6)

1.2 (0.6)

Week 24

-0.53

-0.51

-0.36

-0.42

Week 108

-0.61

-0.56

-0.49

-0.45

CRP

Baseline mean (SD)

15.1 (25.9)

12.8 (16.4)

13.5 (26.1)

17.0 (27.5)

Week 24

-10.5

-8.6

-8.5

-12.4

Week 108

-13.0

-9.1

-5.4

-15.4

Abbreviations: CRP = C-reactive protein; HAQ-DI = Health Assessment Questionnaire-Disability Index; PatGA = Patient's Global Assessment; PhyGA = Physician's Global Assessment; Q2W = every 2 weeks; Q4W = every 4 weeks; SJC = swollen joint count; TJC = tender joint count; VAS = Visual Analog Scale.

SPIRIT-P3 results through 104 weeks  

In the SPIRIT-P3 study, MDA 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 ≤1.9

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.9

  • Of those 158 patients who met the MDA criteria, 77 achieved very low disease activity (VLDA), defined as meeting all 7 MDA components, during open-label treatment with ixekizumab Q2W.
  • 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.
  • Of the 38 patients who achieved MDA (but not VLDA) in the open-label treatment period, 19 maintained MDA.10

References

1Taltz [summary of product characteristics]. Eli Lilly and Company (Ireland) Limited, Ireland

2Chandran V, van der Heijde D, Fleischmann RM, et al. Ixekizumab treatment of biologic-naïve patients with active psoriatic arthritis: 3-year results from a phase III clinical trial (SPIRIT-P1). Rheumatology (Oxford). 2020;59(10):2774-2784. https://doi.org/10.1093/rheumatology/kez684

3Chandran 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). 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

4Chandran 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.

5Orbai AM, Gratacós J, Turkiewicz A, et al. Efficacy and safety of ixekizumab in patients with psoriatic arthritis and inadequate response to TNF inhibitors: 3-year follow-up (SPIRIT-P2). Rheumatol Ther. 2021;8(1):199-217. http://dx.doi.org/10.1007/s40744-020-00261-0

6Gratacos 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). Poster presented at: European League Against Rheumatism (Virtual); June 3-6, 2020.

7Kavanaugh A, Helliwell P, Sesin C, et al. Low disease thresholds up to three years in ixekizumab-treated patients with psoriatic arthritis in SPIRIT-P1 and SPIRIT-P2. Poster presented at: 12th Annual International Congress on Spondyloarthridities; September 9-11, 2021; Ghent, Belgium.

8Turkiewicz 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.

9Coates LC, Pillai SG, Tahir H, et al; SPIRIT-P3 Study Group. Withdrawing ixekizumab in patients with psoriatic arthritis who achieved minimal disease activity: results from a randomized, double-blind withdrawal study. Arthritis Rheumatol. 2021;73(9):1663-1672. https://doi.org/10.1002/art.41716.

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.

11Mease 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

12van 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

13Nash 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

14Genovese 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

15Coates 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.

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.1

SPIRIT-P1

SPIRIT-P1 (N=417) was a phase 3, 24-week double-blind, placebo-controlled trial with an active reference arm in patients with active psoriatic arthritis who are naïve to bDMARDs with an extension period of up to 3 years.11

The primary objective of SPIRIT-P1 was to assess whether ixekizumab was superior to placebo in the treatment of bDMARD-naïve patients with active psoriatic arthritis, as measured by the proportion of patients achieving ACR20 response at week 24.11

Adalimumab, at the approved psoriatic arthritis dosing of 40 mg subcutaneously Q2W, was selected as an active reference arm to validate study design. The study was not powered to compare adalimumab with ixekizumab.11

Other secondary measures included

  • ACR50 and ACR70
  • PASI 75, PASI 90, and PASI 100 (only assessed in patients with psoriatic lesions ≥3% of BSA at baseline)
  • change from baseline in modified total sharp score, and 
  • resolution of dactylitis and resolution of enthesitis, as assessed by achievement of LDI-B (0) or LEI (0) (only assessed in patients who had dactylitis or enthesitis, including scores of LDI-B >0 or LEI >0 at baseline).11
SPIRIT-P1 Study Design: Double-Blind Treatment and Extension Periods11,12

Abbreviations: ADA = adalimumab; IR = inadequate responder; IXE = ixekizumab; Q2W = every 2 weeks; Q4W = every 4 weeks; R = randomization; 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, whereas 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 criteria 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 initially randomized to receive IXE Q2W (N=103), 96 entered the extension period and remained on IXE Q2W. Among patients initially randomized to receive IXE Q4W (N=107), 97 entered the extension period and remained on IXE Q4W.

SPIRIT-P2

SPIRIT-P2 (N=363) was a phase 3, 24-week double-blind, placebo-controlled trial in patients with active psoriatic arthritis and an inadequate response or intolerance to TNF inhibitor, with an extension period of up to 3 years.13

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 psoriatic arthritis who had inadequate response (distinguished by being refractory to therapy or had loss of efficacy) or where intolerant to TNF inhibitors.13

Other endpoints included

  • ACR50 and ACR70 
  • PASI 75, PASI 90, and PASI 100 (only assessed in patients with psoriatic lesions ≥3% of BSA at baseline), and
  • resolution of dactylitis and resolution of enthesitis, as assessed by achievement of LDI-B (0) or LEI (0) (only assessed in patients who had dactylitis or enthesitis, including scores of LDI-B >0 or LEI >0 at baseline).13
SPIRIT-P2 Study Design: Double-Blind Treatment and Extension Periods13,14