Taltz ® (ixekizumab) injektion

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Taltz® ▼ (ixekizumab): Daktylit

Hos patienter med befintlig daktylit resulterade behandling med ixekizumab Q4W förbättring av dactylit vid vecka 24 jämfört med placebo.

Detailed Information

Compared with placebo, there were significantly more dactylitis responders (LDI-B=0) at week 24 for both ixekizumab dosing groups and for the active arm (p≤.001 for all).1

At week 24 in the SPIRIT-P2 trial, compared with placebo, more patients achieved complete resolution of dactylitis in both the ixekizumab Q4W group (p=.002) and the Q2W group.2

An integrated analysis of SPIRIT-P1 and SPIRIT-P2 demonstrated that significantly more patients treated with ixekizumab vs placebo had resolution of dactylitis at 24 weeks.3

The dosing schedule IXE Q2W mentioned in this statement is not consistent with the approved dosing schedule for psoriatic arthritis in the Taltz summary of product characteristics. Please refer to the Taltz summary of product characteristics for approved dosing.4

Description of Dactylitis Outcome Measures

Dactylitis is swelling and inflammation of the whole digit.5

The severity of dactylitis was assessed by the LDI-B. For each digit that is dactylitic, as defined by a minimum increase of 10% in circumference of the dactylitic digit (A) over the contra-lateral digit (B), the ratio (A/B) of the circumference of the affected digit to the circumference of the digit on the opposite hand or foot was measured. The calculated ratio (A/B) is then subtracted by 1, multiplied by 100 and then multiplied by a tenderness score (C) of 0 (not tender) or 1 (tender). The results of each digit are then added to produce the LDI-B total score.1,2

SPIRIT-P1 included an evaluation of the LDI-B for those patients with dactylitis at baseline as a secondary endpoint. A post hoc analysis was conducted for those patients with dactylitis and LDI-B>0 at baseline.1 SPIRIT-P2 included a pre-specified secondary endpoint of LDI-B in those patients with dactylitis and LDI-B>0 at baseline.2

Dactylitis Clinical Trial Results

Results Through Week 24

SPIRIT-P1

In SPIRIT-P1, 38% of all patients had baseline dactylitis.1

Compared with placebo, there were significantly more responders (LDI-B=0) at week 24 for both ixekizumab dosing groups and for the active arm (p≤.001 for all).1

Table 1. Improvement in Dactylitis in the SPIRIT-1 Trial at Weeks 12 and 241

 

PBO

IXE Q4W

IXE Q2W

ADA Q2W

Week 12

N=28

N=39

N=26

N=18

LDI-B=0, %

53.6

74.4

69.2

61.1

LS mean change (SE) from baseline in LDI-B

-36.3 (10.3)

-72.8 (8.8)a

-63.9 (10.6)b

-62.1 (11.9)

Week 24

N=28

N=39

N=26

N=18

LDI-B=0, %

25.0

79.5a

76.9a

77.8a

LS mean change (SE) from baseline in LDI-B

-33.7 (9.7)

-75.4 (8.1)a

-66.1 (9.8)c

-76.0 (10.9)a

Abbreviations: ADA = adalimumab; IXE = ixekizumab; LDI-B = Leeds Dactylitis Index-Basic; LS = least-squares; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks.

a p≤.001 vs PBO.

b p≤.05 vs PBO.

c p≤.01 vs PBO.

SPIRIT-P2

In SPIRIT-P2, 17% of all patients had baseline dactylitis.2

At week 24 in the SPIRIT-P2 trial, compared with placebo, more patients achieved complete resolution of dactylitis in both the ixekizumab Q4W group (p=.002) and the Q2W group.2 See Table 2 for results.

Table 2. Improvement in Dactylitis in the SPIRIT-P2 Trial at Week 242

 

PBO
(N=118)

IXE Q4W
(N=122)

IXE Q2W
(N=123)

LDI-B=0, %a

21

75b

50

LS mean change (SE) from baseline in LDI-Ba

-36.2 (8.4)

-34.7 (6.7)

-32.1 (6.7)

Abbreviations: IXE = ixekizumab; LDI-B = Leeds Dactylitis Index-Basic; LS = least-squares; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks.

a Assessed in patients with LDI>0.

b p=.002 vs PBO.

In a prespecified exploratory analysis, compared with placebo, a significantly greater proportion of patients in the ixekizumab Q4W group had resolution of dactylitis at week 16 (p<.05) as well as week 24 (p<.01) (see Figure 1).2

Figure 1. Resolution of Dactylitis in SPIRIT-P2 Through Week 242

Abbreviations: LDI-B = Leeds Dactylitis Index-Basic; Q2W = 80 mg every 2 weeks; Q4W = 80 mg every 4 weeks.
* p<.05 vs placebo.
p<.01 vs placebo.

Week 52 Results

SPIRIT-P1

Overall, in patients from the extension period population with LDI-B>0 at baseline in SPIRIT-P1, at week 52 complete resolution of dactylitis was achieved by

  • 81% of patients in the ixekizumab Q4W group, and

  • 75% of patients in the ixekizumab Q2W group.6

SPIRIT-P2

In the extension period population of SPIRIT-P2, of the patients with LDI-B>0 at baseline, at week 52 complete resolution of dactylitis was achieved by

  • 21/28 (75.0%) of patients in the ixekizumab Q4W/ixekizumab Q4W group, and

  • 11/20 (55.0%) of patients in the ixekizumab Q2W/ixekizumab Q2W group.7

Post hoc Integrated Analysis Results

The integrated analysis set of SPIRIT-P1 and SPIRIT-P2 was composed of 679 patients. Of these, 23% (n=155 of 676) had baseline dactylitis (LDI >0).5

As illustrated in Figure 2, an integrated analysis of SPIRIT-P1 and SPIRIT-P2 demonstrated that significantly more patients treated with ixekizumab vs placebo had greater mean improvements from baseline and rates of resolution of dactylitis at 24 weeks.3

Figure 2. SPIRIT-P1 and SPIRIT-P2 Integrated Clinical Trial Dataset: LDI-B Resolution (LDI-B=0) at Week 24 in Patients With Dactylitis (LDI-B >0) at Baseline, NRI3

Abbreviations: LDI-B = Leeds Dactylitis Index-Basic; IXE Q2W = ixekizumab 80 mg every 2 weeks following 160 mg starting dose; IXE Q4W = ixekizumab 80 mg every 4 weeks following 160 mg starting dose; NRI = nonresponder imputation; PBO = placebo.

** p<.001 vs PBO.

Therapeutic Indication

Ixekizumab, alone or in combination with methotrexate, is indicated for the treatment of active psoriatic arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drug (DMARD) therapies.4

References

1. 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

2. 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

3. 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.

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

5. Gladman DD, Orbai AM, Klitz U, et al. Ixekizumab and complete resolution of enthesitis and dactylitis: integrated analysis of two phase 3 randomized trials in psoriatic arthritis. Arthritis Res Ther. 2019;21(1):38. http://dx.doi.org/10.1186/s13075-019-1831-0

6. Mease PJ, Okada M, Kishimoto M, et al. Efficacy and safety of ixekizumab in patients with active psoriatic arthritis: 52-week results from a phase 3 study (SPIRIT P1). Abstract presented at: European League Against Rheumatism (EULAR) Congress; June 8-11, 2016; London, England.

7. 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

8. Genovese M, Combe B, Kremer J, et al. Efficacy and safety of ixekizumab in patients with active psoriatic arthritis and previous inadequate response to TNF inhibitors: 52-week results from a phase 3 study. Poster presented at: 2018 Annual Meeting of the European League Against Rheumatism (EULAR); June 13-16, 2018; Amsterdam, Netherlands.

Glossary

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

bDMARD = biologic disease-modifying antirheumatic drug

EQ-5D VAS = European Quality of Life - 5 Dimensions Visual Analog Scale

HAQ-DI = Health Assessment Questionnaire-Disability Index

LDI-B = Leeds Dactylitis Index-Basic

PsA = psoriatic arthritis

Q2W = every 2 weeks

Q4W = every 4 weeks

TNF = tumor necrosis factor

VAS = Visual Analog Scale

Appendix: Clinical Trial Design

The efficacy and safety of ixekizumab in patients with PsA was assessed in SPIRIT-P1 and SPIRIT-P2 clinical trials. The primary objective in both trials was the proportion of patients who achieved ACR20 in the ixekizumab group compared with the placebo group after 24 weeks.1,2

Brief clinical trial descriptions are included in Figure 3 and Figure 4.

SPIRIT-P1 (N=417) was 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 open-label extension period of up to 3 years.1

SPIRIT-P2 (N=363) was 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 open-label extension period of up to 3 years.2

Figure 3. SPIRIT-P1 Study Design Including Extension Period up to Week 526

Abbreviations: ADA = 40 mg adalimumab every 2 weeks (active reference arm); IXE Q2W = 80 mg ixekizumab every 2 weeks; IXE Q4W = 80 mg ixekizumab every 4 weeks; PBO = placebo every 2 weeks; RT = rescue therapy.

Note: All ixekizumab patients (starting ixekizumab at weeks 0, 16, or 24) received a 160-mg starting dose (as 2 injections) followed by ixekizumab 80 mg Q2W or Q4W; criteria for defining inadequate responders were blinded to investigators.

a Plus RT in inadequate responders.

Figure 4. SPIRIT-P2 Study Design Including Extension Period up to Week 1568

Abbreviations: IR = inadequate responder; IXE = ixekizumab; IXE Q2W = 80 mg ixekizumab every 2 weeks; IXE Q4W = 80 mg ixekizumab every 4 weeks; PBO = placebo; R = randomization; SJC = swollen joint count; RT = rescue therapy; TJC = tender joint count.
a
Inadequate responders in IXE arms at week 16 maintained their IXE dose, but received RT (modifications to the patient’s background therapy).
b
Inadequate responders in the PBO arm at week 16 were randomized to IXE Q2W + RT or IXE Q4W + RT after a 160-mg starting dose. Responders continued on PBO until week 24.
c
Patients receiving PBO until week 24 were randomized to IXE Q2W or IXE Q4W after a 160-mg starting dose.
d
Primary endpoint.
e
Patients failing to demonstrate at least 20% improvement from baseline in both TJC and SJC at week 32 or any subsequent visit were discontinued.

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 2019 M04 24


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