Taltz® ▼ (ixekizumab)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information. Please refer to the link for full prescribing information: Taltz Summary of Product Characteristics (SmPC)

Taltz®▼ (ixekizumab): Dosing in Heavier Patients for Plaque Psoriasis

The recommended dose of ixekizumab for moderate-to-severe psoriasis is the same for all adult patients regardless of weight.

Detailed Information

The recommended dose of ixekizumab for moderate-to-severe psoriasis is the same for all adult patients regardless of weight. Examination of body weight did not identify differences in response to ixekizumab among these subgroups at week 12 in the pivotal UNCOVER-1, -2, and -3 clinical trials in adults with moderate-to-severe plaque psoriasis.1

The recommended dose is 160 mg by subcutaneous injection (two 80 mg injections) at Week 0, followed by 80 mg (one injection) at Weeks 2, 4, 6, 8, 10, and 12, then maintenance dosing of 80 mg (one injection) every 4 weeks.2

The efficacy and safety of ixekizumab in plaque psoriasis was demonstrated regardless of the body weight.2

The below mentioned dosing schedule IXEQ4W during the first 12 weeks of treatment (induction phase) is not consistent with the approved dosing schedule for plaque psoriasis in the Taltz summary of product characteristics. Please refer to the Taltz summary of product characteristics for approved dosing. 2

The information provided herein, including that contained within the published literature, is for informational purposes only and does not constitute any treatment recommendations.

Efficacy Analyses by Weight Subgroup at Week 12

Subgroup analyses from integrated UNCOVER-1, -2, and -3 data were conducted for the primary endpoints of sPGA (0,1) and PASI 75, as well as secondary endpoints of PASI 90, PASI 100, and sPGA (0) for baseline body weight subgroups of <80 kg, ≥80 kg to <100 kg, and ≥100 kg.3

As shown in Table 1, PASI 75 and sPGA (0,1) response rates at week 12 were significantly greater in both the ixekizumab Q2W and Q4W treatment arms compared with etanercept (p≤.001; UNCOVER-2 and -3) and placebo (p≤.05) across all baseline weight subgroups (<80 kg, ≥80 to <100 kg, and ≥100 kg) despite numerically lower response rates for patients with increasing body weight.3

Optimal responses are typically less frequent with fixed dose biological agents in patients with increasing weight, especially patients weighing >100 kg.4 Ixekizumab clearance and volume of distribution increase as body weight increases. Therefore, weight may be one contributing factor to numerically lower efficacy values in heavier patients.1

Table 1. UNCOVER-1, -2, and -3: PASI and sPGA Response Rates by Weight Subgroups at Week 12, NRI1,3


<80 kg

80 to <100 kg

100 kg

<80 kg

80 to <100 kg

100 kg

<80 kg

80 to <100 kg

100 kg

<80 kg

80 to <100 kg

100 kg


PBO

ETNa

IXE Q4W

IXE Q2W

N

258

280

251

234

254

251

354

437

368

394

425

349

PASI 75, n (%)

11 (4.3)

16 (5.7)

8 (3.2)

137 (58.5)b

123 (48.4)b

93 (37.1)b

303 (85.6)bc

374 (85.6)bc

273 (74.2)bc

358 (90.9)bcd

380 (89.4)bc

299 (85.7)bcd

PASI 90, n (%)

4 (1.6)

5 (1.8)

0

72 (30.8)b

64 (25.2)b

29 (11.6)b

257 (72.6)bc

286 (65.4)bc

194 (52.7)bc

307 (77.9)bc

300 (70.6)bc

210 (60.2)bc

PASI 100, n (%)

0

1 (0.4)

0

23 (9.8)b

15 (5.9)b

9 (3.6)b

155 (43.8)bc

150 (34.3)bc

81 (22.0)bc

184 (46.7)bc

166 (39.1)bc

90 (25.8)bc

sPGA (0,1), n (%)

14 (5.4)

12 (4.3)

5 (2.0)

111 (47.4)e

107 (42.1)e

70 (27.9)e

281 (79.4)ec

344 (78.7)ec

248 (67.4)ec

338 (85.8)ecf

354 (83.3)ec

264 (75.6)ecf

sPGA (0), n (%)

0

1 (0.4)

0

26 (11.1)e

18 (7.1)b

10 (4.0)b

158 (44.6) ec

156 (35.7)ec

85 (23.1)ec

188 (47.7)ec

180 (42.4)ecf

94 (26.9)ec

Abbreviations: CMH = Cochran–Mantel–Haenszel; ETN = etanercept 50 mg twice weekly; 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; NRI = nonresponder imputation; PASI = Psoriasis Area and Severity Index; PBO = placebo; sPGA = static Physician Global Assessment.

a Included in UNCOVER-2 and -3 only.

b p≤.05 vs PBO using CMH test stratified by study. Comparisons with ETN included patients enrolled in UNCOVER-2 and UNCOVER-3 only.

c p≤.001 vs ETN using CMH test stratified by study; UNCOVER-2 and UNCOVER-3 only.

d p≤.001, IXE Q4W vs IXE Q2W using CMH test stratified by study.

e p<.001 vs PBO using CMH test stratified by study.

f p<.05, IXE Q4W vs IXE Q2W using CMH test stratified by study.

Efficacy Analysis by Weight Subgroup at Week 60

Data on the efficacy of ixekizumab (PASI 75) at week 60 stratified by weight subgroups are available in Table 2.1

Table 2. UNCOVER-1 and -2: Percentage of Patients Achieving PASI 75 at Week 60 by Weight Subgroups, NRI 1

Weight Subgroup

IXE Q2W/IXE Q4W
N=221
n (%)

<80 kg

60 (81.1)

80 to <100 kg

70 (87.5)

100 kg

54 (80.6)

Abbreviations: IXE Q2W/IXE Q4W = ixekizumab 80 mg every 2 weekly for 12 weeks following a 160 mg starting dose, then ixekizumab 80 mg every 4 weeks during the maintenance period through week 60; NRI = nonresponder imputation; PASI = Psoriasis Area and Severity Index; sPGA = static Physician Global Assessment. 

Note: N=221 represents patients who were responders (achieved sPGA 0,1) to IXE Q2W at week 12 who were rerandomized to IXE Q4W.

Safety Analysis by Weight Subgroups at Week 12

An overview of safety data stratified by weight subgroups through week 12 using the integrated UNCOVER-1, -2, and -3 data is available in Table 3. The incidence of AEs was similar across bodyweight categories within treatment groups.3

Table 3. UNCOVER-1, -2, and -3: Overview of Safety Through Week 12 by Weight Subgroups3

 

<80 kg

80 to <100 kg

100 kg

<80 kg

80 to <100 kg

100 kg

<80 kg

80 to <100 kg

100 kg

<80 kg

80 to <100 kg

100 kg


PBO

ETNa

IXE Q4W

IXE Q2W

N

258

280

251

234

254

251

354

437

368

393

425

349

TEAEs, n (%)

126 (49)

124 (44)

119 (47)

129 (55)b

133 (52)b

137 (55)

226 (64)b

242 (55)b

214 (58)b

235 (60)b

247 (58)b

199 (57)b

SAEs, n (%)

4 (2)

4 (1)

4 (2)

4 (2)

4 (2)

6 (2)

8 (2)

11 (3)

7 (2)

5 (1)

6 (1)

9 (3)

DC due to AE, n (%)

2 (<1)

3 (1)

4 (2)

3 (1)

1 (<1)

5 (2)

10 (3)

11 (3)

3 (<1)

6 (2)

12 (3)

7 (2)

Deaths, n (%)

0

0

0

0

0

0

0

0

0

0

0

0

Abbreviations: AE = adverse event; CMH = Cochran–Mantel–Haenszel; DC = discontinuation; ETN = etanercept 50 mg twice weekly; 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; PBO = placebo; SAE = serious adverse event; TEAE = treatment-emergent adverse event.

a Included in UNCOVER-2 and -3 only.

b p≤.05 vs PBO using CMH test stratified by study. Comparisons with ETN included patients enrolled in UNCOVER-2 and UNCOVER-3 only.

Therapeutic Indication

Ixekizumab is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy.2

References

1. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

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

3. Reich K, Puig L, Mallbris L, et al. The effect of bodyweight on the efficacy and safety of ixekizumab: results from an integrated database of three randomised, controlled phase 3 studies of patients with moderate-to-severe plaque psoriasis. J Eur Acad Dermatol Venereol. 2017;31(7):1196-1207. https://doi.org/10.1111/jdv.14252

4. Puig L. Obesity and psoriasis: body weight and body mass index influence the response to biological treatment. J Eur Acad Dermatol Venereol. 2011;25(9):1007-1011. https://doi.org/10.1111/j.1468-3083.2011.04065.x

Glossary

AE = adverse event

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

sPGA = static Physician Global Assessment

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.

Date of Last Review: April 15, 2020

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