Taltz® (ixekizumab): Genital psoriasisskalor och patientrapporterade resultat.

Clinical Trial Information

• Patients with flexural, inverse, or GP were not excluded from the pivotal ixekizumab phase 3 clinical trials for psoriasis (UNCOVER-1, -2, and -3). However, presence or absence of flexural, inverse, or genital involvement and data regarding severity and improvement were not measured in these trials.¹

IXORA-Q

• The safety and efficacy of ixekizumab in patients with moderate-to-severe GP was evaluated in a phase 3, randomized, double-blind, placebo-controlled clinical trial (IXORA-Q).²

• A brief description of the IXORA-Q trial design is presented in Appendix A: Clinical Trial Brief Description.

• The objective of the clinical trial was to evaluate the efficacy of ixekizumab vs placebo in patients with moderate-to-severe GP during 12 weeks of treatment.²

• Key inclusion criteria included

  • male or female patients at least 18 years of age

  • chronic plaque psoriasis for at least 6 months

  • plaque psoriasis in a non-genital area

  • sPGA-G ≥3

  • sPGA ≥3

  • BSA involvement ≥1%, and

  • failure to respond or intolerance to at least 1 topical therapy for GP (corticosteroids, calcineurin inhibitors, or vitamin D analogues).^2,3

• The primary endpoint was the proportion of patients at week 12 that achieved clear or minimal psoriasis severity in the genital region [sPGA-G (0,1)] including

  • labia majora, labia minora, and perineum in females, and

  • penis, scrotum, and perineum in males.^2,3

• The major secondary endpoints included at week 12, the proportion of patients that

  • achieved overall sPGA (0,1)

  • experienced at least a 3-point improvement in the GPSS score Itch NRS, and

  • achieved a GenPs-SFQ item 2 score of 0 or 1.²

Genital Psoriasis Scales and Outcomes

A significantly greater proportion of patients treated with ixekizumab achieved a reduction in the PROs of severity of genital pain, genital itch, impact of genital psoriasis on sexual activity, and Dermatology Quality of Life Index (DLQI).⁴

• Table 1 explains the scales and specific scale items utilized to measure secondary outcomes in GP response to ixekizumab treatment in the IXORA-Q trial.

• “Sexual Activity” was not limited to sexual intercourse and included activities such as masturbation.⁵

Table 1. IXORA-Q: Genital Psoriasis Scales for Patient-Reported Outcomes

Scale	Question	Minimum Rating	Maximum Rating
GPSS6	Numeric ratings on:  Itch, Pain, Discomfort, Stinging, Burning, Redness, Scaling, and Cracking Also includes a total score (range 0-80)	0, “none”	10, “worst imaginable”
GenPs-SFQ item 27	“In the past week, how often did your genital psoriasis limit the frequency of your sexual activity?”	0, “never”	4, “always”
DLQI item 95	“In the past week, how much has your skin caused any sexual difficulties?”	0, “not at all”	3, “very much”
GPSIS-avoidance5	“In the past week, how often did you avoid sexual activity because of your genital psoriasis symptoms?”	1, “never”	5, “always”
GPSIS-impact5	“In the past week, how would you rate the level (degree) of worsening of your genital psoriasis symptoms during or following sexual activity?”	1, “very low or not at all”	5, “very high”

Abbreviations: DLQI = Dermatology Life Quality Index; GenPs-SFQ = Genital Psoriasis Sexual Frequency Questionnaire; GPSIS = Genital Psoriasis Sexual Impact Scale; GPSS = Genital Psoriasis Symptom Scale.
NOTE: “Sexual Activity” was not limited to sexual intercourse and includes activities such as masturbation.

Genital Psoriasis Symptom Scale

• Ixekizumab treatment led to a significant improvement in GPSS total score vs placebo within 1 week and through 12 weeks as shown in Figure 1.⁵

• Ixekizumab was superior to placebo in improving all individual GPSS components within 1 week and through 12 weeks.⁸

Figure 1. IXORA-Q: Total GPSS Score Change from Baseline Through Week 12, ITT Population, MMRM⁵

Abbreviations: GPSS = Genital Psoriasis Symptom Scale; ITT = intent to treat; IXE Q2W = 80mg ixekizumab every 2 weeks; LSM = least squares mean; MMRM = mixed models repeated measure analysis; PBO = placebo.
^‡ p<.001 vs. PBO

Genital Psoriasis Sexual Frequency Questionnaire

Significantly more patients treated with ixekizumab achieved GenPs-SFQ item 2 score (0,1) (indicating GP never or rarely limited sexual activity) at week 12 for patients with a GenPs-SFQ item 2 score of ≥2 at baseline (see Figure 2).² 

Figure 2. IXORA-Q: GenPS-SFQ Item 2 Score (0,1) Through 12 Weeks, NRI, ITT Population with Baseline GenPs-SFQ Item 2 Score of ≥2⁹

Abbreviations: GenPs-SFQ = Genital Psoriasis Sexual Frequency Questionnaire; ITT = intent to treat; IXE Q2W = 80mg ixekizumab every 2 weeks; NRI = non-responder imputation; PBO = placebo.
* p<.05; ^† p<.01; ^‡ p<.001

Dermatology Life Quality Index Item 9

• Patients receiving ixekizumab showed significant improvement in DLQI item 9 score (0,1) from week 2 through week 12.⁵

• As shown in Figure 3, response rates for patients achieving DLQI item 9 scores of 0 or 1 at week 12 persisted through 52 weeks of treatment with ixekizumab.¹⁰

Note that different dosing regimens, including unapproved doses, are included in this response. Please refer to Taltz summary of product characteristics for full prescribing information.

Figure 3. IXORA-Q: DLQI Item 9 Score (0,1) at Weeks 12 and 52, NRI¹⁰

Abbreviations: DLQI = Dermatology Life Quality Index; IXE = ixekizumab; NRI = nonresponder imputation; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks.

Genital Psoriasis Sexual Impact Scale

• Patients receiving ixekizumab showed significant improvement in GPSIS-avoidance (1,2) from week 4 through week 12.^5,9

• Among patients who were sexually active, there was significant improvement in GPSIS-impact (1,2) at weeks 2, 4, and 8 but not week 12.⁵

• As shown in Figure 4, response rates for patients achieving avoidance and impact subscale scores of 1 or 2 at week 12 persisted through 52 weeks of treatment with ixekizumab.¹⁰

Note that different dosing regimens, including unapproved doses, are included in this response. Please refer to Taltz summary of product characteristics for full prescribing information.

Figure 4. IXORA-Q: GPSIS Avoidance and Impact Subscale Scores (1,2) at Weeks 12 and 52, Patients With Baseline Scores ≥3, NRI¹⁰

Abbreviations: GPSIS = Genital Psoriasis Sexual Impact Scale; IXE = ixekizumab; NRI = nonresponder imputation; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks.

Therapeutic Indication

Ixekizumab is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy.⁴

References

1. Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375(4):345-356. http://dx.doi.org/10.1056/NEJMoa1512711

2. Ryan C, Menter A, Guenther L, et al. Efficacy and safety of ixekizumab in a randomized, double-blinded, placebo-controlled phase IIIb study of patients with moderate-to-severe genital psoriasis. Br J Dermatol. 2018;179(4):844-852. http://dx.doi.org/10.1111/bjd.16736

3. Ryan C, Menter A, Guenther L, et al. Efficacy and safety of ixekizumab in a randomized, double-blinded, placebo-controlled, phase 3b clinical trial in patients with moderate-to-severe genital psoriasis. 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. Yosipovitch G, Foley P, Ryan C, et al. Ixekizumab improved patient-reported genital psoriasis symptoms and impact of symptoms on sexual activity vs placebo in a randomized, double-blind study. J Sex Med. 2018;15(11):1645-1652. http://dx.doi.org/10.1016/j.jsxm.2018.09.004

6. Gottlieb AB, Kirby B, Ryan C, et al. The development of a patient-reported outcome measure for assessment of genital psoriasis symptoms: The genital psoriasis symptoms scale (GPSS). Dermatol Ther (Heidelb). 2018;8(1):45-56. http://dx.doi.org/10.1007/s13555-017-0213-2

7. Gottlieb AB, Kirby B, Ryan C, et al. The development of the genital psoriasis sexual frequency questionnaire (GenPs-SFQ) to assess the impact of genital psoriasis on sexual health. Dermatol Ther (Heidelb). 2018;8(1):33-44. http://dx.doi.org/10.1007/s13555-017-0212-3

8. Yosipovitch G, Foley P, Burge R, et al. Ixekizumab provides rapid and greater improvement of the symptoms of genital psoriasis compared to placebo in a randomized, double-blind, phase 3b clinical trial. J Am Acad Dermatol. 2018;79(3):AB174. https://doi.org/10.1016/j.jaad.2018.05.709

9. Cather JC, Meeuwis K, Burge R, et al. Ixekizumab Provides greater improvement versus placebo on the impact of genital psoriasis on sexual activity for patients with moderate-to-severe genital psoriasis in a randomized, double-blind phase 3b clinical trial. Poster presented at: 76th Congress of the American Academy of Dermatology; February 16-20, 2018: San Diego, CA. https://server.aad.org/eposters/Submissions/getFile.aspx?id=5935&type=sub

10. Ryan C, Foley P, Burge R, et al. Persistence of improvement in sexual impact associated with moderate-to-severe genital psoriasis for up to 52 weeks of treatment with ixekizumab. Poster presented at: 28th Annual Meeting of the European Academy of Dermatology and Venereology; October 9-13, 2019; Madrid, Spain.

11. Guenther L, Potts Bleakman A, Weisman J, et al. Persistent clinical improvement in genital psoriasis through one year of treatment with ixekizumab: results of a randomized, placebo-controlled phase 3 clinical trial in patients with moderate-to-severe genital psoriasis (IXORA-Q). Poster presented at: 77th Annual Meeting of the American Academy of Dermatology; March 1-5, 2019; Washington, D.C.

Glossary

DLQI = Dermatology Life Quality Index

GenPs-SFQ = genital psoriasis sexual frequency questionnaire

GP = genital psoriasis

GPSIS = Genital Psoriasis Sexual Impact Scale

GPSS = genital psoriasis symptom scale

NRS = numeric rating scale

sPGA = static Physician Global Assessment

sPGA-G = static Physician Global Assessment of Genitalia

Appendix A: Clinical Trial Brief Description

Figure 5. IXORA-Q: Study Design¹¹

Abbreviations: IXE = ixekizumab; IXE Q2W = ixekizumab every 2 weeks; IXE Q4W = ixekizumab every 4 weeks; PBO = placebo.

^a Given as two 80 mg subcutaneous injections at week 0. Patients assigned to PBO received 2 subcutaneous injections of PBO at week 0.

^b Option to step up to IXE Q2W at weeks 24, 28, and 40.

^c At week 12, patients in the IXE Q2W group received 1 dose of ixekizumab 80 mg and 1 dose of placebo; patients in the PBO group received 2 doses of ixekizumab 80 mg.