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DOI: 10.1111/jdv.12996

ORIGINAL ARTICLE

Improvement of scalp and nail lesions with ixekizumab in a phase 2 trial in patients with chronic plaque psoriasis R.G. Langley,1,* P. Rich,2 A. Menter,3 G. Krueger,4 O. Goldblum,5 Y. Dutronc,5 B. Zhu,5 H. Wei,5 G.S. Cameron,5 M.P. Heffernan5 1

Division of Clinical Dermatology and Cutaneous Science, Department of Medicine, Dalhousie University, Halifax, NS, Canada Department of Dermatology, Oregon Health & Science University School of Medicine, Portland, OR, USA 3 Department of Dermatology, University of Texas Southwestern Medical Center Southwestern Medical School, Dallas, TX, USA 4 Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT, USA 5 Eli Lilly and Company, Indianapolis, IN, USA *Correspondence: R.G. Langley. E-mail: [email protected] 2

Abstract Background Scalp and nail psoriasis have a major impact on quality of life and are traditionally resistant to therapy. Ixekizumab is a monoclonal antibody that targets IL-17A, a key cytokine in psoriasis pathogenesis. Objective Changes in nail and scalp psoriasis associated with ixekizumab treatment were evaluated in a post hoc analysis of a phase 2 study comprising a 20-week randomized, placebo-controlled (RCT) period and 48 weeks of an open-label extension (OLE) period. Methods There were 142 patients with moderate-to-severe plaque psoriasis at baseline of the RCT. Patients were randomized to receive placebo, 10, 25, 75 or 150 mg of ixekizumab injected subcutaneously at weeks 0, 2, 4, 8, 12 and 16. In the OLE, all patients received 120 mg ixekizumab every 4 weeks. Nail Psoriasis Severity Index (NAPSI) and Psoriasis Scalp Severity Index (PSSI) were used to evaluate nail and scalp psoriasis respectively. Fifty-eight (41.0%) patients had nail psoriasis (NAPSI > 0) and 105 (74.0%) had scalp psoriasis (PSSI > 0) at baseline; these cases were evaluated for the present analyses. Results At RCT week 20, patients with scalp psoriasis in the 25-, 75- and 150-mg groups had significant mean change and percent improvement from baseline PSSI of (82.2%; P < 0.001) respectively compared to

16.3 (75.3%; P = 0.001),

11.6 (83.7%; P = 0.001) and

18.2

6.0 (18.8%) in placebo. Patients with nail psoriasis in the 75- and 150-mg

groups had significant improvements from baseline NAPSI of

26.3 (63.8%; P = 0.003) and

23.1 (52.6%; P = 0.009)

respectively compared to 0.4 ( 1.7%) in placebo. By OLE week 48, 78.0% of patients with scalp psoriasis and 51.0% of patients with nail psoriasis experienced complete resolution of lesions (PSSI = 0 or NAPSI = 0). Conclusions Ixekizumab monotherapy improved scalp psoriasis quickly with maintenance of clinical response and complete resolution of plaques in the majority of patients. Additionally, over 50.0% of patients with nail psoriasis experienced complete resolution of nail lesions by OLE week 48. Received: 25 September 2014; Accepted: 7 January 2015 Clinical Trials.gov number: NCT01107457.

Conflicts of interest RGL has been an Investigator, served on the Scientific Advisory Board or speaker for Abbvie, Eli Lilly and Company, Celgene, Amgen, and Centocor. PR has been reimbursed by Abbvie, Amgen, Celgene, Eli Lilly and Company, Janssen, Merck, Novartis, and Pfizer for acting as primary investigator in psoriatic studies. AM has served as an advisory board member and/or consultant and/or investigator and/or speaker and/or received compensation in the form of grants and/ or honoraria from AbbVie, Allergan, Amgen, ApoPharma, Boehringer Ingelheim, Celgene, Convoy Therapeutics, Inc., Eli Lilly and Company, Genentech, Janssen Biotech, Inc., LEO Pharma, Merck, Novartis, Pfizer, Symbio/Maruho, Syntrix, Wyeth, and XenoPort. GGK has received honoraria as Chair of DMSB for Tofacitinib for psoriasis. OG is an employee of Lilly USA. YD is an employee of Eli Lilly and Company. BZ is an employee of and owns stock in Eli Lilly and Company. HW is an employee of Eli Lilly and Company. GSC is an employee of and owns stock in Eli Lilly and Company. MPH was employed by Eli Lilly and company when this manuscript was being drafted. MPH was employed by Eli Lilly and Company during the drafting of this manuscript.

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Funding sources This study was sponsored by Eli Lilly and Company.

Introduction Psoriasis is an inflammatory/immune-mediated condition characterized by pruritus and inflamed, thickened, scaly plaques that vary in location and percent of body area affected. An estimated 17% of psoriasis patients have moderate-to-severe psoriasis.1 Psoriasis in more visible locations, such as the scalp and nails, has a disproportionate burden and more profound impact on quality of life (QOL).2,3 Several recent reports suggest that among patients with psoriasis, 41% to 77% have nail psoriasis.2,4–6 In addition to cosmetic concerns, many patients with nail psoriasis have reported associated pain, interference with daily activities and work productivity,7 and a great effect of their disease on health-related QOL.2 As many as 80% of psoriasis patients have scalp psoriasis,8 which is also known to impact QOL, particularly as it pertains to persistent itch and lesion visibility.3,9 Both scalp and nail psoriasis lesions are traditionally difficult to treat effectively with topical medications, phototherapy and even systemic oral medications.10,11 For nail psoriasis, this could be due, at least in part, to the limited flux of topically applied drugs through the nail plate and therewith a slower response time, which may lead to poor adherence.12 Treatment of scalp psoriasis is also difficult with poor adherence to therapy.11 Biologic therapies have shown promise in treating psoriasis of the scalp and nails.4,8,10,13–16 Ixekizumab is a fully humanized monoclonal antibody targeting IL-17A, and in a phase 2 trial, ixekizumab significantly improved psoriasis over 20 weeks of randomized placebo-controlled therapy.17 Here, we report the impact of ixekizumab monotherapy on nail and scalp psoriasis during the randomized, placebo-controlled (RCT) period and nearly 1 year of open-label extension (OLE) treatment in this trial.

Methods Patients and study design

This is a post hoc analysis of data from a phase 2 clinical trial in patients with moderate-to-severe plaque psoriasis that included a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging (RCT) period and an OLE period. Full details of the study design, inclusion and exclusion criteria, patient population and primary safety and efficacy results have been described previously.17,18 Briefly, in the RCT, 142 patients received subcutaneous injections of 10, 25, 75 or 150 mg of ixekizumab or placebo at 0, 2, 4, 8, 12 and 16 weeks of study I1F-MC-RHAJ (NCT01107457). At week 20, patients who had not achieved a PASI 75 were eligible to enter directly into the OLE. Patients who had achieved a PASI 75 at week 20 entered a

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treatment-free period, where they were monitored every 4 weeks until the clinical response dropped below a PASI 75, or week 32, at which time they were eligible to enter the OLE. In the OLE, patients received 120 mg of ixekizumab subcutaneously every 4 weeks. This interim analysis included data for patients who were followed up to 52 weeks after entering the OLE. During the RCT, supportive treatment included as-needed topical moisturizers or emollients, bath oils, oatmeal bath preparations, topical salicylic acid preparations. Additionally, as-needed class 6 [mild] or 7 [least potent] topical steroids were permitted for use limited to the face, axilla and/or genitalia. During the OLE, at the investigator’s discretion, more potent topical steroids could be used as medically required to treat a flare. These topical medications were not to be used within approximately 24 h prior to visits evaluating the PASI. The study protocol was approved by the local Institutional Review Boards at each site in accordance with the Declaration of Helsinki. All patients participating in the study provided written informed consent. Assessments

Nail Psoriasis Severity Index (NAPSI) scores are composite scores of physician assessment of each nail for psoriasis features in nail bed and nail matrix (range: 0–160).19 Psoriasis Scalp Severity Index (PSSI) scores are the sum of physician-assessed scores for severity of erythema, induration and desquamation multiplied by the extent of scalp involvement (range: 0–72).20 In the RCT, NAPSI and PSSI information was collected at weeks 0, 1, 2, 4, 6, 8, 12, 16 and 20. PSSI and NAPSI information was collected at weeks 0, 12, 24, 36 and 48 of the OLE. Statistical analyses

The analyses in this study include only patients with baseline scalp psoriasis (PSSI > 0) for PSSI and only patients with baseline nail psoriasis (NAPSI > 0) for NAPSI. Comparisons of ixekizumab groups to placebo in the RCT for continuous variables were made using analysis of variance (ANOVA) with adjustment for baseline PSSI in the scalp psoriasis group. Comparisons on changes in PSSI and NAPSI from baseline were conducted using t-tests. Significant differences from placebo were defined as P < 0.05. NAPSI and PSSI score means and standard deviations (SD) were reported for placebo, 10-, 25-, 75- and 150mg ixekizumab groups for weeks 0–20 of the RCT. For the OLE, during which all patients were treated with 120 mg ixekizumab, two groups were considered: the group of patients initially assigned to placebo (PBO-IXE) and the group of patients that were randomized to one of the 4 doses of ixekizumab (IXE-IXE). Proportions of patients achieving complete resolution of nail and

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Table 1 Nail Psoriasis Severity Index scores at weeks 0, 12 and 20 of RCT and weeks 0, 24 and 48 of OLE

Week 0 (baseline) Week 12

Week 20

Randomized, placeboControlled Trial (RCT)

Placebo (n = 15)

NAPSI (SD)

39.3 (27.2)

41.9 (44.8)

34.9 (37.7)

NAPSI (SD)

40.9 (32.6)

37.0 (43.1)

31.4 (38.5)

NAPSI change from BL

1.6

% Improvement NAPSI

6.8

% Patients with NAPSI = 0

0

NAPSI (SD)

Week 24

Week 48

Ixekizumab 25 mg (n = 10)

4.9NS

39.7 (29.4)

3.5NS

Ixekizumab 75 mg (n = 10) 45.0 (46.9) 29.0 (38.7)

26.4 (27.6)

16.0**

20.1***

24.0

57.1

49.3

10.0

30.0

20.0

29.4 (43.0)

18.7 (25.8)

23.4 (21.9)

26.3**

23.1**

63.8

52.6

30.0 Total (n = 51)

20.0

30.6 (33.9) 11.3NS

% Improvement NAPSI

1.7

7.2 0 PBO-IXE (n = 12) 36.4 (30.4)NS

5.5NS 34.9 30.0 IXE-IXE (n = 39) 23.1 (32.9)†

26.0 (32.6)†

NAPSI change from BL

2.7

20.0

15.0

% Improvement NAPSI

6.6

44.0

32.9

% Patients with NAPSI = 0

0

25.6

20.0

NAPSI (SD)

13.9 (27.7)†

12.7 (25.0)†

NAPSI change from BL

26.3

29.3

28.6

% Improvement NAPSI

79.7

77.5

78.0

% Patients with NAPSI = 0

41.7

43.6

43.1

NAPSI (SD) NAPSI change from BL

46.5 (51.7)

0

0.4

NAPSI (SD)

Ixekizumab 150 mg (n = 10)

14.3

NAPSI change from BL

% Patients with NAPSI = 0 0 OLE: All patients received 120 mg Q4W Week 0

Ixekizumab 10 mg (n = 13)

9.1 (13.3)†

3. 8 (7.8)† 31.7

10.6 (20.7)† 32.5

9.0 (18.7)† 32.3

% Improvement NAPSI

92.4

75.4

79.4

% Patients with NAPSI = 0

58.3

48.7

51.0

*P < 0.05, **P < 0.01 and ***P < 0.001. Significant differences from placebo using ANOVA. †Significantly different from baseline using within-group t-test at P < 0.001 (OLE). NS Not significantly different from placebo (RCT) or baseline (OLE). Mean scores are reported for NAPSI, NAPSI change from BL and percent improvement in NAPSI. Missing values were imputed using the last observation carried forward and all changes and percent improvements are based on comparison to baseline of RCT. ANOVA, analysis of variance; BL, baseline; IXE-IXE, RCT ixekizumab-OLE ixekizumab; NAPSI, Nail Psoriasis Severity Index; OLE, open-label extension; PBO-IXE, RCT placebo-OLE ixekizumab; Q4W, every 4 weeks.

scalp lesions, as defined by NAPSI = 0 and PSSI = 0 respectively were also calculated. Missing values were imputed using last observation carried forward (LOCF).

Results Nail psoriasis in the RCT

In this aspect of the RCT, 58 (41.0%) of the 142 randomized patients had nail psoriasis at baseline and had a mean (SD) baseline NAPSI score of 41.3 (40.2). At week 20, patients in the 75-mg [mean change: 26.3 (percent improvement: 63.8%; P = 0.003)] and 150-mg [ 23.1 (52.6%); P = 0.009] ixekizumab dose groups had significant improvement from baseline NAPSI compared to placebo [0.4 ( 1.7%)] (Table 1 and Fig. 1a). The proportions of patients who achieved complete resolution of nail psoriasis lesions at week 20 of the RCT in the placebo, 10-, 25, 75- and 150-mg ixekizumab dose groups were 0%, 0%, 30.0%, 30.0% and 20.0% respectively (Table 1 and Fig. 1c).

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Nail psoriasis in the OLE

Fifty-one patients with baseline nail psoriasis entered the OLE. At the start of the OLE, the mean (SD) NAPSI was 36.4 (30.4) for patients in the PBO-IXE group and 23.1 (32.9) for patients in the IXE-IXE group. By week 48 of the OLE, there were significant changes in NAPSI from baseline in patients in both the PBO-IXE [ 31.7 (92.4%); P < 0.001] and IXE-IXE [ 32.5 (75.4%); P < 0.001] groups (Table 1 and Fig. 1b). Proportions of patients achieving complete resolution of nail psoriasis lesions in the PBO-IXE and IXE-IXE groups were 58.3% and 48.7% respectively at week 48 (Table 1 and Fig. 1d). Scalp psoriasis in the RCT

Among the 105 (74%) patients with scalp psoriasis at baseline, the mean (SD) baseline PSSI score was 18.7 (12.8). Table 2 and Fig. 2 provide a comparison of the responses and the proportions of patients who achieved complete resolution of scalp psoriasis plaques at week 20 of the RCT period in the placebo,

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(a)

(b)

(c)

(d)

Figure 1 (a) Mean percent improvement in NAPSI from baseline through week 20 of the RCT. Significant changes from baseline NAPSI (P < 0.05) compared to placebo were observed at week 2 in the 150-mg treatment group and were maintained through week 20 of the RCT. Significant changes from baseline NAPSI (P < 0.05) compared to placebo were observed only at week 2 of the RCT for the 25-mg group and at weeks 2, 4, 8, 12 and 20 of the RCT for the 75-mg treatment groups. (b) Mean percent improvement from baseline of the RCT from weeks 0 to 48 of the OLE. Proportion of patients with complete resolution of nail psoriasis lesions (NAPSI = 0) in the (c) RCT and (d) OLE. Missing data were imputed using the last observation carried forward. IXE, ixekizumab; PBO, placebo; PBO-IXE, RCT placebo-OLE ixekizumab; IXE-IXE, RCT ixekizumab-OLE ixekizumab.

10-, 25-, 75- and 150-mg ixekizumab dose groups. Patients in the 150-mg treatment group experienced significant improvements from baseline PSSI [ 8.7 (37.5%); P = 0.003] compared to placebo [ 2.4 (10.9%)] as early as week 1 (Fig. 2a). By week 4, patients in the 25-mg [ 12.3 (66.6%); P = 0.03], 75-mg [ 9.7 (77.4%); P = 0.01] and 150-mg [ 17.9 (86.2%); P < 0.001] ixekizumab dose groups had significant improvements from baseline PSSI compared to placebo [6.4 (26.9%)]. These changes were maintained or improved through week 20; patients in the 25-, 75- and 150-mg ixekizumab dose groups had mean changes from baseline PSSI of 16.3 (percent improvement: 75.3%; P = 0.001), 11.6 (83.7%; P = 0.001) and 18.2 (82.2%; P < 0.001), respectively vs. placebo [ 6.0 (18.8%)] (Table 2 and Fig. 2a). Additionally, the proportions of patients achieving complete resolution of scalp psoriasis plaques at week

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20 of the RCT were 10.0% in placebo group and 38.1%, 58.3%, 66.7%, 86.4% in the 10-, 25-, 75- and 150-mg ixekizumab treatment groups respectively (Table 2 and Fig. 2c). Scalp psoriasis in the OLE

Ninety-one patients with baseline scalp psoriasis entered the OLE. At the start of the OLE, the 16 patients in the PBO-IXE group had a mean (SD) PSSI score of 13.0 (11.1), whereas the 75 patients in the IXE-IXE group had a mean (SD) PSSI score of 6.1 (8.2). At week 24 of the OLE, the reduction in PSSI and percent improvement were statistically significant from baseline (RCT) PSSI for patients in both PBO-IXE [ 19.7 (95.3%); P < 0.001] and IXE-IXE [ 17.8 (90.5%); P < 0.001] groups (Fig. 2b). The statistically significant improvements from baseline PSSI were maintained through week 48 of the OLE for both

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Table 2 Psoriasis Scalp Severity Index scores at weeks 0, 12 and 20 of RCT and weeks 0, 24 and 48 of OLE Randomized, placebo-controlled trial (RCT)

Placebo (n = 20)

Ixekizumab 10 mg (n = 21)

Ixekizumab 25 mg (n = 24)

Ixekizumab 75 mg (n = 18)

Week 0 (baseline)

PSSI (SD)

18.8 (14.1)

19.5 (14.6)

20.5 (13.7)

13.8 (8.7)

Week 12

PSSI (SD)

11.8 (13.4)

8.9 (10.4)

3.8 (7.8)

1.3 (3.6)

PSSI change from BL

Week 20

7.1

1.8 (4.2) 18.3***

30.5

43.4

87.1

94.8

84.8

15.0

38.1

58.3

83.3

72.7

PSSI (SD)

12.8 (12.8)

11.1 (12.2)

6.0 18.8

% Patients with PSSI = 0 10.0 OLE: All patients received 120 mg Q4W PSSI (SD) PSSI change from BL % Improvement in PSSI % Patients with PSSI = 0 PSSI (SD) PSSI change from BL

Week 48

12.5***

% Patients with PSSI = 0

% Improvement in PSSI

Week 24

16.7***

20.1 (11.7)

% Improvement in PSSI

PSSI change from BL

Week 0

10.7NS

Ixekizumab 150 mg (n = 22)

8.4NS 16.5

4.2 (8.0)

7.4

11.6**

75.3

38.1 58.3 PBO-IXE (n = 16) 13.0 (11.1)‡

2.2 (4.0)

16.3**

83.7 66.7 IXE-IXE (n = 75) 6.1 (8.2)† 13.0

1.9 (5.1) 18.2*** 82.2 86.4 Total (n = 91) 7.3 (9.1)† 12.0

28.1

55.5

50.7

6.3

41.3

35.2

0.8 (2.5)† 19.7

1.2 (4.0)† 17.8

1.2 (3.7)† 18.1

% Improvement in PSSI

95.3

90.5

91.3

% Patients with PSSI = 0

87.5

85.3

85.7

PSSI (SD) PSSI change from BL

0.4 (0.9)† 20.1

2.0 (5.0)† 17.0

1.7 (4.6)† 17.6

% Improvement in PSSI

98.1

87.5

89.3

% Patients with PSSI = 0

81.3

77.3

78.0

*P < 0.05, **P < 0.01 and ***P < 0.001. Significant differences from placebo using ANCOVA adjusted for baseline PSSI. ‡P < 0.05 and † P < 0.001. Significantly different from baseline using within-group t-test (OLE). NS Not significantly different from placebo (RCT) or baseline (OLE). Mean scores are reported for PSSI, PSSI change from BL and percent improvement in PSSI. Missing values were imputed using last observation carried forward (LOCF) and all changes and percent improvements are based on comparison to baseline of RCT. ANCOVA, analysis of covariance; BL, baseline; IXE-IXE, RCT ixekizumab-OLE ixekizumab; OLE, open-label extension; PBO-IXE, RCT placebo-OLE ixekizumab; PSSI, Psoriasis Scalp Severity Index; Q4W, every 4 weeks.

the PBO-IXE [ 20.1 (98.1%); P < 0.001] and IXE-IXE [ 17.0 (87.5%); P < 0.001] groups. At week 48 of the OLE, proportions of patients with complete resolution of scalp psoriasis plaques in the PBO-IXE and the IXE-IXE groups were 81.3% and 77.3% respectively (Table 2 and Fig. 2d).

Discussion In this post hoc analysis from a phase 2 study of ixekizumab, substantial, sustained and early statistically significant improvements in scalp and to a slightly lesser degree nail psoriasis were observed during the 20-week RCT and over 1 year of open-label treatment. Improvement of scalp lesions was rapid with significant differences vs. placebo observed as early as 1 week following the first dose in patients treated with the 150-mg dose of ixekizumab. Nail improvements were initially slow, but improvements continued out to week 48 in the OLE. The slower improvement in nails was anticipated due to the more gradual rate at which nail grow. By the end of the OLE, complete resolution of nail psoriasis lesions was experienced by half the patients

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with baseline nail psoriasis and complete resolution of scalp psoriasis plaques in almost 80% of patients with baseline scalp psoriasis. Although no cross-study comparisons to ixekizumab were available, the effects of ixekizumab on nail and scalp psoriasis compare favourably with currently approved biologic agents.13,21–27 There is a considerable medical need for better treatments of nail and scalp psoriasis. Nail psoriasis has historically been challenging to treat due to anatomic factors in drug delivery to the nail unit and slow growth of nails resulting in delayed improvement and resolution of symptoms in psoriatic nails compared to skin.13 Improving, or ideally clearing, nail psoriasis is an important goal, given the negative impact of nail disease on QOL. In a large survey of over 1300 patients with nail psoriasis, roughly half reported pain and restriction of activities of daily life, and nearly all patients reported concerns about the cosmetic appearance of their nails.8 Scalp psoriasis has also been challenging to treat, particularly with topical treatments, given the greater difficulty in application and reduced

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(a)

(b)

(c)

(d)

Figure 2 (a) Mean percent improvement in PSSI from baseline through week 20 of the RCT. Significant changes from baseline PSSI (P < 0.05) compared to placebo were observed at week 1 in the 150-mg treatment group and were maintained through week 20 of the RCT. Significant changes from baseline PSSI (P < 0.05) compared to placebo were observed at week 4 in the 25- and 75-mg treatment groups and were maintained through week 20 of the RCT. (b) Mean percent improvement from baseline of the RCT from weeks 0 to 48 of the OLE. Proportion of patients with complete resolution of scalp psoriasis plaques (PSSI = 0) in the (c) RCT and (d) OLE. Missing data were imputed using the last observation carried forward. IXE, ixekizumab; PBO, placebo; PBO-IXE, RCT placebo-OLE ixekizumab; IXEIXE, RCT ixekizumab-OLE ixekizumab.

absorption compared to areas of the body with little to no hair coverage.12 Additionally, associations with psychosocial distress were found in a survey-based study evaluating over 900 patients with scalp psoriasis, where patients reported that itching and scaling were the most common and most distressing symptoms.10 Prior studies of the effects of biologic agents on nail psoriasis have varied substantially in study duration, population size and study design, making comparisons difficult.4,15,16,27,28 In addition, some studies have chosen scoring systems other than NAPSI to assess nail psoriasis.16 Overall, mean improvements in NAPSI observed over 12–24 weeks of treatment with anti-TNF agents ranged from 50%21,23,27 and 51% to‒68% during extended periods (50–54 weeks) of treatment.22,24 Patients with nail

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psoriasis treated with the higher dose (90 mg) of an anti-IL-12/ 23 antibody, ustekinumab, had 24.9% and 48.7% improvement from baseline NAPSI by weeks 12 and 24 respectively.28 Another agent targeting IL-17A has also been shown to be effective in treatment of nail psoriasis; however, this study evaluated nail disease using only a composite finger nail score, rather than NAPSI score.16 In our study, assessments of both finger and toe nails were included in the NAPSI score, and toe nails are known to grow at a slower rate than finger nails.29 Generally, these results are consistent with our finding of more pronounced results following long-term therapy. Studies of biologics in treating scalp psoriasis are more limited; ixekizumab at doses of 75 and 150 mg appeared to show comparable results to those biologics which have been assessed

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for scalp psoriasis treatment. Significant improvements in PSSI were observed in patients with scalp psoriasis in a randomized, double-blind, placebo-controlled trial of etanercept, with mean percent improvement from baseline PSSI of 59.6% and 86.8% at weeks 4 and 12, respectively, in the etanercept group, compared to 15.6% and 20.4% at weeks 4 and 12 respectively, in the placebo group.13 Similarly, in a 16-week study of adalimumab for treatment of moderate-to-severe psoriasis, patients with scalp psoriasis experienced mean percent improvement in PSSI of 77.2% by week 16.26 Our study is one of the few to examine the role of a biologic on scalp psoriasis and the first to study both nail and scalp psoriasis in response to an anti-IL-17A antibody over the course of 48 weeks using the objective and reproducible NAPSI and PSSI scoring systems. This study is limited by relatively small sample size and requires validation in a larger study. While this study is strengthened by long-term follow-up in the OLE, it also lacks a comparator group in the long-term period. Thus, it is difficult to say with certainty that the changes observed were solely due to ixekizumab treatment. While this study only includes patients with overall moderate-to-severe psoriasis, there was a wide range in baseline nail and scalp lesion severity, making it possible that complete resolution for some patients was facilitated by milder disease.

Conclusions In conclusion, ixekizumab treatment resulted in rapid scalp psoriasis improvements that were maintained through 48 weeks of open-label ixekizumab treatment. Improvements in nail psoriasis lesions were shown to be slower than scalp lesions, but sustained and significant responses to ixekizumab treatment were noted through week 48 in the OLE. Finally, a substantial proportion of patients treated with ixekizumab in the OLE enjoyed a complete resolution of both nail and scalp psoriasis lesions. Phase 3 studies with clinically relevant doses (80 mg) in a larger patient population are necessary to validate these findings. These studies are currently in progress.

Acknowledgements The authors thank Xingxing Wu, MS (InVentiv Health Clinical, Princeton, NJ) for assistance with data analysis, and David S. Shrom, PhD (Eli Lilly and Company, Indianapolis, IN) and Bridget Charbonneau, PhD (Eli Lilly and Company, Indianapolis, IN) for assistance with manuscript preparation and submission.

References 1 Kurd SK, Gelfand JM. The prevalence of previously diagnosed and undiagnosed psoriasis in US adults: results from NHANES 2003–2004. J Am Acad Dermatol 2009; 60: 218–224. 2 Klaassen KM, de van Kerkhof PC, Pasch MC. Nail psoriasis, the unknown burden of disease. J Eur Acad Dermatol Venereol 2014; 28: 1690–1695. 3 van de Kerkhof PC, Franssen ME. Psoriasis of the scalp. Diagnosis and management. Am J Clin Dermatol 2001; 2: 159–165.

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