SUMMARY

• The company cannot recommend any practices, procedures or usage that deviate from the approved labeling.
• There is published literature describing the use of STELARA in patients with nail psoriasis (PsO).^1-7

Clinical data

Phase 3 Studies

AMAGINE - 2/3

Elewski et al (2022)⁷ reported post-hoc efficacy data from two phase 3 randomized, double-blind, placebo and active comparator arm studies examining the safety and efficacy of STELARA and brodalumab in patients with moderate-to-severe plaque PsO of the nail through week 52.

Study Design/Methods

• Adult patients (18-75 years of age) with a moderate-to-severe plaque psoriasis diagnoses ≥6 months before the first dose of study drug, a body surface area (BSA) involvement of ≥10%, a psoriasis area and severity index (PASI) of ≥12, and a static physician’s global assessment (PGA) score of ≥3 at screening and baseline were included in the study.⁷
• Nail efficacy was measured using the nail psoriasis severity index (NAPSI; range, 0-32).
• NAPSI was calculated by assessing the presence of eight clinical features of nail PsO (pitting, leukonychia, red spots in lunula, nail plate crumbling, oil drop discoloration, onycholysis, nail bed hyperkeratosis, and splinter hemorrhages) in each of the four quadrants of the most affected nail.
• The post-hoc analysis included patients with a baseline NAPSI of ≥6 who received continuous STELARA (45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg; q12w) or brodalumab treatment (210 mg; q2w) through week 52.
• NAPSI outcomes were analyzed using as observed data.^7,8
• All P-values were nominal without multiplicity adjustment.⁷

Results

• Mean NAPSI, percentage of responders with a NAPSI of 0, and percent improvement rates from baseline NAPSI, are reported for both STELARA and brodalumab in Table: Post-hoc As Observed AMAGINE – 2/3 NAPSI Results through Week 52.⁷

IXORA-S

Wasel et al (2020)¹ reported post-hoc efficacy data from a phase 3b, randomized, multicenter double-blind, head-to-head study examining the safety and efficacy of STELARA and ixekizumab in patients with moderate-to-severe plaque PsO and nail PsO.

Study Design/Methods

• Adult patients (≥18 years of age) with chronic plaque psoriasis for ≥6 months, had a PASI score ≥10 and had previously failed or had a contraindication or intolerability to at least one systemic therapy (including ciclosporin, methotrexate and phototherapy) were included.⁹
• Patients with presence of nonplaque psoriasis, a contraindication for STELARA, or prior treatment with STELARA, ixekizumab or any other IL‐17 or IL‐12/23 antagonists were excluded.⁹
• Eligible patients were randomized in a 1:1 ratio to one the following treatment arms:¹
  • Ixekizumab 160-mg starting dose administered as two 80-mg injections, then 80 mg every 2 weeks for 12 weeks, followed by 80 mg every 4 weeks (N=136).
  • STELARA 45 mg or 90 mg (weight-based dosing) administered at weeks 0, 4 and every 12 weeks thereafter (N=166).
• The proportion of patients achieving NAPSI score of 0 (complete resolution), a NAPSI score change from baseline and correlations in PASI and NAPSI improvement over 52 weeks were examined.
• Categorical data for treatment groups were assessed via logistic regression, with treatment, weight (≤100 kg, >100 kg), and geographic region (Western European Union [EU], Eastern EU, North America) as factors.
  • Missing data were imputed using non-responder imputation.
• For continuous variables, least-squares means (95% confidence interval [CI]) were calculated for NAPSI, and treatment groups were compared using analysis of covariance, with treatment, weight (≤100 kg, >100 kg), geographic region (Western EU, Eastern EU, North America) and baseline NAPSI score as factors.
  • Missing data were imputed using modified baseline observation carried forward.
• No multiplicity correction was done for the nail endpoints as per study protocol.

Results

Baseline Patient Characteristics

• At baseline, 105 patients randomized to STELARA group and 84 patients randomized to ixekizumab group had nail PsO.¹
  • Of these patients, 63/105 (60.0%) patients in the STELARA group and 54/84 (64.3%) in the ixekizumab group had significant nail PsO, defined as fingernail NAPSI ≥16 and ≥4 fingernails involved.
• Mean baseline NAPSI (±standard deviation [SD]) scores were 24.8 (±20.0) and 28.3 (±19.9) in the STELARA and ixekizumab groups, respectively.

Efficacy

• There were significantly more patients with baseline nail psoriasis who achieved complete resolution (NAPSI 0) with ixekizumab than with STELARA by week 16 (31.0% vs. 16.2%, respectively; P=0.02) and through week 52 (61.9% vs. 28.6%, respectively; P<0.001).¹
• There were significantly more patients with significant baseline nail psoriasis that achieved complete resolution with ixekizumab than with STELARA by week 20 (25.9% vs. 9.5%, respectively; P=0.03) and through week 52 (57.4% vs. 17.5%, respectively; P<0.001).
• By week 8, average improvement in NAPSI score was significantly greater in ixekizumab-treated patients than in STELARA-treated patients (ixekizumab: -6.6; 95% CI, -8.9 to -4.3 vs. STELARA: -2.1; 95% CI, -4.1 to -0.1; P=0.002).
• Though week 52, average improvement in NAPSI score remained significantly greater in ixekizumab group compared with STELARA group (ixekizumab: -22.4; 95% CI, -24.8 to -20.0 vs. STELARA: -15.6; 95% CI, -17.8 to -13.4; P<0.001).
• At week 52, PASI 100 (complete skin clearance) response rates when nail PsO was present was 27.6% in STELARA group and 53.6% in ixekizumab group. When nail PsO was absent, PASI 100 at week 52 was 49.2% in STELARA group and 50.0% in ixekizumab group.
• Total NAPSI and PASI scores improved together by week 24, with concurrent improvement continued through week 52 in both treatment groups.
• At week 52, 21.5% of STELARA-treated patients and 7.8% of ixekizumab-treated patients presented with significant nail psoriasis (P=0.02).

PHOENIX 1

Rich et al (2014)² assessed improvement in fingernail PsO in the PHOENIX 1 trial (A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial Evaluating the Efficacy and Safety of CNTO 1275 in the Treatment of Subjects with Moderate to Severe Plaque-type Psoriasis Followed by Long-term Extension).

Study Design/Methods

• Adult patients with a diagnosis of plaque PsO for ≥6 months who were candidates for phototherapy or systemic therapy, had a baseline PASI score ≥12, and ≥10% of their BSA involved were eligible for enrollment.
• Eligible patients were randomized in equal proportions to 1 of 3 treatment groups:
  • STELARA 45 mg administered subcutaneously (SC) at weeks 0 and 4, and every 12 weeks.
  • STELARA 90 mg SC at weeks 0 and 4, and every 12 weeks.
  • Placebo at weeks 0 and 4, with half randomized to crossover to 45 mg and half to 90 mg at week 12.
• Patients who were initially randomized to STELARA at baseline and who achieved longterm response (ie, achieved ≥75% improvement from baseline in PASI score at weeks 28 and 40) were rerandomized at week 40 to either continue treatment with STELARA or to placebo (initial responders).
• Patients randomized to placebo at week 40 were retreated with STELARA at their original regimen when they lost ≥50% of their PASI improvement (randomized withdrawal).
• If a 75% reduction in the PASI score (PASI 75 response) was not achieved at weeks 28 or 40, the patients were not rerandomized and their treatment was discontinued or modified.
• The primary endpoint was the proportion of patients achieving a PASI 75 response at week 12.
• NAPSI was assessed at baseline and patients with fingernail involvement were included in this analysis (overall nail PsO population). The fingernail with the most PsO involvement was used as the target nail for Efficacy assessment.
• Improvement in nail PsO was evaluated by NAPSI, the Nail Physician’s Global Assessment (Nail PGA; range from 1-5 [1, none; 2, mild; 3, moderate; 4, severe; 5, very severe]), and the number of fingernails affected at weeks 12 and 24 in the overall nail PsO population. The initial responders were also evaluated at week 52.

Results

Baseline Patient Characteristics

• Of 766 patients randomized to receive STELARA 45 mg (n=255), STELARA 90 mg (n=256), or placebo (n=255), 545 (71.1%) had nail PsO at baseline.
• The mean NAPSI score was 4.4, and 50% of patients were categorized as having mild, 40% as moderate, and 10% as severe or very severe nail involvement based on Nail PGA scores.
• The mean number of nails involved was 6.6 in all treatment groups.

Efficacy

• NAPSI scores:
  • At week 12, percent improvement in NAPSI score was 26.7% in patients treated with STELARA 45 mg and 24.9% in those treated with STELARA 90 mg, compared to 11.8% in placebo-treated patients (P≤0.001 for 45 mg and 90 mg vs placebo, respectively).
  • Improvement continued through week 24 in the STELARA 45-mg (46.5%) and 90mg (48.7%) groups. In patients initially randomized to placebo who crossed over to STELARA at week 12, improvements in NAPSI scores were comparable to week 12 improvements in patients initially receiving STELARA 45 mg (29.1%).
• Nail PGA scores:
  • No significant improvements in Nail PGA scores were apparent in the overall nail PsO population at week 12.
  • At week 24, in patients with a baseline Nail PGA score of 2 (mild), 21% and 12% of patients in the STELARA 45-mg and 90-mg groups improved to a score of 1 (no PsO), respectively.
  • In patients with a baseline score of 3 (moderate), 77% and 75% of patients in the STELARA 45-mg and 90-mg groups improved to a score of 1 or 2 (no PsO or mild), respectively.
  • Of the patients with severe or very severe nail PsO involvement, 72% of patients in the STELARA 45-mg group and 95% of patients in the STELARA 90-mg group improved to a score of ≤3 (moderate, mild, or none).
• Number of nails with PsO:
  • At week 12 in the overall nail PsO population, full clearance (no nail involvement) was achieved by 9.3%, 5.4%, and 4.0% of the patients receiving STELARA 45 mg, 90 mg, and placebo, respectively.
  • At week 24, the percentages improved to 15.2% in the STELARA 45-mg group, and to 8.8% in the 90-mg group. Of patients who crossed-over to receive STELARA 45 mg and 90 mg at week 12, 12.5% and 10.4% achieved full nail clearance, respectively.
  • At week 52, 32.4% of patients in the maintenance group achieved full nail clearance vs 15.7% in the randomized withdrawal group.

Phase 2/3 Study

Igarashi et al (2012)³ reported results from a double-blind, placebo-controlled study assessing the safety and efficacy of STELARA in Japanese patients with moderate to severe plaque PsO.

Study Design/Methods

• Adult patients (≥20 years of age) with moderate to severe plaque PsO for at least 6 months, ≥10% BSA involvement, a baseline PASI score of ≥12, and who were candidates for phototherapy or systemic PsO treatment were included.
• Patients were randomized to receive: STELARA 45 mg, STELARA 90 mg, or placebo at weeks 0, 4, and every 12 weeks thereafter. All placebo patients crossed over in a randomized fashion to receive STELARA 45 mg or 90 mg at week 12.
• Study design:
  • Placebo-controlled period: weeks 0-12
  • Active treatment period: weeks 12-64
  • Follow-up period: weeks 64-72
• The primary endpoint was the proportion of patients achieving a PASI 75 response at week 12. Improvement in NAPSI score from baseline to weeks 12-64 in patients with baseline nail PsO involvement was among the secondary endpoints.

Results

Efficacy

• The study included 158 patients (median age, 46 years; 80.3% male) randomized to STELARA 45 mg (n=64), STELARA 90 mg (n=62), and placebo (n=32).
• Of these, 64.6% (102/158) had nail PsO at baseline (placebo, n=18; STELARA 45 mg, n=44; STELARA 90 mg, n=40) with a mean NAPSI score of 4.0±2.0.
• At week 12, the mean improvement (±standard deviation [SD]) in NAPSI score was 7.7 (±95.1) and 10.0 (±66.1) in the STELARA 45-mg and STELARA 90-mg groups, respectively, vs -2.9 (±27.8) in the placebo group (P-values nonsignificant vs placebo).
• At week 64, the mean improvement (±SD) in NAPSI scores was 56.6% (±43.2) and 67.8% (±37.5) in the STELARA 45-mg and STELARA 90-mg groups, respectively.

Open-Label Studies

Patsatsi et al (2013)⁴ evaluated the use of STELARA in 27 patients with moderate to severe plaque PsO with nail involvement in an open-label, uncontrolled study.

Study Design/Methods

• Patients were eligible if they had moderate to severe plaque PsO with nail involvement, a PASI score >10, and were over the age of 18. A 16-week washout period from other PsO treatments was required.
• All patients received STELARA 45 mg or 90 mg (for patients weighing >100 kg) at weeks 0, 4, and every 12 weeks thereafter. NAPSI (0-160 scale representing the total nail number) was assessed at baseline and weeks 16, 28, and 40.

Results

• Of the 27 patients, 12 were male and no patients weighed >100 kg. The mean age was 48.7±14.9 years with a median duration of PsO diagnosis of 7 years (range, 1-44 years).
• The median NAPSI score decreased from 73.0 (range, 12.0-151.0) at baseline to 37.0 (range, 7.0-92.0) at week 16, 9.0 (range, 0.0-32.0) at week 28, and to 0.0 (range, 0.012.0) at week 40 (P<0.0001 for all timepoints vs baseline).
• Compared to baseline, the median percent improvement in NAPSI score was 42.5% (range, 21.9%-64.9%) at week 16, 86.3% (range, 75.0%-100.0%) at week 28, and 100.0% (range, 91.0%-100.0%) at week 40 (P<0.0001 for all timepoints vs baseline).
• No adverse events were observed or reported.

Rigopoulos et al (2011)⁵ evaluated the efficacy of STELARA in 27 patients with plaque PsO and nail involvement in an open-label, prospective study.

Study Design/Methods

• Patients were included if they had failed previous systemic PsO treatments and were scheduled to receive treatment with STELARA for active plaque PsO with nail involvement. Patients underwent a 12-week washout period from other systemic and topical medications for PsO.
• STELARA was administered at 45 mg and 90 mg (patients >100 kg) at weeks 0, 4, 16, and every 12 weeks thereafter.
• NAPSI was assessed at baseline and weeks 4, 16, 28, and 40.

Results

• Twenty-seven patients were included in this analysis (10 male, age range 32-60 years) with a mean (±SD) baseline NAPSI score of 19.59 (±7.924).
• At week 4, the mean NAPSI score was reduced to 16.96 (P<0.001 compared to baseline). Mean scores at weeks 16, 28, and 40 were also significantly reduced compared to baseline (P<0.001 for all comparisons).
• No adverse events were reported.

Retrospective Study

Bardazzi et al (2017)⁶ conducted a retrospective study evaluating the time to achieve a PASI 75 in patients with and without nail PsO treated with biologic therapy and the efficacy of biologic therapy to improve nail PsO.

Study Design/Methods

• One hundred twenty-seven patients (88 men and 39 women) with moderate to severe PsO were included.
• Patients were ≥18 years of age and were treated with topical therapy (calcipotriol and betamethasone gel) along with 1 of 4 biologic therapies (adalimumab [44.09%], etanercept [18.11%], infliximab [13.39%] or STELARA [24.41%]) without switching biologic treatment for 24 weeks.
• PASI and NAPSI were assessed every 4 weeks.

Results

• Baseline characteristics were similar between patients with and without nail PsO.
• A greater percentage of males (82.93%) were affected by nail PsO.
• Patients had previously been treated with at least 2 traditional agents (methotrexate, cyclosporine, acitretin or PUVA therapy).
• PASI 75 at week 24 was achieved by a smaller proportion of patients with nail PsO than those without nail PsO involvement (80.23% vs 65.85%, respectively; HR, 0.60; 95% CI, 0.37-0.97; P<0.05).
• All 4 biologic therapies were effective in reducing NAPSI scores with improvement seen starting after 8 weeks of treatment.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 08 April 2024.