Introduction

Psoriasis is a chronic systemic inflammatory disease associated with multiple comorbidities, requiring sustained and effective long‑term therapy. Secukinumab is an anti‑IL‑17A monoclonal antibody that has shown strong efficacy & safety in randomized clinical trials for moderate‑to‑severe psoriasis. However, long‑term real‑world evidence beyond 3–4 years is limited. 

Aim

To evaluate the long‑term effectiveness & safety of secukinumab in patients with moderate‑to‑severe plaque psoriasis in real‑world clinical practice, with follow‑up of up to 7 years. 

Patient Profile

The study included adults with moderate‑to‑severe plaque psoriasis.

Methods

• Multicenter, retrospective, real‑world study
• The study enrolled 769 adult patients (> 18 yrs) with moderate-to-severe plaque psoriasis who had received secukinumab for at least 4 years across 15 Italian dermatology units.

Study Endpoints

• PASI 90  (reduction of at least 90% in PASI score from baseline)
• PASI 100 (complete clearance)
• Absolute PASI ≤ 2 

• Subgroup Analyses: Subgroup analyses were performed to compare treatment effectiveness according to the involvement of at least one difficult-to-treat area, the presence of at least one cardiometabolic comorbidities (CMD; defined as the presence of at least one of the following: arterial hypertension, hypercholesterolemia, type-2 diabetes mellitus [T2DM], obesity, or a history of major adverse cardiovascular events [MACE]), concomitant PsA,previous exposure to other biological agents, involvement of difficult-to-treat areas (scalp/face, nails, genitalia, and palms/soles) and thepresence of concomitant PsA.

• Safety Endpoints
  1. Incidence of adverse events (AEs)
  2. Serious AEs and treatment discontinuation

Results

All 769 patients completed 4 years of treatment; 669, 231, and 101 patients were followed for 5, 6, and 7 years, respectively.

Table 1: Baseline characteristics

Characteristic	Value
Age (years), mean ± SD	56.6 ± 13.7
Gender (Male)	494 (64.2%)
Gender (Female)	275 (35.8%)
BMI (kg/m²), mean ± SD	26.6 ± 4.4
Disease duration (years), mean ± SD	20.2 ± 12.7
Baseline PASI, mean ± SD	15.3 ± 5.9
Bio‑naïve	447 (58.1%)
Psoriatic arthritis (PsA)	249 (32.4%)
Difficult‑to‑treat areas (≥1)	461 (59.9%)
• Face/scalp	272 (35.4%)
• Nails	201 (26.1%)
• Genital area	126 (16.4%)
• Palmoplantar	115 (15.0%)
≥1 cardiometabolic comorbidity (CMD)	396 (51.5%)
• Arterial hypertension	260 (33.8%)
• Type 2 diabetes mellitus	109 (14.2%)
• Obesity	114 (14.8%)
• Hypercholesterolemia	83 (10.8%)
• Major adverse cardiovascular events	57 (7.4%)
• MAFLD	9 (1.2%)
Chronic infections	26 (3.4%)
• Hepatitis B (HBV)	4 (0.5%)
• Hepatitis C (HCV)	7 (0.9%)
• HIV	1 (0.1%)
• Latent tuberculosis (LTBI)	15 (2.0%)
Prior neoplasm	27 (3.5%)
Thyroid disease	48 (6.2%)
Anxiety/depressive disorders	13 (1.7%)

 

Effectiveness

• At Week 16
  1. PASI 90 response was observed in 277 patients (36%)
  2. PASI 100 (complete clearance) in 211 patients (27.4%)
  3. Absolute PASI ≤2 achieved by 356 patients (46.3%)
• At Week 32, improvement was noted with: 
  1. PASI 90 was achieved in 420 patients (54.6%)
  2. PASI 100 was achieved in 318 patients (41.4%)
  3. PASI ≤2 was achieved in 538 patients (70.0%)
• At Year 1 sustained responses were seen 
  1. PASI 90 response rate was 546 patients (71.0%)
  2. PASI 100 response rate was 414 patients (53.8%)
  3. PASI ≤2 response rate was 621 patients (80.8%)
• At year 2response rates further increased: 
  1. PASI 90 was achieved in 72.4%
  2. PASI 100 was achieved in 53.6%
  3. PASI ≤2 was achieved in 82.6%
• At year 3continued improvement was observed
  1. PASI 90 response rate was 78.2%
  2. PASI 100 response rate was 57.6%
  3. PASI ≤2 response rate was 87%
• At year 4, higher levels of response were achieved 
  1. PASI 90 response rate was 84.1%
  2. PASI 100 response rate was 67.1%
  3. PASI ≤2 response rate was 91.4%
• At year 5(n = 669 patients)responses were maintained or improved: 
  1. PASI 90 response rate was 582 patients (87%)
  2. PASI 100 response rate was 484 patients (72.3%)
  3. PASI ≤2 response rate was 617 patients (92.2%)
• At year 6(n = 231 patients) high response rates sustained were reported 
  1. PASI 90 response rate was 90%
  2. PASI 100 response rate was 75.3%
  3. PASI ≤2 response rate was 94.4%
• At year 7(n = 101 patients) long-term outcomes remained stable: 
  1. PASI 90 response rate was 89.1%
  2. PASI 100 response rate was 80.2%
  3. PASI ≤2 response rate was 95.0%
• In patients who continued secukinumab therapy for at least 4 years, clinical responses were not only maintained but gradually improved over time. 

Figure 1:Secukinumab effectiveness throughout the entire study period

              

Subgroup Analyses at Long‑Term Follow‑Up (Yrs 4–7)

• Secukinumab effectiveness was consistent across most patient subgroups. 
• Only PsA subgroup showed superior long‑term response (especially complete clearance)

PsA (PsA vs no PsA)

• Patients with PsA showed significantly better outcomes at later time points (years 5 and 6)
• Higher PASI 100 at year 5 (77.9%  vs 69.8%, p<0.05)
• Higher PASI 90 and PASI 100 at year 6 (p<0.05)

Table 2 : Subgroup Analyses outcomes: PsA ( PsA vs no PsA)

Year	Outcome	PsA (%)	No PsA (%)	p‑value
4	PASI 90	83.1	84.6	0.598
	PASI 100	67.1	67.1	0.990
	PASI ≤2	92.4	91.0	0.514
5	PASI 90	89.4	85.9	0.210
	PASI 100	77.9	69.8	0.031
	PASI ≤2	94.2	91.3	0.194
6	PASI 90	96.8	87.5	0.035
	PASI 100	85.7	71.4	0.025
	PASI ≤2	98.4	92.9	0.121
7	PASI 90	91.7	88.3	1.000
	PASI 100	83.3	79.2	0.776
	PASI ≤2	100	93.5	0.335

Cardiometabolic Comorbidities (CMD): CMD vs no CMD

• No significant impact on treatment response at any time point was reported
• PASI 90, PASI 100, and PASI ≤2 rates were similar between groups

Table 3 : Subgroup analysis outcomes :CMD (CMD vs no CMD)

Year	Outcome	CMD (%)	No CMD (%)	p‑value
4	PASI 90	83.6	84.7	0.667
	PASI 100	64.9	69.4	0.181
	PASI ≤2	90.4	92.5	0.301
5	PASI 90	88.7	85.4	0.204
	PASI 100	74.3	70.5	0.266
	PASI ≤2	92.4	92.1	0.904
6	PASI 90	89.4	90.7	0.742
	PASI 100	77.0	73.7	0.565
	PASI ≤2	93.8	94.9	0.714
7	PASI 90	90.7	87.9	0.755
	PASI 100	83.7	77.6	0.444
	PASI ≤2	95.3	94.8	1.000

 

Difficult‑to‑treat areas (Difficult areas vs none)

• Presence of difficult areas (scalp, nails, palms, genital) did not affect effectiveness.
• Comparable response rates were observed across all years

Table 4 : Response Rates Across All Years

Year	Outcome	Difficult Areas (%)	None (%)	p‑value
4	PASI 90	84.2	84.1	0.978
	PASI 100	66.2	68.5	0.497
	PASI ≤2	91.8	90.9	0.681
5	PASI 90	87.2	86.7	0.859
	PASI 100	71.6	73.4	0.605
	PASI ≤2	93.2	90.8	0.247
6	PASI 90	91.6	88.0	0.365
	PASI 100	75.6	75.0	0.920
	PASI ≤2	95.4	93.0	0.429
7	PASI 90	89.8	88.1	1.000
	PASI 100	84.7	73.8	0.174
	PASI ≤2	96.6	92.9	0.647

 

Safety Results 

• The safety profile of secukinumab in this cohort remained consistently favorable throughout the entire follow‑up period. 
  • Non‑serious adverse events were reported in 7% of patients (Most common: upper respiratory tract infections)
  • Serious events were seen in 0.7%, including 3 malignancies , 1 pulmonary embolism, 1 eosinophilic pneumonia.
  • Regarding chronic infections, no reactivation of LTBI, viral hepatitis, or HIV was observed throughout the study period.

Table 5. Safety profile of secukinumab during follow-up (N = 769)

Adverse Event	n (%)
Non-serious adverse events	54 (7.0%)
• Upper respiratory tract infections (URTI)	36 (4.7%)
• Candida infections	10 (1.3%)
• Headache	3 (0.4%)
• Eczematous reaction	2 (0.3%)
• Asthenia	2 (0.3%)
• Arthralgia	1 (0.1%)
Serious adverse events	5 (0.7%)
• De novo malignancies	3 (0.4%)
– Breast cancer	1
– Endometrial cancer	1
– Thyroid carcinoma	1
• Massive pulmonary embolism	1 (0.1%)
• Eosinophilic pneumonia	1 (0.1%)

 

Conclusion

• Secukinumab showed sustained long‑term effectiveness and a favorable safety profile for up to 7 years in real‑world settings, with response rates comparable to those reported for other IL‑17 inhibitors, particularly ixekizumab, in terms of PASI 90 and PASI 100.

• Clinical responses , PASI 90, PASI 100, and PASI < 2 response rates improve progressively with continued therapy, regardless of presence of CMD or involvement of difficult-to-treat areas. 
• Patients with psoriatic arthritis may achieve superior skin clearance rates at years 5 and 6, highlighting a potential added benefit in this subgroup. 

Reference

Dermatol Ther (Heidelb) (2026). https://doi.org/10.1007/s13555-026-01797-9