Real-World Effectiveness and Safety of Ixekizumab in Moderate-to-Severe Plaque Psoriasis in the Indian Population: A Pilot Study

Abstract

Background:

India has a significant burden of psoriasis, with an incidence reported between 0.44% and 2.2% among total dermatology patients and a reported prevalence of 4.78% over 5 years. Psoriasis is now recognized as a multisystem disease, and targeted therapies are needed to reduce morbidity. The need for newer biologics exists not only for better disease control but also to treat patients who manifest primary or secondary failure to a previous biologic. Ixekizumab is a newer IL-17 inhibitor that has recently been approved by the Drug Controller General of India for use in patients with psoriasis vulgaris in India.

Aims and Objectives:

To evaluate the effectiveness and safety of ixekizumab in the treatment of patients with plaque psoriasis of Indian origin.

Patients and Methods:

The study was a prospective, single-center, single-arm interventional study approved prospectively by Clinical Trial Registry-India with reg. no. CTRI/2025/02/081205. The induction phase of ixekizumab was used to treat 40 patients with moderate-to-severe plaque psoriasis. The psoriasis area severity index (PASI), body surface area (BSA), and dermatology life quality index (DLQI) were measured at 2, 4, and 12 weeks of therapy. Median values of absolute PASI and BSA were assessed statistically using the Friedman test and Wilcoxon-signed rank test. PASI 75/90/100 responses were measured at 2, 4, and 12 weeks and analyzed using Cochran’s Q test and McNemar test. Safety and adverse events, if any, were documented.

Results:

The median absolute PASI, BSA, and DLQI showed progressive improvement during the study period and these values when compared between baseline and 12 weeks were statistically significant. PASI 75/90/100 at the end of 12 weeks was 100%, 75%, and 20%, respectively. All eleven patients who had primary or secondary failure to a previous biologic showed a comparable response to that achieved by biologic naïve patients. No major adverse events were noted.

Limitations:

Considering that it is a pilot study which concluded in the induction phase of the treatment, long-term treatment outcomes and adverse events cannot be commented upon.

Conclusion:

Ixekizumab achieved high PASI targets during the induction phase. The treatment improved the DLQI significantly. It has an excellent safety profile in the Indian population. Its effectiveness in patients with previous biologic failure is comparable to that in biologic naïve patients.

Introduction

India has a significant burden of psoriasis, with reported incidence between 0.44% and 2.2% among total skin patients and prevalence being 4.78% over 5 years.[1]

In the last two decades, biologic therapies have revolutionized the treatment of most dermatologic diseases, including plaque psoriasis. With increasing demand for better treatment outcomes and improved quality of life, these targeted therapies are becoming more popular. Approved biologics for psoriasis include tumor necrosis factor inhibitors (TNFi), interleukin-17A inhibitors (IL-17i), interleukin-12/23 inhibitors (IL-12/23i), and interleukin-23 inhibitors (IL-23i).[2,3] There is a continuing need for newer molecules that can achieve faster and sustained outcomes, with minimal to no adverse events compared to the currently available options. These molecules should also be able to treat patients who have had primary or secondary treatment failures to previous biologics and now require switching. Ixekizumab is one such newer molecule.

Ixekizumab is an IgG4 monoclonal antibody that selectively targets and binds IL-17A, with very high affinity.[4] The Food and Drug Administration and European Medicines Agency approved the molecule in 2016 for treating patients with moderate-to-severe plaque psoriasis.[5] Since then, various studies have highlighted the molecule’s faster onset of action and good safety profile, including the UNCOVER- 3 study by Blauvelt et al.[6] Most of the available trials and studies have been funded by the manufacturing or marketing company.[7] By observing outcomes in diverse populations and environments, real-world studies offer valuable information on effectiveness, safety, and practical implications.

Certain differences in the efficacy of biologics exists in different ethnic groups. Biologic agents such as secukinumab, brodalumab and ixekizumab have been studied to have superior efficacy in non-white racial/ethnic group.[8] Studies in Chinese and White psoriasis patients with HLA-Cw*06 showed a greater, faster, and longer duration of response to ustekinumab, highlighting the role of pharmacogenetics.[9] Studies from Indian (skin of color) patients regarding the efficacy and safety of ixekizumab in treating moderate-to-severe plaque psoriasis are lacking.

We studied this molecule at our tertiary care hospital to evaluate the drug’s effectiveness and safety during treatment of psoriatic patients of Indian origin. We also assessed its response in patients who have experienced primary or secondary biologic treatment failure. This is a pioneer work restricted to the induction phase, i.e. till 12 weeks; however, the molecule continues to be studied for long-term treatment outcome at our center.

Patients and Methods

Description of the study and ethics

This was a prospective, single-center, single-arm, interventional study conducted in the dermatology department of Base Hospital Delhi Cantt, New Delhi, which is a tertiary care teaching hospital and medical college. The study was designed in September 2024, following the recent approval of ixekizumab by Drug Controller General of India for use in India (March 2023).

Drug procurement was arranged through the hospital medical stores, which provide free biologic treatment to all entitled patients. Permission from the institutional ethics committee (full committee) was obtained in October 2024 (reg. no. IEC-05/2024/04).

The study was registered with the Clinical Trial Registry-India (ICMR-NIMS), and approvals were received in February 2025 (reg. no. CTRI/2025/02/081205); following which, patients were recruited, and the study was conducted. Written informed consent in the patients’ language was obtained from all participants.

Study population

This was a pilot study, and thus a small sample size was selected. The study population included 40 patients with plaque psoriasis above the age of 18 years, with psoriasis area severity index (PASI), body surface area (BSA), and dermatology life quality index (DLQI) scores greater than 10, with or without involvement of the palms and soles, nails, or joints. These included patients who were biologic naïve as well as those who had failed a previous biologic or any other immunosuppressant. Criteria for primary failure were taken as insufficient response (patients not achieving PASI 50) at week 12, and criteria for secondary failure included loss of response (PASI > 50% of the initial value) in a patient who had previously achieved PASI 50 at week 12.[10,11]

Exclusion criteria included patients with subgroups having isolated nail psoriasis, palmoplantar psoriasis, pustular psoriasis, inverse psoriasis, and psoriatic arthritis. Patients with irritable bowel disease, active tuberculosis, pregnancy, lactating females, malignancy, active infections, and drug hypersensitivity were also excluded from the study.

Study design and outcomes, disease activity measures

The study population was evaluated for demographic profile, presence of nail, palmoplantar, or joint psoriasis, comorbidities, latent tuberculosis infection (LTBI) status, prior biologic experience, and reason for switching to ixekizumab. All patients underwent baseline laboratory tests, viral markers, and interferon gamma release assay (IGRA). Patients who were IGRA positive were further investigated to rule out active tuberculosis and were treated adequately before starting ixekizumab.

All prior medications, both oral and topical, including immunosuppressants, were discontinued at the start of treatment. All patients had high disease activity and were therefore shifted to ixekizumab from previous treatment (disease modifying anti rheumatic drug/biologic) immediately, without waiting for wash out period to prevent acute exacerbation of psoriasis. Patients were advised to take levocetirizine 5 mg on a need basis during the study, for pruritus on psoriatic lesions.

The study population was treated with subcutaneous injections of ixekizumab, supplied as a prefilled syringe containing 80 mg. A standard dose of 160 mg at week 0, followed by 80 mg every 2 weeks until week 12, was used during the induction phase. PASI, BSA, and DLQI were measured for all patients at baseline and during follow-up visits at 2, 4, and 12 weeks. A smartphone-based PASI calculator (MD + CALC by Dr. Torsten Friedriksson) was used consistently for PASI calculation at all time points. PASI results from the calculator were rechecked manually. BSA was measured clinically by the Wallace’s rule of nine assessment tool. The DLQI questionnaire was reciprocated in the patients’ language by the principal investigator (PI) and scored.

Hemogram, liver and kidney function tests were repeated at 2, 4, and 12 weeks to assess for any side effects of treatment. Patients were instructed to report any adverse events after the administration of the injection directly to the PI via telephone or during follow-up visits.

Statistical analysis

Statistical analysis was done using the statistical package for the social sciences version 21.0. Categorical variables, including age, gender, presence of nail, palmoplantar, or joint psoriasis, comorbidities, LTBI status, prior biologic experience, and reason for switching to ixekizumab, were summarized using percentages.

Continuous variables, such as means, standard deviations, and the 25^th, 50^th (median), and 75^th percentiles of PASI, BSA, and DLQI, were tabulated at baseline, 2, 4, and 12 weeks.

As response outcome was measured at four different time frames, two nonparametric tests, namely Friedman and Wilcoxon signed-rank test, were used to analyze the values of PASI, BSA, and DLQI at these time points. P value and z-score were used to indicate significance in the outcomes of PASI, BSA, and DLQI after treatment. Normality of BSA, PASI, and DLQI was checked at all intervals using Kolmogorov–Smirnov and Shapiro–Wilk tests.

PASI 75/90/100 responses were also calculated at 2, 4, and 12 weeks using a yes/no analysis and expressed as percentages. To evaluate whether response rates differed across the three time points, Cochran’s Q test was conducted. Upon finding a significant Cochran’s Q test, post hoc pairwise comparisons were performed using McNemar’s test to examine differences between each pair of time points. To control for Type I error due to multiple comparisons, a Bonferroni correction was applied, setting the significance threshold at P < 0.017 (0.05/3). All tests were two-tailed, and P values less than 0.05 were considered statistically significant unless otherwise adjusted.

Thus, both absolute PASI and PASI 75/90/100 were used to assess the response to therapy. There were no treatment dropouts, and thus no attrition rates.

Results

Patient characteristics

The mean age of the patients was 43.4 years. Of the 40 patients, 22 (55%) were male and 18 (45%) were female. In addition to plaque psoriasis, three (7.5%) patients had palmoplantar involvement, five (12.5%) had nail involvement, and two (5%) had psoriatic arthritis. Fourteen patients (35%) had a known comorbidity, the most common being metabolic syndrome; one patient was a special child with Down syndrome. Six patients (15%) had LTBI [Table 1].

Table 1.

Demographic data, clinical profile and previous treatment with biologic in study patients

Particulars	Value
Total number of patients	40
Mean age	43.4 yrs
Gender	22 males and 18 females
Associated palmoplantar involvement	3 (7.5%) patients
Associated nail involvement	5 (12.5%) patients
Associated psoriatic arthritis	2 (5%) patients
Patients with co-morbidities	14 (35%) patients
Latent tuberculosis infection	6 (15%) patients
Biologic experienced	15 (37.5);
	Secukinumab-9 (60%);
	Adalimumab-4 (26.66%);
	Etanercept-1 (6.66%);
	Infliximab-1 (6.66%)
Biologic naïve	25 (62.5%) patients
Failure of treatment with prior biologic	11 (27.5%);
	Secondary failure (8, 20%)
	Primary failure (3, 7.5%)

Prior treatment with biologic

Fifteen patients (37.5%) had prior experience with biologics [secukinumab: 9 (60%), adalimumab: 4 (26.66%), etanercept: 1 (6.66%), and infliximab: 1 (6.66%)]. Reasons for switching to ixekizumab included secondary failure (8, 53.33%), primary failure (3, 20%), adverse events to biologics (2, 13.33%), and treatment dropouts (2, 13.33%) during remission. Twenty five patients (62.5%) were biologic naïve [Table 1].

PASI, BSA, and DLQI after treatment with ixekizumab

The median absolute PASI and interquartile range (IQR) at baseline, 2, 4, and 12 weeks of treatment was 29.75 (20-38.75), 9.25 (6.5-12.45), 4.6 (3-6), and 1.8 (1-3.15), respectively. A Friedman test showed a P < 0.001, which was statistically significant. The median BSA and IQR at baseline, 2, 4, and 12 weeks were 35.5 (25.5–45), 18.5 (12–25.75), 9 (6–13.75), and 4 (1–5), respectively, and a Friedman test showed a P < 0.001, which was statistically significant. The median DLQI and IQR at baseline, 2, 4, and 12 weeks were 17.4 (14–19), 5 (4–6), 3 (2–3.75), and 1 (1–2), respectively, and a Friedman test showed a P < 0.001, which was statistically significant [Table 2]. Wilcoxon signed-rank test scores for PASI, BSA, and DLQI showed consistent negative rank and statistically significant results across all compared intervals of treatment [Table 3].

Table 2.

Median, IQR values and statistical results of PASI, BSA and DLQI using Friedman test

	Percentiles		Chi-Square test	P
	50th (Median)	IQRs (Q1-Q3)
PASI			119.707	<.001
Baseline	29.75	(20-38.75)
2 weeks	9.25	(6.50-12.450)
4 weeks	4.6	(3.0-6.0)
12 weeks	1.8	(1.00-3.15)
BSA			118.564	<.001
Baseline	35.5	(25.5-45)
2 weeks	18.5	(12-25.75)
4 weeks	9	(6-13.75)
12 weeks	4	(1-5)
DLQI			117.735	<.001
Baseline	17.5	(14-19)
2 weeks	5	(4-6)
4 weeks	3	(2-3.75)
12 weeks	1	(1-2)

BSA – body surface area, DLQI – dermatology life quality index, IQR – interquartile range, PASI – psoriasis area severity index

Table 3.

Wilcoxon signed-rank test results for comparison of median values of PASI, BSA and DLQI at different study intervals

	Comparison	Z	P
Wilcoxon signed-rank test for PASI score (n=40)	Baseline vs 2 weeks	-5.511	<0.001
	Baseline vs 4 weeks	-5.511	<0.001
	Baseline vs 12 weeks	-5.512	<0.001
	2 weeks vs 4 weeks	-5.514	<0.001
	2 weeks vs 12 weeks	-5.512	<0.001
	4 weeks vs 12 weeks	-5.453	<0.001
Wilcoxon signed-rank test for BSA score (n=40)	Baseline vs 2 weeks	-5.514	<0.001
	Baseline vs 4 weeks	-5.513	<0.001
	Baseline vs 12 weeks	-5.512	<0.001
	2 weeks vs 4 weeks	-5.515	<0.001
	2 weeks vs 12 weeks	-5.513	<0.001
	4 weeks vs 12 weeks	-5.344	<0.001
Wilcoxon signed-rank test for DLQI score (n=40)	Baseline vs 2 weeks	-5.518	<0.001
	Baseline vs 4 weeks	-5.523	<0.001
	Baseline vs 12 weeks	-5.517	<0.001
	2 weeks vs 4 weeks	-5.517	<0.001
	2 weeks vs 12 weeks	-5.538	<0.001
	4 weeks vs 12 weeks	-5.251	<0.001

BSA – body surface area, DLQI – dermatology life quality index, n – total number of patients, PASI – psoriasis area severity index

The mean values of PASI, BSA, and DLQI at baseline, 2, 4, and 12 weeks after treatment with ixekizumab are graphically represented in Figure 1.

Figure 1.

Mean values of treatment outcomes at different study intervals. BSA: Body surface area, DLQI: Dermatology life quality index, PASI: Psoriasis area severity index

PASI 75/90/100 responses at 2 weeks were achieved by 10%, 0%, and 0% patients; at 4 weeks were achieved by 82.5%, 20%, and 0% patients; and at 12 weeks were achieved by 100%, 75%, and 20% patients, respectively. The Null hypothesis showed that the distributions of PASI 75/90/100 at 2, 4, and 12 weeks were similar. Cochran’s Q test, when applied to the related samples of PASI (75/90/100) at 2, 4, and 12 weeks, showed P values of. 0.018, 0.00, 0.00, respectively, which were statistically significant. Post hoc pairwise McNemar tests with Bonferroni correction revealed significant increases in response rates between study intervals for PASI 75/90/100 [Table 4].

Table 4.

Cochran’s Q and McNemar test results for PASI responses at various intervals

PASI response	Week 2	Week 4	Week 12	Cochran’s Q (df)	P	Pairwise Comparisons (Bonferroni corrected)
PASI 75	10% (4/40)	82.5% (33/40)	100% (40/40)	60.72 (2)	<0.001	W2 vs W4: <0.001 (Yes)W4 vs W12: 0.002 (Yes)W2 vs W12: <0.001 (Yes)
PASI 90	0% (0/40)	20% (8/40)	75% (30/40)	48.27 (2)	<0.001	W2 vs W4: 0.008 (Yes)W4 vs W12: <0.001 (Yes)W2 vs W12: <0.001 (Yes)
PASI 100	0% (0/40)	0% (0/40)	20% (8/40)	80.00 (2)	<0.001	W2 vs W4: – (NA)W4 vs W12: <0.001 (Yes)W2 vs W12: <0.001 (Yes)

BSA-body surface area, DLQI-disease life quality index, PASI-psoriasis area severity index, W2=Week 2, W4=Week 4, W12=Week 12. Note: “NA” indicates pairwise comparison not applicable due to identical response rates, Bonferroni correction applied for three pairwise comparisons (α=0.017)

Patients with secukinumab failure had median absolute PASI and IQR values of 26.5 (15–45), 10.95 (5.7–13), 4.5 (3–7.5), and 2.5 (0–3.5) at baseline and at 2, 4, and 12 weeks, respectively. Among these patients, PASI 75/90/100 responses at 2 weeks were achieved by 0%, 0%, and 0% patients; at 4 weeks by 66.67%, 16.66%, and 0% patients; and at 12 weeks by 100%, 50%, and 33.34% patients, respectively.

Patients with TNFi (adalimumab and etanercept) failure had median absolute PASI and IQR values of 38 (21.1–42.5), 12 (6–20), 5 (2.8–11.1), and 2 (0.5–5) at baseline and at 2, 4, and 12 weeks, respectively. Among adalimumab failures, PASI 75/90/100 responses at 2 weeks were achieved by 0%, 0%, and 0% patients; at 4 weeks by 80%, 20%, and 0% of patients; and at 12 weeks by 100%, 80%, and 20% of patients, respectively.

At follow-up visits, no significant clinical improvement was observed in either nail or palmoplantar lesions; however, these were not assessed separately by a different scoring system, which did not impact the outcome of our study. All patients with psoriatic arthritis remained symptom-free and showed no disease activity, but improvement was not graded.

Safety and adverse events

Treatment with ixekizumab demonstrated an excellent safety profile, with no major side effects of interest noted over 12 weeks. However, three (7.5%) patients experienced mild-to-moderate itching on psoriatic lesions a few hours after the first dose of ixekizumab (160 mg). This was managed with antihistamines for 5 days, resulting in complete resolution of symptoms and no recurrences with subsequent doses. Laboratory profiles of patients monitored during treatment did not show any worsening. Overall, there were no patient dropouts due to adverse events.

Discussion

With recent advances in targeted therapies, patients with psoriasis desire faster and more sustained responses. In our effort to provide dramatic treatment outcomes, our experience with ixekizumab has been extremely positive and encouraging. All 40 patients in our study showed improvement in PASI and BSA at 2, 4, and 12-week follow-up visits.

Absolute PASI and BSA values were extremely relevant in this study for monitoring response. The mean and median absolute values at the end of 12 weeks were less than 5 for PASI, BSA, and DLQI, and the response was statistically significant (P < 0.001). Similar results were reported by Seidl et al.,[12] who found that 72.5% of patients achieved an absolute PASI ≤5 (55.0% ≤3; 42.5% ≤2) at the end of 12 weeks. Mrowietz et al., also reported that PASI <1, <2, <3, and <5 were achieved by 71.3%, 80.1%, 85.6%, and 88.1% of patients, respectively.[13]

Four (10%) patients achieved PASI 75 at the end of 2 weeks, demonstrating a rapid onset of treatment effects, as also highlighted by Blauvelt et al.,[14] where at week 2, patients on ixekizumab had a 16-fold greater relative PASI improvement compared to guselkumab. However, our PASI 75 response at 2 weeks was lower than in the referenced study, where 23% (119/520) of patients achieved PASI 75 at 2 weeks. At 4 weeks, PASI 90 was achieved by eight (20%) patients. Similar results were reported by Blauvelt et al.,[14] where a PASI 90 response was achieved by 21% (109/520) of patients at 4 weeks with ixekizumab. None of our patients achieved PASI 100 at 4 weeks. PASI 75/90/100 responses at the end of the induction phase (12 weeks) were 100%, 80%, and 20%, respectively, which were similar to the responses reported by Demirel Öğüt et al.[15] (92.4%, 86.1%, and 26.6%) at week 16.

The mean and the median values at 12 weeks of treatment were less than five for both biologic naïve and biologic experienced patients [Table 5]. This finding highlights that all 11 patients who had primary or secondary failure to a previous biologic (TNFi or IL17i) showed a comparable response to ixekizumab, similar to that achieved by biologic naïve patients. Lebwohl et al.[3] concluded in their study that switching biologic classes to ixekizumab led to improvements in BSA, DLQI, skin itch, and pain. Our patients also had significant improvement in itch and an overall improvement in DLQI.

Table 5.

Comparing response of PASI in biologic naive patients v/s biologic failure patients at the end of 12 weeks of ixekizumab treatment

Study population (n=36)	Median and IQR (Q1-Q3) PASI values at baseline	Median and IQR (Q1-Q3) PASI values at 12 weeks
Biologic naïve patients (n=25)	28 (20-36)	1.5 (1-3)
Secukinumab failure patients (n=6)	26.5 (15-45)	2.5 (0-3.5)
TNFi failure patients (n=5)	34 (29.5-48.5)	2 (0.5-5)

IQR – interquartile range, n- total number of patients, PASI – psoriasis area severity index, TNFi – tumor necrotic factor inhibitor. Note: n=36, since four patients were not comparable for baseline results (did not have a biologic failure); two of them had an adverse event to a previous biologic and the other two were treatment drop-out to a previous biologic.

Regarding side effects, Blauvelt et al. reported that a small subset of patients experienced upper respiratory tract infections and injection site reactions.[14] In our study, a few patients experienced mild-to-moderate itching within 24 hours after the first 160 mg dose. No other side effects were observed.

Limitation

The study had a small sample size and covered only the induction phase of treatment, resulting in a short follow-up period. Thus, this study lacks the promulgation of long-term treatment outcomes. Commenting on long-term adverse events of ixekizumab is also not possible based on results of this study. Difficult-to-treat sites and high-impact sites, such as the scalp, palms and soles, genitals, and face, were not separately studied. Our study did not include a treatment cost analysis or a comparison with the costs of other available biologics and small molecules.

Conclusion

Ixekizumab is a newer biologic option for the treatment of plaque psoriasis. The study offers significant evidence regarding faster and sustained PASI and BSA response with minimal to no side effects in the Indian population. Ixekizumab offers an equivalent response in biologic naïve patients and in those who had primary or secondary failure to either secukinumab or TNFi inhibitors. Concomitant use of methotrexate is not necessitated, as most patients achieved PASI 90 and both median and mean absolute PASI of <5 at the end of 12 weeks of treatment. This pilot study gives us confidence to use the molecule for a larger population and longer duration.

Authors’ contributions

We confirm that all authors have read and approved the manuscript for submission. All authors meet authorship criteria, and the manuscript represents honest work.

Data availability statement

The datasets generated and/or analysed during the current study are not publicly available as they include patient details, but are available from the corresponding author on reasonble request.

Conflicts of interest

There are no conflicts of interest.

Use of artificial intelligence (AI)

Smartphone-based PASI calculator (MD + CALC by Dr. Torsten Friedriksson) was used consistently for PASI calculation at all time points. PASI results from the calculator were rechecked manually by the authors.

Funding Statement

Nil.