Abstract
Psoriasis is a chronic, debilitating disease of inflammatory dermatoses. IL-17 plays a pivotal role in the pathogenesis of psoriasis. It acts as a driving force in psoriasis and has a significant role in keratinocyte proliferation, plaque progression, neutrophil recruitment, forming an amplification loop, and formation of tissue-resident memory T helper cells causing relapse. Ixekizumab is a humanized IgG4 monoclonal anti-IL-17 antibody approved for psoriasis in 2016. We are reporting a series of 22 patients presented with moderate to severe psoriasis treated with ixekizumab. 31.8% of patients had pre-existing comorbidities like Hypertension, diabetes, or hypertriglyceridemia. After 14 weeks of treatment, the Mean ± SD PASI improved from 30.82 ± 7.06 to 2.82 ± 3.12. At the end of treatment (14th week), PASI75, PASI 90, and PASI 100 were achieved by 95.45%, 68.18%, and 27.27% of patients, respectively. Friedman’s ANOVA shows a significant decrease (P < 0.05) in PASI, BSA, and sPGA scores starting from the 1st follow-up (2 weeks) onwards. Paired t-test shows a significant decrease in PAsI, BSA, and sPGA reduction, P < 0.0001 between baseline and 7th follow-up visit (14 weeks). No significant side effects were noted in this period. The present study illustrates the experience with ixekizumab in real-world clinical practice, confirming its effectiveness and safety in the management of plaque psoriasis patients.
KEY WORDS: Biologics, IL 17 blocker, Ixekizumab, psoriasis, real-world evidence
Introduction
IL-17 plays a pivotal role in the pathogenesis of psoriasis. It has a major role in keratinocyte proliferation and angiogenesis. It helps in neutrophil recruitment by induction of neutrophil-specific chemokines (e.g. CXCL1, -3, -8, IL8, CCL20, and CCL2).[1] Additionally, it facilitates the release of TNF α from DCs and macrophages. It promotes Psoriatic arthritis by upregulation of IL6, IL8, and MMP in fibroblast-like synovial (FLS) cells. It stimulates the autoantigen LL37 production and upregulates βdefensin, Cathlecidin production, which initiates the pathogenic pathway of psoriasis.[2] That’s why the introduction of IL-17 blockers in the management of psoriasis was a seminal event in the history of psoriasis treatment. IL-17 is also involved in the formation and maintenance of tissue-resident memory T cells in psoriatic skin. These cells can persist in the skin and contribute to the recurrence of psoriatic lesions, leading to relapses.[3] Biological therapy has become popular for the treatment of psoriasis for the last two decades. The first biological agent approved by the US Food and Drug Administration (USFDA) for the treatment of moderatetosevere psoriasis in 2003 is Alefacept, though it was withdrawn from the market in 2011.[4] Among the IL17 blockers, secukinumab was approved in 2015 for psoriasis patients.[5] After that Ixekizumab was approved in 2016 and brodalumab in the year 2017.[6] Ixekizumab is a humanized IgG4 monoclonal anti-IL-17 antibody, which binds to IL-17A significantly strongly than secukinumab.[7] Ixekizumab has been proven to be efficacious in managing chronic plaque psoriasis, Psoriatic arthritis, scalp, palmoplantar, nail, erythrodermic, inverse, and pustular psoriasis in different studies.[7,8,9,10,11,12] Recently, it has been launched in India on 26th November, 2022. However, there is no data available on the Indian population. Identifying the research gap, we aimed to evaluate the safety and efficacy of Ixekizumab in psoriasis patients of the Indian sub-continent.
Case-Description
We have studied 22 patients of moderate to severe chronic plaque psoriasis who were treated with Ixekizumab. The patients were included between April 2023 to August 2024 and followed up till February 2025. Patients aged between 20–60 years presented with moderate to severe chronic plaque psoriasis PASI score of 10 or more, or a BSA of >10%, and recalcitrant to treatment with at least two systemic agents, like methotrexate or Cyclosporin or recalcitrant to other biologics for at least 6 months. The sequence of injections, visits and dosing protocol is shown in Table 1. Safety was assessed through monitoring of adverse events (AEs), laboratory data, immunogenicity, electrocardiograms, and vital signs collected and reported by study investigators at regular intervals during patient visits.
Table 1.
Sequence of injections, visits and effective measures undertaken
| Screening visit | Baseline visit | 1st Follow-up at week 2 | 2nd Follow-up at week 4 | Self injection | 3rd Follow-up | Self-injection | 4th follow-up | 5th Follow-up | 6th Follow-up | 7th Follow-up |
|---|---|---|---|---|---|---|---|---|---|---|
| At week 6 | At week 8 | At week 10 | At week 12 | At week 16 | At week 20 | At week 24 | ||||
| Patients screened & recruited | Blood parameters assessed | Effectiveness parameters were analyzed | Blood parameters assessed | 80 mg s/c injection | Blood parameters assessed | 80 mg s/c injection | Blood parameters assessed | Blood parameters assessed | Blood parameters assessed | Blood parameters assessed |
| Blood investigation done | A loading dose of 160 mg subcutaneous injection given | 80 mg s/c injection was given | Effectiveness parameters were analyzed | Effectiveness parameters were analyzed | Effectiveness parameters were analyzed | Effectiveness parameters were analyzed | Effectiveness parameters were analyzed | Effectiveness parameters were analyzed | ||
| 80 mg s/c injection was given | 80 mg s/c injection was given | 80 mg s/c injection was given | 80 mg s/c injection was given | 80 mg s/c injection was given | Final Outcome measured |
Out of the 22 patients, 14 (63.6%) were male patients and 8 (36.4%) were female patients. The age of the patients varied between 22 and 56 years (Mean +/− standard deviation (SD) = 36.72 ± 8.28 years), Median 37 years. The mean duration of illness was 7.36–4.29 years, ranging from 2-16 years; the Median was 6.5 years. 31.8% of patients had pre-existing comorbidity like Hypertriglyceridemia (3, 13.6%), Hypertension (2, 9.1%), and TB-gold positive (2, 9.1%). One of the patients was HIV positive with no signs/symptoms of AIDS. All these patients had moderate to severe psoriasis inadequately responding to at least two systemic immunodulators or one or two biologics. 16 (72.7%) patients were previously prescribed methotrexate and/or cyclosporin at 3-5 mg/kg body weight for a minimum of 3 months at some point in their disease. Four patients had a history of secondary Secukinumab failure, and two patients were previously treated with both Adalimumab and Secukinumab with no response. The baseline PASI score in these patients varied from 48 to 20, with the Mean ± SD PASI being 30.82 ± 7.06. After 24 weeks of treatment mean PASI improved to 2.82 ± 3.12, ranging from 6 to 0 [Table 2]. The mean PASI reduction at week 24 was 90.9% from baseline. Achievement of PASI 75 by patients in the 4th week was only 13.6%. But in the 12th week, PASI 75 and PASI 90 were achieved by 86.4% and 31.8% of patients respectively. At the end of treatment (7th follow-up visit), PASI 75 was achieved by 95.45% of patients, PASI 90 was achieved by 68.18% of patients, and PASI 100 was achieved by 27.27% of patients. Baseline BSA involved varied from 14-40, with the Mean ± SD BSA being 27.18 ± 8.05. After 24 weeks of treatment mean BSA improved to 1.41 ± 1.56, ranging from 3 to 0 [Table 1].
Table 2.
Evaluation of efficacy of Ixekizumab with PASI, BSA and sPGA scores
| Baseline | V3 | V4 | V5 | V6 | V7 | V8 | V9 | |
|---|---|---|---|---|---|---|---|---|
| PASI | ||||||||
| Mean±SD | 30.82±7.06 | 19.68±4.96 | 11.27±3.03 | 7.09±3.31 | 5.22±3.00 | 3.95±3.36 | 3.27±3.32 | 2.82±3.12 |
| Range | (48-20) | (28-11) | (17-7) | (16-3) | (14-1) | (8-0) | (8-0) | (6-0) |
| BSA | ||||||||
| Mean±SD | 27.18±8.05 | 17.50±5.14 | 11.32±4.00 | 6.27±2.70 | 3.50±2.02 | 2.18±1.82 | 1.77±1.79 | 1.41±1.56 |
| Range | (40-14) | (28-10) | (20-4) | (12-1) | (8-1) | (4-0) | (4-0) | (3-0) |
| sPGA | ||||||||
| Mean±SD | 3.55±0.51 | 2.77±0.44 | 2.27±0.70 | 1.55±0.59 | 1.27±0.56 | 1.05±0.66 | 0.81±0.60 | 0.73±0.56 |
| Range | (4-3) | (3-2) | (3-1) | (3-1) | (2-0) | (2-0) | (2-0) | (2-0) |
Baseline sPGA involved varied from 4-3, with the Mean ± SD BSA being 3.55 ± 0.51. After 24 weeks of treatment mean sPGA improved to 0.73 ± 0.56, ranging from 2 to 0 [Table 1]. Friedman’s ANOVA shows a significant decrease (P < 0.05) in PASI, BSA, and sPGA score starting from 1st follow-up (2 weeks) onwards. Paired t-test shows significant decrease in PAsI, BSA, and sPGA reduction P < 0.0001 between baseline and 7th follow-up visit (24 weeks). In our study, only 5 (22.7%) patients developed mild side effects. The most common events included injection-site reaction, i.e., redness, itching, pain, and/or swelling in 2 (40%) patients. Other side effects were nasopharyngitis (1,20%), upper respiratory tract infection (1, 20%), and cellulitis (1, 20%). No cases of inflammatory bowel disease, neutropenia, tuberculosis, or severe bacterial infection were noted. A bar diagram has shown improvement of PASI as per duration of treatment [Figure 1].
Figure 1.
Bar diagram showing improvement of PASI as per duration of treatment
Discussion
Ixekizumab is a humanized IgG4 monoclonal antibody that neutralizes interleukin-17A. It has significant efficacy in treating moderate to severe psoriasis and Psoriatic arthritis. Ixekizumab has been available for the treatment of moderate-to-severe PsO and active PsA since 2016 and 2017, respectively, in the US and from 2022 in India. Ixekizumab had a rapid onset of action, as evidenced by significant reductions in PASI scores by at least 75% or static physician’s global assessment scores of 0 or 1 at week 2 as compared with placebo in the study by Leonardi et al.[8] In our study, we have seen a significant decrease (P < 0.05) in PASI, BSA, and sPGA scores starting from the 1st follow-up (2 weeks) onwards. In a Japanese study, improvement from baseline PASI was observed as early as Week 1.[9] Regarding sPGA score, in the study by Leonardi et al.,[8] 40% of the patients achieved sPGA 1 (near clearance) or 0 (complete clearance) at week 12. Our study has shown far more improvement, like 90.9% (20/22) of patients achieved sPGA 1 or 0 by the 20th week. In a study by Saeki et al.,[9] 98.7% (77/78) of patients achieved PASI75, 83.3% (65/78) achieved PASI 90, and 32.1% (25/78) achieved PASI 100 at Week 12. In a randomized placebo-controlled trial, the PASI75, PASI90, and PASI 100 ratios achieved at week 12 in the ixekizumab-treated group were 89.1% (vs placebo 3.9%), 70.9% (vs placebo 0.5%) and 35.3% (vs placebo 0.0%) in UNCOVER-1 study and 87%, 68% and 38% in UNCOVER-3 study.[13] In our study, at the 20th week, PASI75 was achieved by 91% (20/22) of patients, PASI 90 was achieved by 63.6% (14/22) of patients, and PASI 100 was achieved by 22.7% (5/22) of patients. There is plenty of real-world data available regarding the efficacy of Ixekizumab in psoriasis. Ixekizumab is very safe and could be used in latent tuberculosis. Two TB-gold-positive patients were put on Ixekizumab without any flare of tuberculosis after 6 months of follow-up. In our study, only 5 patients (22.7%) showed mild side effects, where injection site reaction (40%) and nasopharyngitis (20%) were more common. This data is comparable to the study done by Deza et al.[14] where 26% of patients experienced adverse and most common local reactions at the site of injection (53.8%).
The limitations of our study are that it’s a retrospective study. Randomized controlled trials would have been a better option to establish the efficacy of a newer drug. The data regarding the difficult-to-treat areas like nails or scalp are missing. Long-term follow-up is required for a better understanding of remission/relapse rate and safety profile. On the other hand, the strengths of our study are based on data collection from a real-life setting.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
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