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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 39  |  Issue : 2  |  Page : 57-65

Real-life experience of secukinumab injection in difficult chronic plaque-type psoriasis: a multicenter experience


1 Department of Dermatology, Venereology and Leprosy, Affiliated Faculty, Armed Forces Medical College, Military Hospital, Pune, Maharashtra, India
2 Private consultant dermatology clinic, Noida, Uttar Pradesh, India
3 Department of Dermatology, Venereology and Leprosy, INHS, Mumbai, India
4 Department of Dermatology, Venereology and Leprosy, Command Hospital (SC), India
5 Department of Pharmacology, Affiliated Faculty, Armed Forces Medical College, Military Hospital, Pune, Maharashtra, India

Date of Submission08-Mar-2019
Date of Acceptance20-May-2019
Date of Web Publication03-Jul-2019

Correspondence Address:
G K Singh
Department of Dermatology, Venereology and Leprosy, Affiliated Faculty, Armed Forces Medical College, Military Hospital, Kirkee, Pune 411020
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejdv.ejdv_10_19

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  Abstract 


Background Secukinumab, a fully human monoclonal antibody that selectively targets interleukin-17A, has been proven highly efficacious in the management of moderate to severe psoriasis with early response and sustained effects in many phase III clinical trials. However, data on real-life experience is lacking.
Patients and methods A multicentric, retrospective study in routine clinical setting was conducted in cases of chronic plaque type of psoriasis during November 2016 to December 2017. Patients who had received 300-mg secukinumab injection subcutaneously at 0, 1, 2, 3, and 4 months and then every 4 weekly for at least 6 months were recruited for the study. Assessment of severity of psoriasis was done by psoriasis area severity index (PASI) and dermatological life quality index (DLQI).
Results A total of 32 patients, comprising 24 males and 8 females, with mean age of 42.31 years (SD 11.32) and mean baseline PASI of 20.72 (SD 7.53) and DLQI of 15.31 (SD 5.25), were studied. Achievement of PASI 75/90/100 at 12 weeks was 81.25/59.37/9.3, respectively. PASI 75 at the end of 52 weeks was maintained at 65.62. DLQI reduced to 2.56 (SD 5.19) (16.72% of baseline) at the end of 12 weeks. Differences between baseline scores and each subsequent visit were statistically significant (P<0.001). Only mild adverse effects were noticed in six (18.7%) patients.
Conclusion Secukinumab is a very promising new molecule in the management of chronic plaque type of psoriasis that is resistant to conventional modalities in routine clinical setting even in an Indian scenario. A retrospective analysis, with few cases, was inherent limitation of this study.

Keywords: chronic plaque psoriasis, dermatological life quality index, psoriasis area severity index, secukinumab


How to cite this article:
Singh G K, Sekhri R, Chatterjee M, Baveja S, Akhoon N. Real-life experience of secukinumab injection in difficult chronic plaque-type psoriasis: a multicenter experience. Egypt J Dermatol Venerol 2019;39:57-65

How to cite this URL:
Singh G K, Sekhri R, Chatterjee M, Baveja S, Akhoon N. Real-life experience of secukinumab injection in difficult chronic plaque-type psoriasis: a multicenter experience. Egypt J Dermatol Venerol [serial online] 2019 [cited 2019 Jul 23];39:57-65. Available from: http://www.ejdv.eg.net/text.asp?2019/39/2/57/262032




  Introduction Top


Psoriasis is a chronic, immune-mediated inflammatory disorder having a relapsing and remitting course that affects 0.2–8.5 % of world population [1],[2],[3]. In India, the prevalence of psoriasis varies from 0.44 to 2.8%, and it is twice more common in males compared with females [4]. In the long run, it severely impairs quality of life of affected individuals [5]. Psoriasis is now considered to be a systemic disease. It is more prevalent in persons with metabolic syndrome and known to have cardiovascular risk factors [6],[7]. It is thought that proinflammatory cytokine interleukin (IL)-17A − produced by a subset of T helper cells, as well as by other innate and adaptive immune cells − plays a key role in pathophysiology of psoriasis. The current evidence suggests that IL-23/Th17 axis appears to be crucial in the pathogenesis of psoriasis, and its inhibition seems to be central to therapeutic achievement [8],[9],[10],[11],[12]. There are subsets of patients with chronic plaque type of psoriasis who require biologic therapies for better control of disease. Presently, dermatologists worldwide choose among five commonly approved biologic therapies that fall into three classes: the tumor necrosis factor alpha inhibitors (etanercept, infliximab, and adalimumab), the IL-12/IL-23 inhibitors (ustekinumab), and an IL-17 inhibitor (secukinumab) [13]. The biologics currently in use for psoriasis in India are etanercept, infliximab, adalimumab (biosimilar), itolizumab, and the recently introduced secukinumab [14]. Secukinumab, a fully human monoclonal antibody that selectively targets IL-17A, has been proven highly efficacious in the treatment of moderate to severe psoriasis, starting at early time points, with a sustained effect [15],[16],[17],[18],[19],[20]. This study was undertaken to evaluate the real-life experience of use of secukinumab injection in difficult chronic plaque type of psoriasis cases in the scenario of the Indian subcontinent.


  Patients and methods Top


This was a retrospective, multicentric, study to know the efficacy and safety of 300-mg secukinumab injection administered subcutaneously at 0, 1, 2, 3, and 4 months and then every 4 weekly for at least 6 months in cases of chronic plaque type of psoriasis in routine clinical setting. The dose schedule was based upon schedules tried in multiple clinical trials. Data were also analyzed at the end of 52 weeks of therapy. Written consent from patients where applicable and approval from ethics committee of institution were taken before analyzing the data into the study. The study period was between November 2016 and December 2017 at three dermatology centers across India.

Patients were 18 years of age or older with moderate to severe plaque psoriasis who had been diagnosed at least 1 year before and were poorly controlled with topical treatments, phototherapy, systemic therapy including biologicals, or a combination of these therapies. In addition, patients had a score of 10 or higher on the psoriasis area and severity index (PASI). The study also included those in whom alternative standard systemic therapies were contraindicated or there was a history of intolerance or unresponsiveness to the standard systemic therapy. Patients with forms of psoriasis other than chronic plaque type psoriasis or HIV positive, infective hepatitis, having active tuberculosis, received any other systemic drug or history of taken secukinumab earlier, were excluded from the study. Records of physical examination which included examination of oral and genital mucosa at baseline and each visit were also analyzed. Topical emollient and topical steroid alone or in combination with salicylic acid were continued in these patients. All patients had undergone complete blood count, urine analysis, liver function test with enzymes, blood sugar, blood urea, serum creatinine, chest radiography, and Mantoux tests at baseline. Blood test and urine analysis were repeated at 3-month interval. Systemic agents including biological if any were stopped 1 week before administration of secukinumab. Secukinumab injection was not continued if the patients failed to achieve PASI 75 even after 6 months of therapy. However, these patients were offered other modalities of therapies. After 6 months of regular secukinumab therapies, patients were administered this injection as on required basis till 52 weeks.

Patient severity was assessed by PASI [21] (a composite evaluation instrument for psoriasis severity, with subscores for erythema, induration, scaling, and percentage of body-surface area affected), and qualitative measures were assessed by dermatological life quality index (DLQI) [22], a validated instrument for dermatologic conditions (scores range from 0 to 30 points, with higher scores indicating a greater effect on quality of life) at each visit. Efficacy of drug was evaluated by observed change in PASI and DLQI score since baseline. PASI/DLQI scores were noted at baseline and at an interval of 1 till 6 months. Patients were followed up for another 6 months. Statistical analysis was done by IBM SPSS Statistics for Windows, version 23.0. (SPSS Inc., New York, New York, USA). Differences in parametric measures were tested by using t tests, whereas for nonparametric measures, Wilcoxon signed-rank test was done to know the statistical outcome. P value less than 0.05 was considered statistically significant.


  Results Top


Thirty two patients (North India, 18; West India, 08; and South India, 06), comprising 24 males and 8 females, with mean age of 42.31 years (SD 11.32) and mean baseline PASI of 20.72 (SD 7.53) were studied; they all fit into our inclusion criteria. Mean duration of psoriasis present in the patients was 7.78 years (SD 6.26). A total of 26 patients (81.25%) did not require application topical steroid or steroid plus salicylic acid combination after mean duration of 7.9 weeks (SD 1.74). Data of each patient on secukinumab for difficult chronic plaque psoriasis were well maintained at each center. Each patient had visited hospital/clinics every month till 52 weeks. Six patients could not stop topical application of steroid/steroid salicylic acid combination as multiple thick plaques persisted even at the end of 6 months of therapy. These six patients did not achieve PASI 75 even after 6 months of therapy. Overall, 19 (59.37%) patients had comorbidities. Obesity and hypertension were common comorbidities. Every patient had received at least two or more than two systemic therapies in the past. Twenty (62.5%) patients had received biologics earlier. The detail general profile of patients including their age, sex, past treatment, comorbidities, baseline PASI and DLQI, requirement of topical therapy, and adverse effects noted during course of therapy and follow-up is illustrated in [Table 1]. Mean baseline PASI (20.72, SD 7.53) and mean baseline DLQI (15.31, SD 5.25) gradually declined till six visits to become 2.75 (SD 5.9) and 2.28 (SD 6.61), respectively. Since discontinuation of secukinumab at monthly interval after 6 months, mean PASI and DLQI raised to 5.95 (SD 7.82) and 4.31 (SD 5.55) at the end of 52 weeks, respectively. Reduction in PASI and DLQI in each subsequent visit was statistically significant (P<0.001). After 6 months of regular secukinumab, mean interval on which rest of patients were administered secukinumab was 6.7 weeks (SD 1.70). Details of PASI and DLQI of each patient at each visit and their percentage reduction in comparison with baseline are depicted in [Table 2]. There was rapid achievement of PASI 100/90/75/50 in each subsequent visit till 6 months. However, it starts declining after 6 months once patient was not on regular secukinumab therapy. After 6 months, those who did not achieve PASI 75, this drug was stopped and conventional modalities were restarted. Number of patients who had achieved PASI 100/90/75/50 at different visits is depicted in a [Figure 1]. There was sharp reduction in mean PASI and DLQI score by the end of 6 months, which gradually start rising by the end of year when patient was not on regular secukinumab. How mean PASI and DLQI reduced in each visit is depicted in [Figure 2]. Adverse effects were very mild in nature, noticed only in six (18.7%) patients. These were postinjection itching (n=2; 6.25%), folliculitis seen over lower legs and thighs (n=2; 6.25%), upper respiratory tract infection (n=1; 3.12%), and injection site pain in both the thighs (n=1; 3.12%). These did not require stoppage of therapy. Upper respiratory tract infection was treated by short course of oral antibiotic. There was no case of oral or genital candidiasis noted. No abnormality was detected in follow-up of laboratory parameters. There was significant reduction in erythema, scaling, and induration of psoriatic plaques by the end of 6 months barring six patients. Pretherapy and posttherapy images of two such patients who had shown very good response are illustrated in [Figure 3],[Figure 4],[Figure 5].
Table 1 General clinical profile of patients of psoriasis vulgaris (chronic plaque type)

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Table 2 Mean differences in the score of psoriasis area severity index and dermatological life quality index at baseline, after 1 month (visit 1), 2 months (visit 2), 3 months (visit 3), 4 months (visit 4), 5 months (visit 5), 6 months (visit 6), and at end of year (visit 7) with P value

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Figure 1 Achievement of PASI 100/90/75/50 by the patients at different visits. PASI, psoriasis area severity index.

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Figure 2 Progression of mean PASI and DLQI of patients at different visits. DLQI, dermatological quality of life index; PASI, psoriasis area severity index.

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Figure 3 Pretherapy and posttherapy images of a patient on secukinumab.

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Figure 4 Pretherapy and posttherapy images of a patient on secukinumab.

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Figure 5 Pretherapy and posttherapy images of a patient on secukinumab.

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  Discussion Top


The conventional or traditional systemic drugs used in psoriasis over a prolonged period of time are known to have poor compliance, unsatisfactory results, systemic toxicity and adverse effects that necessitate either change or stoppage of therapies. There are subsets of patients who require newer modalities of therapies to control ongoing psoriasis. For India and countries of Indian subcontinent being resource poor, the dermatologists have to balance the disease control in patients and the budgetary implication of therapies. Emergence of targeted therapy (biological) for psoriasis has started a new era and newer hope in the management of chronic plaque type of psoriasis. In routine clinical setting, patients are prescribed emollient and topical steroid/steroid salicylic acid combination agents for better compliance and long-term management of psoriasis. At many occasions when patients do not achieve PASI 75 even after 6 months of therapy or earlier, dermatologists add conventional therapies along with biologic.

Secukinumab, a fully human monoclonal antibody that selectively targets IL-17A, is associated with a rapid reduction in psoriasis symptoms, elicited significantly greater PASI 75 rates and higher rates of 0 or 1 responses on the modified investigators global assessment than placebo at week 12, and with continued treatment was associated with sustained high response rates in a majority of patients through week 52 in different initial clinical trials [15],[16],[17],[18],[19],[20].

In our retrospective study, PASI 75/90/100 reduction at 12 weeks was 81.25%/59.37%/9.3%. In more scientific study like the ERASURE study, PASI 75/90/100 reduction at 12 weeks were 81.6%/59.2%/28.6% with 300 mg of secukinumab, whereas in the FIXTURE study, the rates were 77.1%/54.2%/24.1%. In the JUNCTURE study at 12 weeks with secukinumab 300 mg, PASI 75/90/100 were achieved by 81.4/64.1/38.8%, respectively. Except PASI 100, rest of the other results were like other studies. In Indian patients, which were part of FIXTURE study [23], PASI 75/90/100 reduction at 12 weeks were 61%/41.5%/14.6% which is more close to the findings of our study.

In our patients, at the end of 52 weeks, PASI 75 reduction rate was 65.62. In comparison, in the ERASURE and FIXTURE studies, maintenance of PASI 75 from 12 weeks till 52 weeks were 80.5 and 84.3, respectively. In Indian patients who were part of FIXTURE study, [23] maintenance of PASI 75 from 12 weeks till 52 weeks was 95.1%. The better PASI 75 maintenance in other studies can be explained by continuation of injection secukinumab even after 6 months of therapy. However, in our patients, only six patients who continued to require emollient or steroid/steroid salicylic acid combination were not continued on secukinumab; instead, they were administered tab methotrexate weekly. Five out of six had comorbidity of obesity. Failure of therapies in them could be multifactorial. These cases were already difficult ones who have failed conventional modalities, even biological earlier. Comorbidities like obesity and risk factor like smoking, alcohol, or stress are known to have poor outcome in such scenarios. Data on history of smoking, alcohol, and stress were not reliable, so they cannot be emphasized on our patients.

At baseline, mean DLQI of our patient was 15.31 (SD 5.25), which gradually reduced to 2.56 (SD 5.19) (16.72% of baseline) at the end of 12 weeks. DLQI in the ERASURE study reduced from 13.9 to 2.5 (17.9% of baseline) at 12 weeks, whereas in the FIXTURE study. It reduced from DLQI 13.1 from baseline to 2.9 (22.1% of baseline) at 12 weeks. In Indian patients who were part of FIXTURE study, [23] DLQI reduction at 12 weeks was 10.9% of baseline. These results were comparable to our study.

Overall, 26 (81.25%) patients did not require applying topical steroid or steroid plus salicylic acid combination after mean duration of 7.9 weeks (SD 1.74). After 6 months of regular secukinumab, mean interval on which rest of patients were administered secukinumab was 6.7 weeks (SD 1.70). This comparison could not be done to other studies as these were placebo-controlled trials.

In our study, adverse effects were very mild in nature, noticed only in total six (18.7%) patients. No patient developed any serious adverse effect which required discontinuation of therapy. The proportion of patients experiencing adverse events was much greater with secukinumab 300 mg, varying between 55 and 88% in different clinical trials [15],[16],[17],[18],[19],[20]. During the entire treatment period, in Indian patients who were part of FIXTURE study [23], the frequency of treatment-emergent adverse effects was higher in secukinumab (53.6%) group. Over the entire treatment period, 4.7% of the 300 mg secukinumab group in FIXTURE study reported mild or moderate Candida spp. infection. Unlike clinical trial data, no candidial oral/genital infection was observed in our group of patients. Higher adverse effects could be explained by more stringent reporting of double-blinded placebo-controlled trial and longer duration of injection secukinumab. Comment on newer intuitive assessment tool which is utilized for clinical trial ‘five-point investigator global assessment’ [24] and drug antibody test cannot be elicited as these were not available in our patients. Less number of patients, retrospective, uncontrolled study and only 24 weeks follow-up data were the limitations of this study. We did use topical therapies and intralesional kenacort if required along with secukinumab, which was usually practiced by dermatologists in routine clinical setting. How much differences these topical/intralesional drugs made on the efficacy could not be commented as there was no other controlled group. However, in routine clinical practice, even though patients are on biological drugs, they are continued on topical steroid with salicylic acid combinations and emollient. The authors noticed that resistant plaques that did not respond to secukinumab showed complete disappearance after administering intralesional triamcinolone. As per the recommendations of multiple clinical trials [16],[17],[18],[19], continuation of therapy even after 6 months is recommended. Therefore, clinical efficacy would have been better if we would had continued the secukinumab on monthly dosages even after 6 months.Secukinumab is very promising new molecule in the management of chronic plaque type of psoriasis that are resistant to conventional modalities in the scenario of Indian subcontinent. Like any other biologics, secukinumab therapy also requires continuation to sustain efficacy and avoid frequent relapses. Nevertheless, it requires large number of such patients with randomized, double blind placebo, controlled trial, and long-term follow-up data to convincingly prove that this drug is very effective in aforementioned dose regimen in chronic plaque type of psoriasis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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