Indian Journal of Drugs in Dermatology

ORIGINAL ARTICLE
Year
: 2019  |  Volume : 5  |  Issue : 1  |  Page : 14--18

Real-life efficacy and safety of secukinumab: A single-center, retrospective observational study with 52-week follow-up


Shekhar Neema1, S Radhakrishnan1, Sehdev Singh2, Biju Vasudevan3, Manas Chatterjee4,  
1 Department of Dermatology, Armed Forces Medical College, Pune, Maharashtra, India
2 Department of Dermatology, Command Hospital, Kolkata, West Bengal, India
3 Department of Dermatology, Base Hospital, Lucknow, Uttar Pradesh, India
4 Department of Dermatology, INHS, Asvini Mumbai, Maharashtra, India

Correspondence Address:
Dr. Shekhar Neema
Armed Forces Medical College, Pune, Maharashtra
India

Abstract

Background: Secukinumab is a fully human monoclonal antibody against interleukin-17. Phase III trials have shown encouraging results in chronic plaque psoriasis. The real-life data for safety and efficacy of secukinumab are limited. Methodology: This was a retrospective, single-center, observational study conducted in a tertiary care center of East India between January 2016 and December 2017. Patients with chronic plaque psoriasis who were initiated on injection secukinumab during the study period and completed 52 weeks of observation period were included in the study. Analysis was performed using SPSS version 25. Results: Twenty patients were recruited in the study. Mean age of the patients was 46 years and mean duration of disease was 11 years. Eleven (55%) patients were biologic experienced and Nine (45%) patients were biologic naïve. Mean Psoriasis Area and Severity Index (PASI) score at baseline was 17.05 (±6.7). Fifteen (75%) patients achieved PASI75 at 4 weeks. Seventeen (85%) patients achieved PASI75, 13 (65%) achieved PASI90, and 10 (50%) patients achieved PASI100 at 12 weeks. Eighteen (90%), 10 (50%), and 7 (35%) patients maintained PASI75, PASI90, and PASI100 response, respectively, at the end of 52 weeks. Adverse effects were seen in 6 (30%) patients over 52 weeks. Drug discontinuation was required because of severe exacerbation of eczema and recalcitrant vulvovaginal candidiasis in one patient each. Conclusion: Secukinumab is an effective drug for the management of chronic plaque psoriasis even in patients who have previously been treated with systemic drugs and other biologics; however, adverse effects are more common as compared to what trial data suggest. Limitations of Study: Small sample size and retrospective study design are main limitations of the study. Strength of Study: This is first real-life data with 52 weeks follow up from India.



How to cite this article:
Neema S, Radhakrishnan S, Singh S, Vasudevan B, Chatterjee M. Real-life efficacy and safety of secukinumab: A single-center, retrospective observational study with 52-week follow-up.Indian J Drugs Dermatol 2019;5:14-18


How to cite this URL:
Neema S, Radhakrishnan S, Singh S, Vasudevan B, Chatterjee M. Real-life efficacy and safety of secukinumab: A single-center, retrospective observational study with 52-week follow-up. Indian J Drugs Dermatol [serial online] 2019 [cited 2019 Oct 19 ];5:14-18
Available from: http://www.ijdd.in/text.asp?2019/5/1/14/263099


Full Text



 Introduction



Psoriasis is a T-cell-mediated idiopathic disorder affecting 1%–3% of the general population. Psoriasis was initially thought to be a disease driven by keratinocyte proliferation. The understanding of the pathogenesis of psoriasis is increasing at a rapid pace, and the role of the immune system and T helper 1 (Th1) cells has been recognized. The development of therapeutics has kept pace with these developments and resulted in newer targeted therapies. Biologics are protein molecules which target specific parts of the immune system. There are various biologics available for the management of psoriasis targeting different cytokines. The tumor necrosis factor-alpha (TNF-alpha) inhibitors are etanercept, infliximab, and adalimumab. Interleukin-12/23 (IL-12/23) inhibitor is ustekinumab. IL-17 inhibitors are secukinumab, brodalumab, and ixekizumab, and IL-23 inhibitors are guselkumab and tildrakizumab.

Secukinumab is a monoclonal antibody against IL-17A and was approved by the United States Food and Drug Administration for the treatment of chronic plaque psoriasis in January 2015. The dose of secukinumab for the treatment of chronic plaque psoriasis is 300 mg weekly for 5 weeks, followed by monthly doses of 300 mg. Phase III studies have shown the Psoriasis Area and Severity Index 75 (PASI75) (75% improvement in PASI) response in 77%–80% of patients at week 12 and PASI90 and PASI100 response in 55%–59% and 24%–28% of patients, respectively. Almost 80% of patients maintained PASI75 till week 52.[1] Data from Phase III trials and extension of these Phase III trials suggest that secukinumab results in rapid and sustained improvements in psoriasis. Common adverse effects seen during Phase III trials were nasopharyngitis, upper respiratory tract infection, and headache. Candida infection was also seen more commonly in patients on secukinumab. Phase III trials excluded patients who were on methotrexate or any other immunomodulating treatment or required washout period of 4 weeks before randomization. However, in practice patients are started on secukinumab after failure or intolerance of systemic therapy. In many cases, patients have also experienced other available biologics before being given secukinumab. In view of the above, we conducted a retrospective observational single-center study to know the efficacy and adverse effects of secukinumab in a real-life scenario.

 Methodology



This study was a retrospective uncontrolled observational study conducted in a tertiary care dermatology center of East India. The period of study was between January 2016 and December 2017. Ethical committee clearance was obtained. Patients with chronic plaque psoriasis who were initiated on secukinumab and completed 52 weeks of continuous therapy were included in the study. Exclusion criteria were use of secukinumab other than approved dose of 300 mg Period of observation was 52 weeks after initiation of therapy.

Demographic and clinical data (age, sex, duration of disease, and comorbidities) for each patient were collected. Previous treatment and adverse events in respect of previous treatment were also noted. Secukinumab was administered in the standard dosing regimen (300 mg subcutaneously weekly for 5 weeks and once a month thereafter for total of 52 weeks unless it was required to be stopped due to adverse effect or poor efficacy). Severity assessment was done at baseline, week 4, week 12, week 26, and week 52. The primary end point was PASI75 at week 12. Secondary end points were PASI75 and PASI100 at week 52 and adverse events during follow-up period. Based on previous treatment, patients were divided into two groups of biologic naïve and experienced.

Serology for hepatitis B, hepatitis C, and HIV, Mantoux test, chest X-ray, complete blood count (CBC), blood urea, creatinine, lipid profile, fasting and postprandial glucose, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were done at baseline. CBC, ALT, AST, blood urea, and creatinine were repeated at weeks 4, 12, 24, 36, and 52.

Data were analyzed by an intent to treat last observation carried forward imputation, where if a patient discontinued therapy because of adverse effects, the last available value was carried forward until the end of the treatment. Data were presented as mean ± standard deviation. The significance in difference between the two groups was assessed using unpaired t-test. P < 0.05 was considered as statistically significant. Analysis was performed using Statistical Package for the Social Sciences (SPSS) ver 25, IBM Corporation, USA.

 Results



Twenty-three patients were assessed for inclusion in the study. Three patients were given 150 mg of secukinumab and hence were excluded from the study. Thus, twenty patients were recruited in the study. Demographic data are given in [Table 1]. Mean age of the patients was 46 years and mean duration of disease was 11 years. Psoriatic arthritis was seen in 7 (35%) percent patients, Type 2 diabetes mellitus in 3 (15%) and hypertension in 6 (30%) patients. [Table 2] shows comorbidities, treatment already taken by the patients, and reason to switch. All patients were given some form of systemic therapy before being given secukinumab. Nine patients were biologic naïve while 11 patients were biologic experienced. Two patients had taken more than one biologic before being given secukinumab.{Table 1}{Table 2}

[Chart 1] shows efficacy of secukinumab. Mean PASI score at baseline was 17.05 (±6.7). Fifteen (75%) patients achieved PASI75 at 4 weeks [Figure 1]a [Figure 1]b, [Figure 1]c, [Figure 1]d, [Figure 1]e,[Figure 1]f. Seventeen (85%) patients achieved PASI75, 13 (65%) achieved PASI90, and 10 (50%) patients achieved PASI100 at 12 weeks [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d. At the end of 52 weeks, 18 (90%), 10 (50%), and 7 (35%) patients maintained PASI75, PASI90, and PASI100, respectively [Figure 3]a, [Figure 3]b, [Figure 3]c, [Figure 3]d, [Figure 3]e, [Figure 3]f, [Figure 3]g, [Figure 3]h.{Figure 1}{Figure 2}{Figure 3}[INLINE:1]

[Table 3] shows adverse effects seen with therapy [Figure 4]a, [Figure 4]b, [Figure 4]c, [Figure 4]d. Adverse effects were seen in 6 (30%) patients over 52 weeks. Drug discontinuation was required because of severe exacerbation of eczema and recalcitrant vulvovaginal candidiasis in one patient each after 32 weeks and 24 weeks, respectively.{Table 3}{Figure 4}

 Discussion



Secukinumab is first in class monoclonal antibody against IL-17. Since IL-17 is found to be a key mediator in the pathogenesis of psoriasis, it is not surprising that secukinumab is very effective in the management of psoriasis. Phase III studies and pooled data analysis show that secukinumab has a favorable safety profile, and patients achieved sustained remission while on secukinumab.[2] Although the trial data for efficacy of secukinumab are encouraging, the availability of real-life data is limited. Egeberg et al. utilized Danish registry data to evaluate safety, efficacy, and drug survival (time to discontinuation) of biologics in patients with moderate-to-severe chronic plaque psoriasis. The study concluded that though secukinumab had the highest number of patients achieving PASI100, it had the lowest survival and highest number of adverse events, predominantly infections.[3] Huang et al. reported the outcome in 90 patients initiated on fixed interval secukinumab (300 mg) in a real-life setting, and discontinuation of therapy was reported in 27 out of 90 patients due to inefficacy or adverse effects. Follow-up period in the above study was 32 weeks, and 57% of patients maintained efficacy during follow-up period. Thirteen patients showed loss of efficacy and all of them were biologic experienced. Eighty-seven (90%) patients had experienced previous systemic therapy and 81 (90%) of patients had experienced previous biologic therapy in this study.[4] This scenario more closely mimics real-life situation as compared to trial data, where most of the patients have experienced some form of systemic therapy. In our study, all patients have experienced systemic therapy; 11 (55%) patients were biologic nonnaïve and 2 (10%) patients had been given two or more biologics before starting secukinumab. Another real-life efficacy and safety study conducted in a tertiary hospital in Greece on 42 patients corroborated the findings of Phase III studies. They found secukinumab to be more efficacious than Phase III studies and found complete clearance in most patients after the third injection. Adverse effects were also noted in three patients, and discontinuation was required only in one patient. However, mean baseline PASI in this study was 6.7, and the previous treatments administered to patients are also not mentioned.[5] Galluzzo et al. conducted a multicentric real-life study in Italy which included 107 patients and 52-week observation period. At week 4, 58% of patients achieved PASI75, 35.5% PASI90, and 22.4% PASI100. At week 52, data were available for 35.5% (38/107) of patients. About 92.1% (35/38), 81.6% (31/38), and 78.9% (30/38) of patients maintained PASI75, PASI90, and PASI100, respectively. At week 4, PASI75 response was achieved by 60% of biologic-naïve patients while 41.2% of biologic-experienced patients achieved PASI75. Nearly 9.3% (10/107) of patients experienced adverse effects, most common of which was mucocutaneous candidiasis. Thirteen percent (14/107) of patients discontinued secukinumab due to inefficacy, 1 patient due to primary inefficacy, 11 patients due to secondary inefficacy, and 2 patients due to worsening of psoriatic arthritis. In two patients, secukinumab was discontinued due to the development of mucocutaneous candidiasis and inefficacy of antimycotic therapy.[6]

In the present study, 100% of patients were followed up for 52 weeks. At 4 weeks, 75% (15/20) of patients achieved PASI75, and at week 52, 90% (18/20) maintained PASI75. Thirty-five percent of patients (7/20) maintained PASI100 at week 52. The higher percentage of patients maintained PASI75/90/100 at the end of week 52 in the biologic-naïve group; however, the difference was not statistically significant possibly due to the small sample size [Table 4]. Thirty percent of patients (6/20) developed adverse effects during the course of therapy, out of which two required discontinuation of therapy. Adverse effects were also more common in biologic-experienced patients. Two patients developed injection site reaction which was managed conservatively, and one patient developed widespread dermatophytosis 6 weeks after initiation of therapy and was treated with a course of itraconazole. One patient (patient 13), a 46-year-old female, known diabetic, developed vulvovaginal candidiasis; 16 weeks after starting secukinumab, she continued to be symptomatic for candidiasis despite therapy and required drug discontinuation at 24 weeks. Another patient (patient 14), a 58-year-old male, developed severe eczema involving both the legs; there was no improvement despite adequate treatment and required drug discontinuation at 32 weeks [Figure 4]a and [Figure 4]b. Paradoxical development of psoriasis has been reported with TNF-alpha inhibitors and has also recently been reported with secukinumab.[7] However, exacerbation or precipitation of eczema by secukinumab has not been reported. It could have occurred possibly due to Th1/Th2 imbalance which occurs due to biologic administration. One patient (patient 11) developed loss of response 8 months after starting therapy since the estimation of trough level of secukinumab as well as antidrug antibodies (ADAs) was not available. We assume that secondary inefficacy is due development of ADA, and hence, mycophenolate mofetil was introduced to suppress the formation of ADA. With this, the patient regained control of the disease, and we could continue secukinumab in the same dose. Phase III trials detected the development of ADA in 0.4% of patients, and these antibodies were nonneutralizing antibodies. However, even nonneutralizing ADA can reduce the efficacy by increasing the elimination of drug by the formation of antigen–antibody complexes.[1],[8] The use of methotrexate can reduce the formation of ADA. Other immunosuppressive drugs have also been used to reduce or eliminate the formation of ADA and restore clinical response in case of secondary failure in inflammatory bowel disease, but it has not been used in psoriasis.[9] We used mycophenolate mofetil and effectively restored clinical response to secukinumab in one case. None of the patient required drug discontinuation due to poor efficacy or primary non-response.{Table 4}

 Conclusion



Secukinumab is a novel treatment available for the treatment of chronic plaque psoriasis. It has a rapid onset of action and provides consistent results. Due to lack of insurance coverage and economic factors, biologics for chronic plaque psoriasis in our country are underutilized. Real-life data on secukinumab from our country are lacking, and to our knowledge, there has been no study till date on real-life efficacy and safety of this drug. Secukinumab is an effective drug and gives an opportunity to physicians to bring even recalcitrant psoriasis under control if used properly.

Limitations of the study

This study was conducted in a single center and it was retrospective in nature and had a small sample size.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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