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 Table of Contents  
VIVA VOCE
Year : 2019  |  Volume : 5  |  Issue : 2  |  Page : 118-120

Secukinumab in psoriasis


1 Department of Dermatology, Command Hospital (Eastern Command), Kolkata, West Bengal, India
2 Department of Dermatology, NKP Salve Institute of Medical Sciences, Lata Mangeshkar Hospital, Nagpur, Maharashtra, India

Date of Web Publication16-Dec-2019

Correspondence Address:
Dr. Sushil Pande
Department of Dermatology, NKP Salve Institute of Medical Sciences, Lata Mangeshkar Hospital, Digdoh Hills, Hingna, Nagpur - 440 019, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdd.ijdd_62_19

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How to cite this article:
Chatterjee CM, Pande S. Secukinumab in psoriasis. Indian J Drugs Dermatol 2019;5:118-20

How to cite this URL:
Chatterjee CM, Pande S. Secukinumab in psoriasis. Indian J Drugs Dermatol [serial online] 2019 [cited 2020 Jul 9];5:118-20. Available from: http://www.ijdd.in/text.asp?2019/5/2/118/272966




  What are the Indications for Which You Have Used Secukinumab? Top


Dr. Manas Chatterjee

According to my clinical experience, I have used it in plaque psoriasis, nail/palmoplantar involvement with or without psoriatic arthropathy.

Dr. Sushil Pande

I have used secukinumab mostly in patients of chronic plaque psoriasis and in patients of psoriatic arthritis. I have not used it for indications other than psoriasis ankylosing spondylitis for which also it is approved.[1]


  What are the Clinical Scenarios in Psoriasis Where You Will Prefer Secukinumab over Other Systemic Immunosuppressants Such as Methotrexate or Cyclosporine? Top


Dr. Manas Chatterjee

I prefer secukinumab over systemics in chronic plaque psoriasis cases, especially those who present with severe involvement of body surface area, psychologically disturbed/impairment of quality of life, metabolic comorbidities, alcohol users, etc., Furthermore, psoriatic arthropathy is another frequent consideration in my practice for choosing secukinumab over systemics for preventing radiographic progression.[1] Whenever a patient wants rapid results and desires complete clearance (PASI 100), I go to this drug.

Dr. Sushil Pande

We have used secukinumab in patients of moderate-to-severe plaque psoriasis in adults mostly as a second-line therapy. When conventional and commonly used systemic drugs such as methotrexate, cyclosporine, and azathioprine have failed to control the disease or these therapies have contraindicated in patients due to side effects, secukinumab was used as an ideal biological. Furthermore, when psoralen ultraviolet A (UVA) or narrowband (NB) phototherapy is contraindicated or failed or not feasible for patients despite some good results, we have used secukinumab. It was also used in one patient of nail psoriasis which was refractory to all therapies including etanercept. We have not used secukinumab in patients of widespread and severe life-threatening generalized pustular psoriasis and psoriatic erythroderma. Secukinumab was not used as a first-line therapy.


  Which Forms of Psoriasis Give Unsatisfactory Results to Secukinumab According to You? Top


Dr. Manas Chatterjee

Although secukinumab is approved for usage in plaque psoriasis, a plethora of clinical data exist regarding usage in erythrodermic, pustular, palmoplantar, etc., Erythrodermic cases with changed disease morphology of overlapping multiple phenotypes are the difficult ones to treat. Certain other forms of psoriasis which are type I interferon mediated cutaneous reactions such as guttate psoriasis and others, some forms of pustular psoriasis such as familial generalized pustular psoriasis which are mediated by mutation in interleukin-36 (IL-36) receptor antagonist, also respond less optimally to secukinumab. Marked obesity also sometimes plays a major role in unsatisfactory or less results with secukinumab,[2] since this is a drug which is not dosed by body weight, although uptitration of secukinumab dosage works well.

Dr. Sushil Pande

Patients of moderate-to-severe chronic plaque psoriasis respond best to secukinumab therapy.


  What are Prerequisites and Monitoring Guidelines for Secukinumab Use in Psoriasis? Top


Dr. Manas Chatterjee

The prescreening protocol is similar for secukinumab as compared to other biological immunomodulators. In general, for ruling out latent tuberculosis (TB), we do Mantoux test, chest X-ray, and interferon-gamma release assay (IGRA) as a routine protocol. Although Mantoux test can give false-positive results due to BCG vaccination or is altered by chronic usage of immunosuppressants, IGRA is the choice with high specificity for latent TB. As per Indian recommendations, if latent TB infection is positive, the protocol is to start isoniazid 300 mg and rifampicin 450 mg (if body weight <60 kg) or rifampicin 600 mg (if body weight >60 kg) for 4 months before starting any biologics. However, practically, after 1 month of starting antituberculous treatment (ATT), biologics can be initiated along with an ongoing ATT regimen. Erythrocyte sedimentation rate and complete blood count (CBC) are also helpful for ruling out hidden infections if any. All biologics are contraindicated in active infection, thus treating the infection first is the obvious choice before initiating biologics. Apart from this, we order for HIV, hepatitis B surface antigen, and HCV for viral profile status before starting any biologics. If latent hepatitis is found, then we refer to a hepatologist for entire viral load status, liver function test, etc., for getting a clearance of the infection threshold. Few clinical published data exist with secukinumab regarding usage in latent hepatitis patients along with antiviral prophylaxis without any reactivation.

Dr. Sushil Pande

Most of the immunosuppressive agents used for the treatment of psoriasis have important safety concerns as they inhibit T-lymphocytes playing an important role in the causation of psoriasis. Being cytotoxic drugs, they require intense monitoring. Similarly, biologics such as etanercept, infliximab, and adalimumab inhibit tumor necrosis factor-alpha (TNF-alpha) which is the important cytokine release by T-cell-activated macrophages. TNF-alpha is responsible for protective cell-mediated immunity against intracellular pathogens such as Mycobacterium tuberculosis or viruses. Considering the risk of reactivation of TB in a country like India where there is a high incidence of subclinical exposure to M. tuberculosis, the use of TNF-alpha antagonists requires intense screening for TB by doing chest X-ray, Mantoux test, etc. However, secukinumab being IL-17 inhibitor may also inhibit TNF-alpha; hence, screening for TB is suggested by some experts. Pooled data of safety from five randomized controlled Phase 3 studies showed no reactivation of TB after 1 year of therapy. Furthermore, secukinumab treatment was comparable to control with regard to lack of effect on M. tuberculosis dormancy.[3] In clinical practice, I have not encountered a patient with reactivation of TB. IL-17 cytokine is said to be important in protection against extracellular organisms and Candida species. Preexisting infection with extracellular organisms mostly by pathogenic bacteria and some viruses in the blood or tissue fluids and Candida infection needs to be ruled out prior to initiation of secukinumab therapy as per data obtained in clinical studies.[4] However, in real-life clinical experience, chances of Candida infection were found to be minimal. The following monitoring is suggested for secukinumab therapy.

  • CBC with differential before treatment, after 4 weeks, 12 weeks, and then, every 3 months
  • Alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase before treatment, after 4 weeks, 12 weeks, and then, every 3 months
  • Hepatitis B serology before treatment
  • HIV and hepatitis C serology before treatment as indicated by patient history, clinical signs, or other laboratory test results
  • Urine pregnancy test.



  For How Long Have You Have Prescribed Secukinumab? Top


Dr. Manas Chatterjee

I have been using secukinumab since the time it has been marketed in India. In an individual patient, I have used it for a maximum period of 3 years and ongoing. However, in long-duration cases, I reduce the frequency of the drug progressively.

Dr. Sushil Pande

We have administered secukinumab therapy for a duration of >1 year in the recommended schedule without any side effects.


  Does Secukinumab Show Lack of Efficacy After Prolonged Use? What are Chances of Formation of Neutralizing Antibodies? Top


Dr. Manas Chatterjee

As per the clinical data and plethora of reports, the chances of antidrug antibody (ADA) formation with secukinumab are <1% in 5 years of follow-up.[5] However, lack of efficacy is not just attributed to ADA formation and a plethora of factors such as higher expression of other pathways of TNF, CXCL, IL-22, IL-17F, IL-36, etc., might also be responsible. I call it “life finds a way.” When you block one inflammatory pathway, other pathways get activated to continue the process. In these situations of biologic fatigue, it is best to change the drug if the improvement dips below PASI 50 with standard dosage. First, increase frequency of administration and then dose can be increased. if this does not work, then the drug can be changed.

Dr. Sushil Pande

Secukinumab has minimal chances of ADA formation responsible for drug neutralization or hypersensitivity reactions. The current study published in European Journal of Dermatology Venereology has documented this finding.[5] In general, when ADA is formed, the drug is neutralized leading to lack of efficacy on continued use. Biologicals such as etanercept, adalimumab, and secukinumab are expensive molecules. When ADA is formed, such expensive molecules become less effective or not effective at all despite its sustained use. In country like India, this could be a real problem for patients with regard to affordability. Chances of ADA are maximum with etanercept or adalimumab; thus, they need to be combined with conventional antipsoriatic systemic immunosuppressives such as methotrexate, azathioprine, or cyclosporine to decrease the chances of ADA formation or to compensate for biological failure. There is no need of combination therapies with secukinumab, like combining it with methotrexate.

Secukinumab has the fastest onset of action as compared to other biological such as etanercept or adalimumab. It has a faster onset of action than immunomodulator drug like cyclosporine. Drugs such as methotrexate or azathioprine or NB UVB therapy take more time to show its efficacy in chronic plaque psoriasis.


  How is Secukinumab Available and How it is Administered? Top


Dr. Manas Chatterjee

It is available as 150 mg lyophilized powder vial and needs to be reconstituted and administered as per manufacturer's guidelines.

Dr. Sushil Pande

Secukinumab is available in India is the form of a vial containing 150 mg of lyophilized powder that need to be dissolved with 1 ml of distilled water to make uniform or homogenous suspension. This is injected subcutaneously mostly in the abdomen wall or anterolateral thigh. However, this is not available as a prefilled syringe unlike etanercept or adalimumab which has the ease of self-administration.


  What About Use of Secukinumab in Pregnancy and Lactation? Top


Dr. Manas Chatterjee

Secukinumab is a pregnancy B category drug as per animal study reports of no teratogenicity. However, human studies are lacking with secukinumab in pregnancy; thus, it is better to avoid. Moreover, studies are also lacking upon secukinumab's excretion in human breast milk. Recent AAD guideline suggests that men attempting conception with their partner may use secukinumab. Only biologic that is approved till date in pregnancy is Certolizumab which has been approved by the Food and Drug Administration for usage in pregnancy, as it does not cross the placenta.[6]

Dr. Sushil Pande

Secukinumab along with other biologics such as etanercept and adalimumab are labeled as a pregnancy category B drug. Hence, it can be given in pregnancy; however, as mentioned above, as most of the data till date about secukinumab use are coming from clinical trials where pregnant and lactating women population is excluded, one cannot be very sure of its safety in pregnancy. Despite the fact that risk of transplacental transfer of immunoglobulin G antibody like secukinumab is maximally in the third trimester, in our opinion, it is better to be avoided in pregnant or lactating mothers unless benefits overweigh the risk involved.[6]


  Can it Be Used in Children? Top


Dr. Manas Chatterjee

Recent AAD guidelines have not considered secukinumab for pediatric psoriasis due to lack of evidence, and trials are going on in pediatric psoriasis patients for establishing safety and efficacy.

Dr. Sushil Pande

It is suggested to be avoided in pediatric population.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Koenders MI, van den Berg WB. Secukinumab for rheumatology: Development and its potential place in therapy. Drug Des Devel Ther 2016;10:2069-80.  Back to cited text no. 1
    
2.
Tiberio R, Graziola F, Miglino B, Veronese F, Annali G, Savoia P. Secukinumab for psoriasis in obese patients: Minireview and clinical experience. Case Rep Dermatol 2019;11:29-36.  Back to cited text no. 2
    
3.
Kammüller M, Tsai TF, Griffiths CE, Kapoor N, Kolattukudy PE, Brees D, et al. Inhibition of IL-17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections. Clin Transl Immunology 2017;6:e152.  Back to cited text no. 3
    
4.
Armstrong AW, Papp K, Kircik L. Secukinumab: Review of clinical evidence from the pivotal studies ERASURE, FIXTURE, and CLEAR. J Clin Aesthet Dermatol 2016;9:S7-12.  Back to cited text no. 4
    
5.
Reich K, Blauvelt A, Armstrong A, Langley RG, de Vera A, Kolbinger F, et al. Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits low immunogenicity in psoriasis patients treated up to 5 years. J Eur Acad Dermatol Venereol 2019;33:1733-41.  Back to cited text no. 5
    
6.
Porter ML, Lockwood SJ, Kimball AB. Update on biologic safety for patients with psoriasis during pregnancy. Int J Womens Dermatol 2017;3:21-5.  Back to cited text no. 6
    




 

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