|Year : 2021 | Volume
| Issue : 5 | Page : 674-682
Systemic management of psoriasis patients in Indian scenario: An expert consensus
Murlidhar Rajagopalan1, Manas Chatterjee2, Abhishek De3, Sunil Dogra4, Satyaki Ganguly5, Bikash Ranjan Kar6, Nina Madnani6, Shekhar Neema7, SG Parasramani8, Krina Patel9, Sushil Tahiliani10
1 Department of Dermatology, Apollo Hospitals, Chennai, Tamil Nadu, India
2 Department of Dermatology, Command Hospital, Kolkata, West Bengal, India
3 Department of Dermatology, Calcutta National Medical College, Kolkata, West Bengal, India
4 Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Raipur, Chhattisgarh, India
5 Department of Dermatology, Institute of Medical Sciences and Sum Hospital, Siksha ‘O’ Anusandhan, Bhubaneshwar, Odisha, India
6 Visiting Dermatology Consultant, P. D. Hinduja National Hospital and Medical Research Centre, Mumbai, Maharashtra, India
7 Department of Dermatology, Armed Forces Medical College, Pune, Maharashtra, India
8 Department of Dermacosmetology, Lilavati Hospital, Mumbai, Maharashtra, India
9 Department of Dermatology, Gujarat Medical Education and Research Society Medical College, Sola, Gujarat, India
10 Consultant Skin and S.T.D. Specialist, Dermatosurgeon, Dr. Tahiliani's Clinic, Bandra West, Mumbai, Maharashtra, India
|Date of Submission||11-Feb-2021|
|Date of Decision||07-Jul-2021|
|Date of Acceptance||19-Aug-2021|
|Date of Web Publication||10-Sep-2021|
Senior Consultant, Department of Dermatology, Apollo Hospital, Chennai, Tamil Nadu
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Psoriasis is a common inflammatory disease with significant comorbidities, and regardless of its extent, it affects the patients' quality of life. The various modalities of treating psoriasis comprise topical or systemic medications, phototherapy, and an array of biologic agents. There is a lack of Indian recommendations on the management of psoriasis with these different modalities and challenges faced by the clinicians in day-to-day practice. Aim: To develop India-specific consensus for systemic management of patients with moderate-to-severe psoriasis. Method and Results: A panel of dermatology experts, based on the evidence and international recommendations, coupled with their own clinical experience, developed recommendations for systemic management of patients with moderate-to-severe psoriasis. Conclusion: These recommendations are meant to provide guidance in terms of choice of systemic therapies, dosing, effectiveness, and safety. It also addresses clinical challenges that may be experienced during psoriasis management.
Keywords: Biologics, conventional, Indian consensus, psoriasis, systemic
|How to cite this article:|
Rajagopalan M, Chatterjee M, De A, Dogra S, Ganguly S, Kar BR, Madnani N, Neema S, Parasramani S G, Patel K, Tahiliani S. Systemic management of psoriasis patients in Indian scenario: An expert consensus. Indian Dermatol Online J 2021;12:674-82
|How to cite this URL:|
Rajagopalan M, Chatterjee M, De A, Dogra S, Ganguly S, Kar BR, Madnani N, Neema S, Parasramani S G, Patel K, Tahiliani S. Systemic management of psoriasis patients in Indian scenario: An expert consensus. Indian Dermatol Online J [serial online] 2021 [cited 2021 Sep 25];12:674-82. Available from: https://www.idoj.in/text.asp?2021/12/5/674/325854
| Introduction|| |
Psoriasis is a common inflammatory disease affecting approximately 2–3% of the world population. In India, the prevalence of psoriasis in adults varies from 0.44 to 2.8%. It is twice more common in males compared to females, and most of the patients are in their third or fourth decade at the time of presentation.
The exact understanding of the etiopathogenesis of this remains unclear. The current consensus is that psoriasis is a predominantly T-cell-mediated disorder, genetically determined, and influenced by environmental factors.
Beyond the physical dimensions of the disease, psoriasis has an extensive emotional and psychosocial effect on the patients, which makes appropriate management mandatory. However, with the added complexities of frequent relapses, nonresponse to conventional treatment, and involvement of difficult-to-treat areas such as palms, soles, and nails, it becomes difficult. The wider range of available treatment options results in a paradox of plenty.
The various modalities of treating psoriasis comprise phototherapy, topical or systemic medications, and an array of biologic agents.
Topical therapies (such as corticosteroids, vitamin D analogs) and phototherapy are common first-line treatments. These therapies have limitations due to the lack of long-term efficacy and safety data. Further compliance can be an issue with certain modalities like phototherapy (only 11% of the patients receive the recommended regimen of at least three sessions weekly). In India, access to phototherapy is a major limiting factor due to the financial burden and time constraints for traveling.
Systemic treatments such as methotrexate (MTX), cyclosporine, acitretin, and small molecules, like apremilast, are widely used in routine clinical practice worldwide., Despite their availability and cost-effectiveness, only 0.5–22.6% of the patients are prescribed oral systemic therapies. The main reasons reported in this survey for physicians not initiating or maintaining treatment were related to concerns about the long-term safety or tolerability and efficacy of the currently available oral systemic therapies. One of the reasons for the under-prescription could be the lack of specific guidelines or recommendations addressing such real-life clinical practice challenges.
Biologics, though useful, are not widely accepted among Indian patients considering their high costs and lack of long-term safety data in the Indian patients for most drugs. Their usage also requires careful screening of eligible patients and continuous monitoring during treatment., Counselling a patient, before the initiation of a biologic, is an integral part of management.
The recently published (2019) American Academy of Dermatology (AAD) and the National Psoriasis Foundation (NPF) recommendations highlight the key considerations regarding biologics usage. However, there is a need for country-specific recommendations. Challenges like tuberculosis infection/potential reactivation, therapy cessation, suboptimal dosing due to affordability are specific to India. There is also a lack of Indian recommendations among dermatologists on how and when to transit from one treatment to another in routine clinical practice. Furthermore, there are some challenges with biologics as well. There are some patients who do not respond to certain biologics (primary inefficacy), whereas others who respond initially lose response over time (secondary inefficacy), and the patients who respond but do not reach the desired magnitude of response (partial response).
To address this existing caveat in clinical practice, a group of Indian dermatologists created an India-specific consensus for systemic management of patients with moderate-to-severe psoriasis.
| Methodology|| |
An advisory board meeting was organized with a steering committee of the top 10 dermatologists across India. The consensus was obtained on therapeutic approaches and current treatment challenges with respect to the following topics based on the current evidence, guidelines, and their clinical experience [Figure. 1]:
- Conventional systemic agents: The systemic agents discussed were the ones most commonly used in India, viz. methotrexate (MTX), cyclosporine (CsA), acitretin, and apremilast.
- Biologics: The biologics discussed were the ones currently available in India, viz. etanercept, infliximab, adalimumab (biosimilar), and secukinumab.
- Clinical challenges with biologics: The recommendations were focused primarily on the loss of efficacy and transition among the biologics.
Expert consensus recommendation
Therapeutic approaches and current treatment challenges with conventional systemic therapies
Conventional systemic therapy continues to find use in the majority of psoriasis patients in India because of the ease of administration, low cost, and vast experience of their use.
The final Indian expert consensus recommendations for the appropriate and safe use of conventional drugs are enumerated in [Table 1] with some additional points highlighted here.
|Table 1: Expert consensus recommendations for conventional agents,,,,,,,,,,,,,,,,,|
Click here to view
Expert consensus recommendations for MTX
Since its approval in 1972 by the US Food and Drug Administration (FDA), MTX remains a gold standard for the management of psoriasis.,,
Recommendations to monitor for hepatotoxicity were individualized to the current Indian practices. It was highlighted that the onset of efficacy is delayed (may take up to 16 weeks to achieve Δ PASI 75) so in the patients who need early onset of action, another drug should be chosen. There was a difference of opinion regarding the relapse and remission with MTX. Post-drug discontinuation, some doctors have experienced relapse immediately, whereas some have not.
Expert consensus recommendations for CsA
CsA is a calcineurin inhibitor indicated for the short-course treatment of moderate-to-severe psoriasis. It offers a rapid and significant resolution of the disease, sustained remission, and a positive impact on the quality of life (QoL), making it an ideal choice in a crisis.
However, the treatment effect is short-lived and exacerbation occurs soon after the treatment discontinuation. Methotrexate and acitretin are recommended as sequential treatments after the initial flare is controlled by CsA with an overlap of 1 month to avoid relpase due to discontinuation of CsA. As per the international recommendations, combining cyclosporine with phototherapy is contraindicated. However, the Indian experts recommended the concomitant use of psoralen (P) and ultraviolet (UVA) (PUVA) as well as narrow-band ultraviolet B (NBUVB) with cyclosporine in Indian patients, especially in recalcitrant situations where the options are limited. This is because the risk of combining the drugs has not been documented in type IV or V skin. As a matter of precaution, this combination is better avoided.
The expert guidance on the use of CsA in children was similar to the available literature evidence.,,,,
Acitretin: Guidance on the appropriate use in the management of psoriasis
Acitretin is a second-generation synthetic retinoid that was first synthesized 35 years ago and was first introduced 25 years ago in Spain. It holds a unique role in the management of psoriasis because of its different modes of action.
The efficacy of acitretin is dose-dependent, and the response varies from patient to patient.
Caution is recommended on the concomitant use of methotrexate and acitretin, as sporadic severe hepatotoxic reports have been reported. Similarly, a combination of CsA and acitretin is not recommended as this may lead to CsA toxicity. Teratogenicity is a serious concern with acitretin, and adequate monitoring is required, especially in the higher-risk groups.,,,,,,
Apremilast: Guidance on the appropriate use in the management of psoriasis
Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, approved by the US FDA in 2014, is the first oral drug to receive FDA approval for psoriasis since 1996. Although its exact mechanism of action in psoriasis is unclear, it has shown efficacy in moderate-to-severe plaque psoriasis. The Indian expert consensus was in line with the international literature and guidelines (European S3 Guidelines).,, The experts agreed that it works well in mild to moderate psoriasis rather than severe psoriasis. It also improves psoriasis at difficult sites such as palmoplantar, nail, and scalp. They also recommended regular weight monitoring in the patients on apremilast. Depression is mentioned in the summary of product characteristics (SmPC) as a potential side effect, with apremilast, however, the experts were of the opinion that depression is more often reported in patients with predisposing factors. The drug does not seem to be a good choice for arthropathy.
Practical challenges with conventional systemics
Clinicians are always in a dilemma about the duration of therapy, due to concerns of toxicity with conventional systemics. The consensus was that the therapy should not be stopped, considering the chronic nature of the disease. Nonetheless, due to safety concerns, the duration of treatment needs to be individualized. The board agreed that the patients can be continued on treatment with strict monitoring protocols or can be considered for discontinuation or tailoring of therapy if sustained remission has been maintained for 6 months.
The criteria for the re-initiation of therapy as suggested by the experts:
- The Dermatology Life Quality Index (DLQI)>5
- Physician Global Assessment (PGA)>2
- The body surface area (BSA)>10
- Psoriasis Area and Severity Index (PASI)>5.
| Therapeutic Approaches and Current Treatment Challenges with Biologics|| |
Over the past few years, newer and even more effective biologic therapies with more targeted mechanisms of action have become available to the patients.
Biologics targeting tumour necrosis factor (TNF-α) were developed first and are often referred to as the first-generation biologics: etanercept, infliximab, and adalimumab. They are indicated in patients with chronic moderate-to-severe psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate.,,
Second-generation biologics emerged from 2009 with antibodies targeting the IL-23/Th17-pathway: ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, and tildrakizumab.
Secukinumab is the only second-generation biologic available in India at present. It is indicated as the first-line systemic in moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.,
Eligibility criteria for biologics in psoriasis
Indian dermatologists concurred that biologics are generally administered as per the international guideline recommendations and literature evidence (AAD 2008, AAD 2019, BAD 2017, European S3,) and protocol.,,,,, Additionally, in line with the international recommendations, biologics are the first-line therapy in patients with a limited disease where there is significant impairment of quality of life. In such scenarios, secukinumab is the preferred biologic, considering the safety and its approval as the first-line systemic indication in patients with moderate-to-severe psoriasis [Figure 2].
Guidance on the appropriate use of biologics
The recommendations on biologics were limited to etanercept, adalimumab, infliximab, and secukinumab on the basis of their availability in the Indian market and aligned to the international recommendations [Table 2]. The screening and monitoring on the overall biologics were similar across both classes due to TB concerns in India, although the risk is less with the interleukin-17 inhibitor.
Considering that India is a self-pay market, India-specific changes/adaptations have been recommended with regards to the dose and duration of therapy. Conversely, the final consensus stated that for optimal benefits, dosing should be as per the drug label.
The proposed ranking of biologics (available in India) in terms of efficacy was as follows:
Clinical challenges with biologics
There is limited evidence on the practical challenges faced with biologics. There is inconsistent data on the criteria to determine the primary failure and secondary failure and the management of psoriasis in such scenarios. The experts agreed that the secondary failure should be when there is
- Loss of PASI 50 response
- DLQI score >5
- Absolute PASI >5
- BSA >10.
In case of secondary failure, one should follow the algorithm as shown in [Figure 3] to rule out the other causes.,,, The expert recommendations on the above-mentioned issues were based on their clinical experience and literature review [Table 3].
|Figure 3: Expert Consensus Recommendations on Addressing Reduction of Efficacy|
Click here to view
| Conclusion|| |
The management of psoriasis has evolved in the last decade with a newer class of biologics marking a watershed in the management of psoriasis. The PASI 90 response is now considered as treatment success instead of PASI 75. Due to the differences in the global health care markets as compared to India, the application of global guidelines to India has been challenging. Thus, there has been a requirement for India-specific recommendations based on the integration of evidence and clinical experience.
It was, therefore, the aim of this expert panel to address issues such as choice of therapy, dosing, effectiveness, and safety. for systemics, biologics. It also addressed the clinical challenges faced with these in the ongoing management of psoriasis with these drugs.
The experts contemplated on each of these points by reviewing the published scientific evidence, guideline recommendations, and combined it with their real-world clinical experience for a structured and individualized approach to the treatment.
Financial support and sponsorship
The advisory board meeting for the formulations of this expert consensus was organized by the Novartis HealthCare Pvt Ltd. However, Novartis has played no role in the decision-making.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]