2023 guidelines on the management of psoriasis by the Dermatological Society of Singapore

ABSTRACT

Introduction: Psoriasis is a multisystem, chronic, inflammatory dermatological disease. In routine clinical practice, the management of psoriasis varies significantly. The current study aimed to develop a set of practice guidelines relevant to dermatology practice in Singapore.

Method: The Psoriasis Therapeutic Guidelines Workgroup, comprising members of the Dermatological Society of Singapore with a subspecialisation in psoriasis, was convened to develop the guidelines. Clinical questions on selected topics were generated and refined by the workgroup. A literature search using PubMed was performed on their assigned topics from June 2013 to December 2023. The articles were included and graded based on the level of evidence.

Results: The guidelines address topics ranging from clinical assessment to practical considerations in the management of mild, moderate and severe psoriasis, including delivery of care, referrals to specialists and adherence to treatment. The recommended therapies include phototherapy, methotrexate, acitretin, cyclosporine; apremilast; topical corticosteroids, calcipotriol, topical calcineurin inhibitors; and biologics (i.e. adalimumab, infliximab, secukinumab, ixekizumab, ustekinumab, etanercept) either in combination or as monotherapy. Common therapeutic concerns relating to biologic use were addressed. Recommendations on generalised pustular psoriasis, palmoplantar pustular psoriasis and psoriatic arthritis were also made. Patients on systemic therapy would receive appropriate vaccine counselling. Therapeutic implications in special populations, such as pregnant/lactating women, children, the elderly, those undergoing surgery and those suffering from specific infections and cancer were addressed.

Conclusion: These guidelines were developed for dermatologists, family physicians, rheumatologists and other specialists to support their selection of appropriate management options.

CLINICAL IMPACT

What is New

• The Dermatological Society of Singapore has developed guidelines for the management of psoriasis, which is currently managed in diverse ways.
• The guidelines cover aspects of clinical assessment and treatment across severity levels.

Clinical Implications

• The guidelines emphasise the management of pustular and palmoplantar psoriasis, psoriatic arthritis and psoriasis in special populations.
• It also provides a comprehensive framework for dermatologists and promotes standardised patient care.
• Furthermore, the guidelines discuss the indications and selection of biologic therapy in the management of psoriasis.

Psoriasis is a chronic multisystem, autoimmune and inflammatory dermatological condition. It usually persists throughout one’s lifetime, and spontaneous remission is rarely seen. As per the World Health Organization (WHO), the global prevalence of psoriasis is about 0.09%–11.4%.¹

Psoriasis may be linked to other serious diseases, such as depression, psoriatic arthritis (PsA), diabetes and heart disease. PsA is a common comorbidity occurring concurrently with psoriasis. According to WHO, the global prevalence of PsA is about 1.3%–34.7%.¹ The treatment of psoriasis should address both psychosocial and clinical manifestations of the disease. Several innovative therapies are available for psoriasis, ranging from topical treatment to oral systemic therapy and novel biologic treatments. The treatment regimen is chosen based on the extent of the disease, relevant comorbidities and the effect of the disease on patients’ quality of life.

The primary goal of this study is to provide evidence-based guidelines for managing different types of psoriasis, with a focus on plaque psoriasis.

Target group

These guidelines have been developed for dermatologists, family physicians, rheumatologists and other specialists to enhance their understanding of psoriasis and support their decision-making in selecting the most appropriate management option. With the advent of new biologics, these guidelines will also help dermatologists decide on the appropriate indication and selection of biologic therapy. The guidelines are not meant to be a didactic algorithm for the treatment of psoriasis. They should be individualised for each patient and used in conjunction with the personal experience of the prescribing physician.

METHOD

The Psoriasis Therapeutic Guidelines Workgroup comprises 12 dermatologists from the Dermatological Society of Singapore (DSS). They subspecialise in psoriasis and accepted the invitation of the DSS Executive Committee to participate in this workgroup. The aim was to develop a set of practice guidelines for clinicians in Asia, particularly in Singapore, in an easy-to-read format while incorporating more recent literature.

Clinical questions on selected topics were created and refined by the workgroup based on clinical experience as well as feedback on the main concerns of patients with psoriasis and members of the Psoriasis Association of Singapore. A literature search using PubMed was performed by the workgroup members on their assigned topics. Journal articles published from June 2013 to December 2019 were included and graded based on the level of evidence. Subsequently, key articles and references up to December 2023 were reviewed,^2-14 including changes in biologics on the subsidised drug list of the Ministry of Health, Singapore.¹⁵

These guidelines were based on the first edition of the DSS Psoriasis Management Guidelines, published on 30 June 2016. Therapeutic guidelines existing worldwide, especially the joint American Academy of Dermatology (AAD)-National Psoriasis Foundation (NPF) 2019 guidelines for the management of psoriasis along with an emphasis on awareness and attention to comorbidities; the 2019 joint AAD-NPF guidelines of care in managing psoriasis with biologics; the joint American College of Rheumatology-NPF 2018 guidelines for the management of PsA;¹⁶ the 2017 National Institute for Health and Care Excellence guidelines for the management of psoriasis;¹⁷ the 2009 Canadian guidelines and 2016 Addendum to the Canadian guidelines; the 2017 British Association of Dermatologists guidelines; and the 2017 European S3-Guideline on the systemic treatment of psoriasis vulgaris, were used as references for developing the current guidelines. References were also made to the regional psoriasis therapeutic guidelines and the National Skin Centre psoriasis guidelines in Singapore.

The draft guidelines and evidence were reviewed in a series of workgroup meetings. Consensus was obtained, defined as a minimum of 90% agreement, on guidelines that lacked sufficient evidence from the literature.

Guidelines reflect considerations of benefits and harms, side effects and risks. Social values, psychological aspects and preferences were identified in consultation with patients in public and private healthcare clinics, as well as with members of patient support group, the Psoriasis Association of Singapore.

Expert panel members were invited from different public and private healthcare institutions to ensure a balance of views, equity, feasibility and acceptability. The experts were dermatologists with subspecialisation in psoriasis and special expertise in cutaneous infections and photodermatology. In addition, a rheumatologist, YY Leung, provided input for drafting the section on PsA.

While formulating the guidelines, the experts also considered the costs of biologics and the availability of medication assistance funds. However, they recognised that not all patients would be eligible for funding, and some would seek care as private patients.

The modified Delphi method was used for formulating the guidelines. The workgroup adopted the Scottish Intercollegiate Guidelines Network grading system for the grade of recommendations and level of evidence, presented in Supplementary Table S1.¹⁸ Two key opinion leaders in the field of psoriasis reviewed the guidelines critically. The document was vetted and approved by the entire panel of authors. Statements were accepted when a unanimous agreement was reached. The entire process was completed in 3 rounds. Printed copies of the guidelines were distributed to the members of the DSS.

The guidelines will be updated 5 years after publication. A description of the method followed to develop the guidelines is provided in Supplementary Fig. S1. The guidelines are presented in Supplementary Tables S2 and S3.^19-30

RESULTS

In addition to addressing the clinical assessment and management of various severities of psoriasis, the guidelines provide detailed recommendations for handling specific subtypes, such as pustular and palmoplantar psoriasis. The scope also includes subgroups of PsA, ensuring comprehensive coverage of the disease spectrum. Moreover, the guidelines offer insights into managing psoriasis in special populations, such as children, pregnant women and individuals with malignancies, recognising the unique challenges and considerations these groups may face in treatment and care. Overall, these guidelines offer a thorough framework for healthcare providers to deliver effective and tailored management strategies for individuals with psoriasis across different manifestations and circumstances.

DISCUSSION

Psoriasis encompasses various subtypes, each presenting distinct clinical features and treatment considerations. Additionally, managing psoriasis requires attention to comorbidities, such as hepatitis, tuberculosis (TB), human immunodeficiency virus (HIV) and malignancies, which may influence treatment decisions and overall disease outcomes. Special considerations, such as pregnancy and adherence management, further highlight the complexity of psoriasis care and the need for tailored approaches to ensure optimal outcomes for patients.

Management of moderate and severe psoriasis

Phototherapy

Phototherapy is the recommended second-line therapy for patients with psoriasis involving >10% of the body surface area (BSA). Both ultraviolet B (UVB) and psoralen + UVA are effective in clearing psoriasis when delivered 2 to 3 times a week in the clearance phase until minimal residual activity. The treatment is then reduced to once weekly or fortnightly during the maintenance phase before cessation.

Conventional systemic therapy

About 20% of patients with psoriasis experience moderate-to-severe symptoms and are considered suitable for systemic therapy.³¹ Severe disease is defined as Psoriasis Area and Severity Index (PASI) ≥10, BSA ≥10% or Dermatology Life Quality Index (DLQI) ≥10 (the rule of 10s). The disease in high-impact areas is associated with significant psychological or functional disability (e.g. major parts of the scalp, genitals, palms, soles and intertriginous areas). A summary of recommendations for managing moderate-to-severe psoriasis using phototherapy and systemic therapy is presented in Table 1.^31,32

Table 1. Summary of recommendations for the management of moderate-to-severe psoriasis: phototherapy and systemic therapy.^31,32

Biologics and their use in special situations

Biologics are employed as either standalone treatments or in conjunction with other systemic or topical medications for psoriasis management.³¹ A summary of recommendations for the management of moderate-to-severe psoriasis using biologics and in special situations is provided in Table 2.^5,31-35

Table 2. Summary of recommendations for biologics in the management of moderate-to-severe psoriasis and in special situations.^5,31-35

Management of pustular psoriasis

Pustular psoriasis, a rare, systemic, immune-mediated dermatological disorder, affects both children and adults. It is classified into generalised and localised pustular psoriasis depending on whether the pustules are widespread or localised. A summary of treatment recommendations for generalised pustular psoriasis and palmoplantar pustular psoriasis is presented in Table 3. Moreover, a multicentre study involving Asian patients revealed that intravenous spesolimab enhanced outcomes while managing flares of generalised pustular psoriasis.⁴

Table 3. Summary of treatment recommendations for generalised pustular psoriasis, palmoplantar pustular psoriasis and impetigo herpetiformis.

Practical considerations in psoriasis

Delivery of care and social and psychological aspects of psoriasis

Psoriasis is associated with several comorbidities, and PsA has arguably the most well-known association with psoriasis. Other comorbidities are also associated with psoriasis, such as cardiovascular disease (CVD) and metabolic syndrome (MetS) and its components, including obesity, hypertension, diabetes mellitus and dyslipidaemia.

Indications for referral to specialists

A patient should be referred to a dermatologist when: (1) the patient presents with a complex disease, i.e. an extensive disease that is likely to require systemic treatment, with BSA >10%; (2) the disease is associated with significant psychological distress, e.g. DLQI >5 or less than a 5-point reduction compared with baseline after treatment; (3) the patient is unsatisfied with the current level of control; (4) the patient exhibits suboptimal response to primary care management, i.e. less than 75% reduction in BSA involvement or PASI; or (5) the patient develops significant adverse effects to topical medications, e.g. skin atrophy, striae, hirsutism and steroid-induced acne. Referral to a dermatologist might also address the need for urgent in-patient care—when the patient presents with generalised pustular psoriasis, erythrodermic psoriasis or acute unstable psoriasis.³⁶

Addressing poor adherence to treatment

The presence and extent of adherence should be routinely monitored by questioning the patients directly. The top 3 causes of poor adherence to topical agents for psoriasis management are low efficacy, time consumption and inadequate cosmetic characteristics.³⁷ Some of the strategies to improve adherence are listed below.

Patients should be provided with information about psoriasis, such as through patient information leaflets or websites, including resources like the Psoriasis Association of Singapore (http://www.psoriasis.org.sg/), DSS (https://www.dermatology.org.sg/education/ psoriasis/) and NPF (https://www.psoriasis.org/). The social impact of psoriasis should be recognised, which may include addressing emotional and psychological aspects alongside physical symptoms. Patients should be informed about the potential side effects of topical therapies. Frequent and regular follow-up visits are highly recommended, especially in the initial stage of treatment, to monitor progress, adjust the treatment plan as needed and address any concerns or issues that may arise.³⁸

Considerations in PsA

PsA, affecting approximately 20% of those with psoriasis, is a chronic inflammatory condition marked by substantial morbidity and a notable impact on quality of life.² Screening tools and diagnostic approaches are crucial in the effective management of PsA, facilitating early identification and appropriate referral to rheumatologists.

Screening tools

Screening tools for PsA have been developed to help dermatologists identify patients for referral to rheumatologists. The Psoriasis Epidemiology Screening Tool (PEST)³⁹ was chosen, as it can be completed rapidly by patients and has good sensitivity.

Diagnosis

There is a lack of serum biomarkers and specific laboratory tests for PsA. Erythrocyte sedimentation rate, fibrinogen levels and C-reactive protein may not always be increased, even in individuals with active disease.⁴⁰ Rheumatoid factor and anti-cyclic citrullinated peptide antibodies are absent in about 95% of patients with PsA. If present, it is desirable to use clinical features and imaging features for differentiating PsA from rheumatoid arthritis.⁴¹ Human leukocyte antigen (HLA)-B*27 can identify patients with psoriasis more prone to develop PsA or for the early diagnosis of PsA when inflammatory back pain is present.⁴²

Imaging features

Destruction of cartilage and bone along with new pathological bone formation is the hallmark of PsA on a radiograph.⁴¹ This simultaneous joint destruction and formation is unique to PsA.

• Spondylitis and sacroiliitis in PsA can mimic ankylosing spondylitis (AS). However, the development of non-marginal syndesmophytes, unilateral sacroiliitis and asymmetry of syndesmophytes may distinguish PsA from AS.
• Ultrasonography may be performed to check for enthesitis.
• Magnetic resonance imaging may provide information on bone marrow edema in axial and peripheral structures, such as entheses, synovitis and focal erosions.

Referral to a rheumatologist

Early identification and treatment of PsA can prevent irreversible joint damage. As primary care providers for patients with psoriasis, dermatologists play a pivotal role in providing holistic treatment and, where appropriate, organising multidisciplinary care.

The following clinical features may predict more severe disease outcomes in PsA, and co-management with a rheumatologist may be considered:⁴³ female sex, older age at diagnosis, obesity, smoking history, longer disease duration, higher baseline disease activity (≥5 affected joints and/or elevated inflammatory markers), presence of dactylitis or nail involvement, and worse baseline physical function.

The treatment for PsA encompasses conventional step-up strategies, initially utilising topical therapies for psoriasis and conventional synthetic disease-modifying antirheumatic drugs for arthritis. However, it also includes accelerated treatment pathways, where biologic DMARDs or targeted synthetic DMARDs may be employed as first-line therapy, if accessible and deemed appropriate.²

A summary of recommendations for PsA screening, referral and management is presented in Table 4.^44-46

Table 4. Summary of recommendations for psoriatic arthritis screening, referral and management.^44-46

Psoriasis in special populations and comorbidities

Pregnant and lactating women

Topical medication is usually the preferred treatment for psoriasis in pregnant and lactating women. As medications pass through the placenta and are found in breast milk in varying concentrations, they should be used with caution. Common psoriasis treatments, the descriptions of their use in pregnancy and lactation, their effects on fertility, and their earlier United States Food and Drug Administration (USFDA) categories are elaborated in Supplementary Table S2.^19-30

 Adalimumab and certolizumab may be acceptable in pregnancy, with certolizumab being the preferred biologic and safe in lactation. They may be given after consideration of the risk–benefit ratio and should be individualised.³⁵ If TNF-alpha inhibitors or other biologic therapies (excluding certolizumab) are given after week 22 of pregnancy, live vaccines such as Bacillus Calmette-Guérin should be delayed till after the infant is more than 6 months of age.⁴⁷

Children

Psoriasis affects around 1% of children and most commonly occurs during adolescence. Chronic plaque psoriasis is the most observed presentation in children, with sites such as the scalp, elbows and knees or skinfolds (i.e. those behind the ears, armpits and groin) being the most affected. Children with psoriasis may present with comorbidities, such as obesity, MetS and PsA.⁴⁸ Factors that are taken into account when selecting suitable treatments for psoriasis in the paediatric population are the safety profile, dosing schedule and approval of the drug in the paediatric population.

Methotrexate (MTX), cyclosporine (CyA) and acitretin, although not USFDA-approved for paediatric psoriasis, can be considered for short-term and intermittent usage.

Combining biologics with topical corticosteroids, with or without a vitamin D analogue, is a safe option for treating moderate-to-severe plaque psoriasis in children.

Adalimumab has been approved by Singapore’s Health Sciences Authority (HSA). Children aged ≥4 years and weighing ≥30 kg are initially administered a dose of 40 mg at week 0, followed by a maintenance dose of 40 mg every 2 weeks. For children weighing between 15 kg and 30 kg, the initial dose is 20 mg at week 0, followed by a maintenance dose of 20 mg every 2 weeks.^9,48

Secukinumab has demonstrated high efficacy in alleviating skin symptoms and enhancing the health-related quality of life in paediatric patients (aged 6 to 17 years)³ with severe chronic plaque psoriasis while maintaining a favourable safety profile.⁴⁹ For plaque psoriasis treatment in paediatric patients aged 6 years and above, the subcutaneous administration of the drug dose based on weight is recommended. Injections should be given at weeks 0, 1, 2, 3 and 4, followed by every 4 weeks thereafter. Patients weighing less than 50 kg (when dosing) should receive a dose of 75 mg. Patients weighing 50 kg or more (when dosing) should receive a dose of 150 mg, which may be increased to 300 mg monthly.^49,50

Ixekizumab, which targets interleukin (IL)-17A selectively, can be used in paediatric patients (aged 6 to <18 years) with moderate-to-severe psoriasis.⁵¹ It shows a similar safety profile to that of adults. Patients weighing over 50 kg should receive a recommended dose of 160 mg (2 80 mg injections) at week 0, followed by a dose of 80 mg every 4 weeks. Patients weighing between 25 kg and 50 kg are recommended a dose of 80 mg at week 0, followed by a dose of 40 mg every 4 weeks.^51,52 Ustekinumab can be administered subcutaneously (60 kg: 0.75 mg/kg/dose; 60 kg to ≤100 kg: 45 mg; 100 kg: 90 mg) at weeks 0 and 4, and then every 12 weeks, in children aged 12 to 17 years for the treatment of psoriasis.^21,53,54  

Elderly

Comorbidities, such as hyperlipidaemia, hypertension and type 2 diabetes, are more common in elderly patients. Therefore, the utilisation of systemic therapies may be restricted in this population. Drug interactions can also occur between psoriasis drugs, and concomitant medications can precipitate or aggravate psoriasis.^55,56

The primary goals are to clinically control the disease with safe and tolerable treatment modalities, satisfy patients’ expectations and improve their quality of life. Topical corticosteroids and topical vitamin D analogues are first-line treatments for mild psoriasis under appropriate guidance.⁵⁵ Caution must be exercised with topical corticosteroids due to their known cutaneous side effects.⁵⁵

Narrow-band UVB, acitretin, MTX and biologics are advised as first-line treatment options in elderly patients with extensive psoriasis. Newer IL-23 and IL-17 therapies with higher efficacy are other promising options for the elderly.⁵⁶

Dermatological drugs mainly excreted by the kidneys (e.g. MTX) may be eliminated more slowly in the elderly. Therefore, it is desirable to consider a dose reduction. MTX is also hepatotoxic, and caution must be exercised while prescribing this drug in the elderly.⁵⁵ In case of extensive disease, CyA is preferred as a second-line systemic treatment.⁵⁵

Despite the availability of many effective systemic treatments for psoriasis, deciding the treatment approaches for specific populations with psoriasis, such as patients with TB, HIV, hepatitis, malignancies or surgical patients, can be challenging. These groups are typically not included in clinical trials, and very few up-to-date reviews on psoriasis management in these populations are available.

TB

Patients with psoriasis on treatment with immunosuppressant medications are at a high risk of activating latent TB infection (LTBI). However, acitretin is well-tolerated in patients with LTBI.¹⁰

The gap between the initiation of biologic therapy for psoriasis and the development of clinical signs of TB or the confirmation of TB diagnosis may range from 3 to 12 months.⁵⁷ If the screening result or TB status is unclear or LTBI is suspected, therapy with biologics should not be initiated without consultation with a relevant physician (e.g. physicians specialising in infectious or respiratory diseases). The 2 preferred regimens for the treatment of TB infection in adults are rifampicin daily for 4 months (4R), or isoniazid daily for either 6 or 9 months (6H/9H).⁵⁸ Treatment with a biologic may be initiated as early as possible, typically 1 month after initiating prophylaxis for TB. If there is a suspicion of TB reactivation that is justified or a new infection during biologic therapy, the interferon-gamma release assay and chest X-ray should be repeated.

Treatment with TNF-α inhibitors and ustekinumab can be considered in individuals with LTBI after appropriate TB prophylaxis.⁵⁹ The risk of TB reactivation in patients with psoriasis and LTBI remains less with the use of IL-17 or IL-23 inhibitors. Hence, in cases where concerns about TB reactivation arise, prioritising IL-17 or IL-23 inhibitors over TNF-α inhibitors is recommended.⁶

HIV infection

Fundamental therapy of HIV with antiviral medications, such as highly active antiretroviral therapy (HAART), may have additional beneficial effects on dermatological lesions, such as complete or nearly complete symptom clearance in up to 90% of patients with HIV-associated psoriasis. Immunocompetent HIV patients may be treated with nearly all the therapeutic agents that can be used in an HIV-negative psoriasis patient provided there are no adverse interactions with HAART, if any. Treatment options include topicals (Level 1+, A), phototherapy (Level 2+, B), retinoids (Level 3, B), MTX (Level 4, D), CyA (Level 4, D) and biologics (Level 3, B).

Hepatitis

Hepatitis B

Screening should be done for Hepatitis B surface antigen (HBsAg) before starting the treatment with MTX, CyA and biologics in patients with psoriasis; screening for anti-HB antibodies is recommended. Patients should not be managed with immunosuppressive therapies in the acute hepatitis stage. However, treatment with biologics may be considered in patients presenting with resolved or chronic hepatitis under close supervision and in consultation with a gastroenterologist.

Recommendations for HBsAg-positive patients with psoriasis

It is advisable to avoid administering biologics to patients who are positive for HBsAg. Topicals, phototherapy, acitretin and apremilast should be considered. The screening for hepatitis B and C is not required for the initiation of apremilast, but drug cost and access may be prohibitive. Considerations for starting oral agents and biologics should be in consultation with gastroenterology. Input is required for choice of drug due to individual risk of liver fibrosis (e.g. acitretin),⁶⁰ hepatitis B reactivation risk, comorbidities and initiation of prophylaxis if indicated.  Inactive HBV carriers (HbsAg-positive, HBcAb-positive, HBV DNA <2000 IU/mL, acceptable transaminases) may be started on biologics with lower risk of HBV reactivation under prophylactic anti-HBV therapy.⁶¹ Antiviral therapy is suggested to commence either at the same time or 1 to 2 weeks before biologics.⁷ Reactivation of the HBV typically manifests during immune reconstitution, necessitating the continuation of antiviral therapy for 6 to 12 months following the cessation of immunosuppression.⁶¹ Prophylaxis is recommended with close monitoring through laboratory tests, including assessments of liver function and HBV DNA viral load.

Among HBsAg-positive patients, acitretin, apremilast,⁶¹ IL-17 inhibitors and IL-23 inhibitors⁶⁰ are considered low-risk for HBV reactivation (<1%) but still require monitoring for viral reactivation with transaminases and HBV DNA.⁶¹ Higher potency TNF inhibitors (infliximab, adalimumab, certolizumab⁶²) are considered high risk for reactivation (>10% risk level); ustekinumab,⁶³ etanercept⁶² and cyclosporine⁶¹ are moderate risk (1%–10%). While the use of MTX and CyA is contraindicated or relatively contraindicated in most guidelines, acitretin may be used along with monitoring of LFTs.

Recommendations for anti-HBc-positive patients with psoriasis

Before initiating treatment with CyA and biologics in patients with past hepatitis B exposure (anti-HBc-positive, HBsAg-negative patients), screening for HBV DNA load is recommended. The risk of reactivation for anti-HBc-positive, HBsAg-negative and HBV DNA-negative patients is lower than for HBsAg-positive patients. Such patients treated with TNF-α inhibitors, ustekinumab and CyA are associated with a moderate risk of HBV reactivation and should be monitored with transaminases and HBV DNA. MTX, acitretin or apremilast are associated with a minimal risk of reactivation and thus do not necessitate anti-HBV therapy. Patients on biologics and cyclosporine should be offered gastroenterology review with the option of antiviral prophylaxis on a case-by-case basis.

Hepatitis C

About 80% of patients with acute hepatitis C may develop chronic hepatitis C infection, defined as detectable viral replication for at least 6 months.⁶⁰ Liver enzymes could be normal in around 50% of patients with chronic hepatitis C. Recommendations for the management of these patients include serology before the initiation of treatment with MTX, acitretin, CyA and biologics and consultation with a gastroenterologist. Oral direct-acting antivirals are safe and effective treatment against hepatitis C and have high rates of sustained virological response.⁶⁴ Apremilast and IL-17 inhibitors seem to have a favourable safety profile for psoriasis. However, data are scarce, including data on the safety of IL-23 inhibitors in patients with hepatitis. MTX should be avoided in patients with chronic hepatitis. CyA use in chronic hepatitis is not well established.^57,59

MetS (hypertension/hyperlipidaemia/diabetes mellitus/obesity)

Beyond dermatological symptoms, systemic inflammation observed in psoriatic patients contributes to the phenomenon known as the psoriatic march. This suggests that inflammatory processes extending from the skin to systemic levels in psoriatic patients may trigger immune-mediated changes, leading to significant comorbidities, such as metabolic disorders (including obesity, hypertension and dyslipidaemia) and CVDs.¹¹

The occurrence of MetS is potentially 3-fold higher among individuals with psoriasis than in the overall populace, potentially influencing the preferred treatment options for specific patients.⁸

Multiple studies have identified a strong association between psoriasis and CVD. The American Heart Association and the American College of Cardiology have classified psoriasis as a condition that enhances the risk of atherosclerotic CVD. Annual metabolic screening for blood glucose or glycated haemoglobin, lipid levels, blood pressure and obesity (body mass index and/or waist circumference) should be included as part of the dermatological follow-up for patients with psoriasis. In addition, patient education regarding the cardiovascular risks associated with psoriasis should be provided during their follow-up appointments. Patients with diagnosed metabolic disorders or smoking should be advised on risk factor modification and to attain treatment targets.⁸

Malignancy

As several systemic therapies indicated in psoriasis are associated with an elevated risk of de novo or reactivated malignancies, caution is needed while choosing a therapeutic option for patients with a history of solid tumours. The staging and type of cancer, the burden of psoriasis, and the risk of recurrence of melanoma skin cancer and non-melanoma skin cancer (NMSC) have been recently diagnosed. Phototherapy (UVB 308 nm, UVB 311 nm), topical therapy and/or therapy with acitretin are recommended.⁵⁷ Preventative effects are observed with acitretin on NMSC. Thus, they are preferred in patients with an elevated risk for skin cancers. If possible, it is desirable to avoid CyA and MTX in this kind of setting.⁶⁵ It is also advised to avoid biologics in patients with a recent or recurrence of malignancy unless the likelihood of cure is high (including adequately treated NMSC) and/or the malignancy was diagnosed and managed more than 5 years ago. If the malignancy is less than 5 years post-remission, biologics should be considered in consultation with an oncologist.

Surgery

The likely advantage of postoperative infection prevention by the discontinuation of psoriasis treatment needs to be balanced with the risk of a psoriatic flare (Level 4, Grade D, good practice points). In the case of minor surgeries, such as those involving skin or dental structures, any treatment that is systemic may be continued. Before major surgeries, it is desirable to discontinue treatment with systemic immunosuppressives and restart in the absence of postoperative infection.²¹ Stopping biologics, in consultation with the surgeon, should also be considered. If there is an intent for the biologics to be eliminated from the system, it should be stopped for at least 2 to 5 half-lives before the surgery and each patient profile and associated morbidity must be considered.²¹

Table 5 presents the summary of recommendations for patients with psoriasis with a risk of comorbidities and patients with psoriasis with comorbid conditions, as well as delivery of care and social and psychological aspects of psoriasis.^36,66,67 Table 6 presents the summary of treatment recommendations for children with psoriasis.⁴⁸

Table 5. Summary of treatment recommendations in patients with comorbidities and on delivery of care, and social and psychological aspects of psoriasis.^36,66,67

Table 6. Treatment recommendations for children with psoriasis.⁴⁸

Considerations for vaccination

While on treatment with systemic immunosuppressants/biologics, vaccination requires special care. Vaccine counselling is an essential component of the treatment plan for psoriasis. Patients should be up-to-date on all immunisations, as recommended by local guidelines.⁶⁸

The following groups should not receive live vaccines:³⁰ (1) patients on systemic immunosuppressants/biologics, and (2) infants up to 6 months of age whose mothers had received biologic treatment beyond 22 weeks of gestation (except certolizumab).⁴⁷

If live vaccination is needed, then it should be administered after stopping the biologics therapy for at least 3 half-lives. Live attenuated zoster vaccine should not be given while on biologics. The recombinant zoster vaccine (SHINGRIXÔ), an inactivated vaccine, can be given while on biologics. In general, systemic immunosuppressants/biologic treatment can be started at least 4 weeks after the administration of a live vaccine.³⁶ Recommendations on when to administer live vaccines based on biological half-life are given in Supplementary Table S3.³⁰

Inactivated vaccines can be given while on systemic immunosuppressants/biologics and, where possible, may be given at least 2 weeks before initiation for an optimal immune response. Response to vaccines is normal or slightly impaired while on systemic immunosuppressants/biologics.³⁶ Live vaccines are to be avoided during systemic immunosuppressants/biologic treatment, including measles–mumps–rubella vaccination, varicella, rotavirus, BCG, yellow fever, oral typhoid and oral polio.⁵³

Limitations of guidelines

These guidelines represent the best evidence at the time the project commenced. The field of therapeutics for psoriasis is rapidly advancing, and the findings from forthcoming studies may necessitate altering the recommendations mentioned in this report.

Treatment should be tailored to individual patients and their specific circumstances. It may be necessary to deviate from these guidelines in specific patients or in special circumstances. Adherence to guidelines may not serve as a defence in a negligence claim. Similarly, deviation from the recommendations should not be considered as negligence.

These guidelines take into consideration the financial implications of treatment, medical assistance and funding. However, there may be changes in these schemes, the clinical evidence surrounding these medications, and side effect profiles when more data emerge.

Guidelines are based on a literature search until December 2019, supplemented with key updates till 31 December 2023. However, newer biologics (guselkumab, risankizumab and spesolimab) and oral deucravacitinib were not included as they received HSA approval after the 2019 literature review and not included as part of the consensus voting and discussion. Published data beyond this date may be a topic for consideration in future guidelines.

CONCLUSION

The practical guidelines developed by the members of the DSS Psoriasis Therapeutic Guidelines Workgroup outline evidence-based recommendations in an easy-to-read format. This can help prescribing dermatologists in achieving good outcomes when managing their patients.

Supplementary materials

Table S1. SIGN grading system: 1999–2012.¹⁸

Table S2. Common topical and nonbiologic systemic psoriasis medications and description for their use along with their earlier FDA categories.^19-30

Table S3. Recommendations on when to administer live vaccine based on half-lives of biologics.³⁰

Fig. S1. Flowchart explaining the process followed in formulating the guidelines.

Acknowledgements

The Dermatological Society of Singapore (DSS) Psoriasis Therapeutic Guidelines Workgroup members would like to acknowledge Professor Christopher Griffiths (Emeritus Professor of Dermatology, University of Manchester and Director, Global Psoriasis Atlas) and Professor Wayne Gulliver (Chair of Dermatology, Faculty of Medicine, Memorial University of Canada, Newfoundland) for their time and expertise in reviewing the DSS Psoriasis Management Guidelines.

REFERENCES

1. World Health Organization. Global report on psoriasis, 2016. https://iris.who.int/handle/10665/204417. Accessed 19 April 2024.
2. Coates LC, Soriano ER, Corp N, et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA): updated treatment recommendations for psoriatic arthritis 2021. Nat Rev Rheumatol 2022;18:465-79.
3. Smith CH, Yiu ZZN, Bale T, et al. British Association of Dermatologists guidelines for biologic therapy for psoriasis 2023: a pragmatic update. Br J Dermatol 2024;190:270-2.
4. Morita A, Tsai T-F, Yee EYW, et al. Efficacy and safety of spesolimab in Asian patients with a generalized pustular psoriasis flare: Results from the randomized, double-blind, placebo-controlled Effisayil^TM 1 study. J Dermatol 2023;50:183-94.
5. Agency for Care Effectiveness. Interleukin inhibitors for treating chronic plaque psoriasis and active psoriatic arthritis, 18 January 2021. Updated on 31 August 2022. https://www.ace-hta.gov.sg/docs/default-source/drug-guidances/interleukin-inhibitors-for-treating-chronic-plaque-psoriasis-and-active-psoriatic-arthritis-pes-(updated-31-aug-22).pdf. Accessed 22 April 2024.
6. Torres T, Chiricozzi A, Puig L, et al. Treatment of Psoriasis Patients with Latent Tuberculosis Using IL-17 and IL-23 Inhibitors: A Retrospective, Multinational, Multicentre Study. Am J Clin Dermatol 2024;25:333-42.
7. Wang X, Zhang M, Chen Y, et al. Risk for Hepatitis B Virus Reactivation in Patients with Psoriasis Treated with Biological Agents: A Systematic Review and Meta-Analysis. Dermatol Ther (Heidelb) 2022;12:655-70.
8. De Brandt E, Hillary T. Comorbid Psoriasis and Metabolic Syndrome: Clinical Implications and Optimal Management. Psoriasis (Auckl) 2022;12:113-26.
9. Hebert AA, Browning J, Kwong PC, et al. Managing pediatric psoriasis: update on treatments and challenges—a review. J Dermatolog Treat 2022;33:2433-42.
10. Lambert JLW, Segaert S, Ghislain PD, et al. Practical recommendations for systemic treatment in psoriasis in case of coexisting inflammatory, neurologic, infectious or malignant disorders (BETA‐PSO: Belgian Evidence‐based Treatment Advice in Psoriasis; part 2). J Eur Acad Dermatol Venereol 2020;34:1914-23.
11. Orlando G, Molon B, Viola A, et al. Psoriasis and Cardiovascular Diseases: An Immune-Mediated Cross Talk? Front Immunol 2022;13:868277.
12. Narbutt J, Niedźwiedź M, Lesiak A, et al. Secukinumab for the Treatment of Psoriasis in Pediatrics: Patient Selection and Acceptability. Patient Prefer Adherence 2023;17:421-31.
13. Chiu H-Y, Chiu Y-M, Chang Liao N-F, et al. Predictors of hepatitis B and C virus reactivation in patients with psoriasis treated with biologic agents: a 9-year multicenter cohort study. J Am Acad Dermatol 2021;85:337-44.
14. World Health Organization. WHO consolidated guidelines on tuberculosis: module 1: prevention: tuberculosis preventive treatment, 25 February 2020. https://www.who.int/publications-detail-redirect/9789240001503. Accessed 19 April 2024.
15. Ministry of Health, Singapore. Subsidised Drug list. https://www.moh.gov.sg/healthcare-schemes-subsidies/subsidised-drug-list. Accessed 28 August 2023.
16. American College of Rheumatology. Psoriatic Arthritis Guideline, 2018. https://rheumatology.org/psoriatic-arthritis-guideline. Accessed 19 April 2024.
17. Psoriasis: assessment and management. London: National Institute for Health and Care Excellence (NICE), 2017. (NICE Clinical Guidelines, No. 153). http://www.ncbi.nlm.nih.gov/books/NBK553610/. Accessed 19 April 2024.
18. Scottish Intercollegiate Guidelines Network. SIGN Grading System 1999–2012. https://www.sign.ac.uk/assets/sign_grading_system_1999_2012.pdf. Accessed 5 May 2022.
19. Koh YP, Tian EA, Oon HH. New changes in pregnancy and lactation labelling: Review of dermatologic drugs. Int J Womens Dermatol 2019;5:216-26.
20. Gottlieb AB, Ryan C, Murase JE. Clinical considerations for the management of psoriasis in women. Int J Womens Dermatol 2019;5:141-50.
21. Kaushik SB, Lebwohl MG. Psoriasis: Which therapy for which patient: Focus on special populations and chronic infections. J Am Acad Dermatol 2019;80:43-53.
22. Puchner A, Gröchenig HP, Sautner J, et al. Immunosuppressives and biologics during pregnancy and lactation: A consensus report issued by the Austrian Societies of Gastroenterology and Hepatology and Rheumatology and Rehabilitation. Wien Klin Wochenschr 2019;131:29-44.
23. Food and Drug Administration. CLOBEX® (clobetasol propionate) Lotion, 0.05%, for topical use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021535Orig1s003,%20021644Orig1s003lbl.pdf. Accessed 4 April 2023.
24. Food and Drug Administration. SORILUX (calcipotriene) foam, 0.005%, for topical use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022563s002lbl.pdf. Accessed 4 April 2023.
25. Food and Drug Administration. ENSTILAR® (calcipotriene and betamethasone dipropionate) Foam, 0.005%/0.064% for topical use. https://www.accessdata.fda.gov/ drugsatfda_docs/label/2015/207589s000lbl.pdf. Accessed 4 April 2023.
26. Food and Drug Administration. OTEZLA® (apremilast) tablets, for oral use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/205437s011lbl.pdf. Accessed 4 April 2023.
27. Murase JE, Heller MM, Butler DC. Safety of dermatologic medications in pregnancy and lactation: Part I. Pregnancy. J Am Acad Dermatol 2014;70:401.e1-401.e14.
28. Food and Drug Administration. NEORAL®. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/050715s027,050716s028lbl.pdf. Accessed 4 April 2023.
29. Food and Drug Administration. METHOTREXATE tablets, for oral use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/040054s015,s016,s017.pdf. Accessed 4 April 2023.
30. Government of Canada. Immunization of immunocompromised persons: Canadian Immunization Guide. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-3-vaccination-specific-populations/page-8-immunization-immunocompromised-persons.html. Accessed 4 April 2023.
31. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: care-based presentations and evidence-based conclusions. J Am Acad Dermatol 2011;65:137-74.
32. Elewski BE, Puig L, Mordin M, et al. Psoriasis patients with psoriasis Area and Severity Index (PASI) 90 response achieve greater health-related quality-of-life improvements than those with PASI 75–89 response: results from two phase 3 studies of secukinumab. J Dermatol Treat 2017;28:492-99.
33. Kerdel F, Zaiac M. An evolution in switching therapy for psoriasis patients who fail to meet treatment goals. Dermatol Ther 2015;28:390-403.
34. Porter ML, Lockwood SJ, Kimball AB. Update on biologic safety for patients with psoriasis during pregnancy. Int J Womens Dermatol 2017;3:21-5.
35. Owczarek W, Walecka I, Lesiak A, et al. The use of biological drugs in psoriasis patients prior to pregnancy, during pregnancy and lactation: a review of current clinical guidelines. Postepy Dermatol Allergol 2020;37:821-30.
36. Smith CH, Jabbar‐Lopez ZK, Yiu ZZ, et al. British Association of Dermatologists guidelines for biologic therapy for psoriasis 2017. Br J Dermatol 2017;177:628-36.
37. Devaux S, Castela A, Archier E, et al. Adherence to topical treatment in psoriasis: a systematic literature review. J Eur Acad Dermatol Venereol 2012;26:61-7.
38. Feldman SR, Camacho FT, Krejci-Manwaring J, et al. Adherence to topical therapy increases around the time of office visits. J Am Acad Dermatol 2007;57:81-3.
39. Ibrahim GH, Buch MH, Lawson C, et al. Evaluation of an existing screening tool for psoriatic arthritis in people with psoriasis and the development of a new instrument: the Psoriasis Epidemiology Screening Tool (PEST) questionnaire. Clin Exp Rheumatol 2009;27:469-74.
40. Elmamoun M, Leung YY, O’Sullivan D, et al. Using Acute-phase Reactants to Inform the Development of Instruments for the Updated Psoriatic Arthritis Core Outcome Measurement Set. J Rheumatol 2019;46:266-73.
41. Ritchlin CT, Colbert RA, Gladman DD. Psoriatic Arthritis. N Engl J Med 2017;376: 957-70.
42. Generali E, Scirè CA, Favalli EG, et al. Biomarkers in psoriatic arthritis: a systematic literature review. Expert Rev Clin Immunol 2016;12:651-60.
43. Eder L, Gladman DD. Predictors for clinical outcome in psoriatic arthritis – what have we learned from cohort studies? Expert Rev Clin Immunol 2014;10:763-70.
44. Gossec L, Baraliakos X, Kerschbaumer A, et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update. Ann Rheum Dis 2020;79:700-12.
45. Sakkas LI, Alexiou I, Simopoulou T, et al. Enthesitis in psoriatic arthritis. Semin Arthritis Rheum 2013;43:325-34.
46. Rose S, Toloza S, Bautista-Molano W, et al. Comprehensive Treatment of Dactylitis in Psoriatic Arthritis. J Rheumatol 2014;41:2295-300.
47. Götestam Skorpen C, Hoeltzenbein M, Tincani A, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis 2016;75:795-810.
48. Menter A, Cordoro KM, Davis DMR, et al. Joint American Academy of Dermatology–National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis in pediatric patients. J Am Acad Dermatol 2020;82:161-201.
49. Bodemer C, Kaszuba A, Kingo K, et al. Secukinumab demonstrates high efficacy and a favourable safety profile in paediatric patients with severe chronic plaque psoriasis: 52‐week results from a Phase 3 double‐blind randomized, controlled trial. J Eur Acad Dermatol Venereol 2021;35:938-47.
50. Food and Drug Administration. COSENTYX® (secukinumab) injection, for subcutaneous or intravenous use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761349s000lbl.pdf. Accessed 19 April 2024.
51. Paller AS, Seyger MMB, Alejandro Magariños G, et al. Efficacy and safety of ixekizumab in a phase III , randomized, double‐blind, placebo‐controlled study in paediatric patients with moderate‐to‐severe plaque psoriasis (IXORA ‐ PEDS). Br J Dermatol 2020;183:231-41.
52. Food and Drug Administration. TALTZ (ixekizumab) injection, for subcutaneous use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125521s020lbl.pdf. Accessed 19 April 2024.
53. Food and Drug Administration. STELARA™ (ustekinumab). https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125261lbl.pdf. Accessed 19 April 2024.
54. Lansang P, Bergman JN, Fiorillo L, et al. Management of pediatric plaque psoriasis using biologics. J Am Acad Dermatol 2020;82:213-21.
55. Grozdev IS, Van Voorhees AS, Gottlieb AB, et al. Psoriasis in the elderly: From the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol 2011;65: 537-45.
56. Sandhu VK, Ighani A, Fleming P, et al. Biologic Treatment in Elderly Patients With Psoriasis: A Systematic Review. J Cutan Med Surg 2020;24:174-86.
57. Nast A, Amelunxen L, Augustin M, et al. S3 Guideline for the treatment of psoriasis vulgaris, update – Short version part 2 – Special patient populations and treatment situations. J Dtsch Dermatol Ges 2018;16:806-13.
58. Ang MLT, Chan SM, Cheng LT-E, et al. Singapore tuberculosis (TB) clinical management guidelines 2024: A modified Delphi adaptation of international guidelines for drug-susceptible TB infection and pulmonary disease. Ann Acad Med Singap 2024;53:170-86.
59. Plachouri K-M, Georgiou S. Special aspects of biologics treatment in psoriasis: management in pregnancy, lactation, surgery, renal impairment, hepatitis and tuberculosis. J Dermatolog Treat 2019;30:668-73.
60. Megna M, Lauletta G, Tommasino N, et al. Management of Psoriasis Patients with Serious Infectious Diseases. Adv Ther 2024;41:2099-111.
61. Piaserico S, Messina F, Russo FP. Managing Psoriasis in Patients with HBV or HCV Infection: Practical Considerations. Am J Clin Dermatol 2019;20:829-45.
62. Lau G, Yu M-L, Wong G, et al. APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy. Hepatol Int 2021;15:1031-48.
63. Reddy KR, Beavers KL, Hammond SP, et al. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology 2015;148:215-9.
64. Martinello M, Naggie S, Rockstroh JK, et al. Direct-acting antiviral therapy for treatment of acute and recent hepatitis C virus infection: a narrative review. Clin Infect Dis 2023;77:S238-44.
65. Plachouri KM, Georgiou S. Challenges in the treatment of psoriasis with biologics: vaccination, history of malignancy, human immunodeficiency virus (HIV) infection, and pediatric psoriasis. Int J Dermatol 2019;58:1008-13.
66. Elmets CA, Lim HW, Stoff B, et al. Joint American Academy of Dermatology–National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis with phototherapy. J Am Acad Dermatol 2019;81:775-804.
67. Takeshita J, Shin DB, Ogdie A, et al. Risk of Serious Infection, Opportunistic Infection, and Herpes Zoster among Patients with Psoriasis in the United Kingdom. J Invest Dermatol 2018;138:1726-35.
68. The National Psoriasis Foundation. Report Vaccinating While On Biologics Requires Special Care. https://www.psoriasis.org/media/press-releases/report-vaccinating-while-biologics-requires-special-care. Accessed 2 December 2022.