What are the recommended treatment guidelines for an adult patient in India with plaque (vulgar) psoriasis?

Treatment Guidelines for Psoriasis Vulgaris in India

For mild psoriasis (<5% body surface area), start with combination calcipotriene/betamethasone dipropionate applied once daily for 4 weeks; for moderate-to-severe disease (≥5% BSA or PASI ≥10 with DLQI >10), initiate adalimumab 80 mg subcutaneous on Day 1, followed by 40 mg at Week 1, then 40 mg every 2 weeks thereafter. 1, 2

Disease Severity Assessment

• Psoriasis severity is classified as mild when <5% body surface area is involved, or **moderate-to-severe** when ≥5% BSA or PASI ≥10 with DLQI >10. 2
• High-impact anatomic sites (face, scalp, palms/soles, nails, genitalia) markedly reduce quality of life even with limited overall body surface involvement and warrant more aggressive treatment regardless of total BSA. 2
• Patients with psoriatic arthritis of any severity require biologic therapy regardless of skin disease extent. 3

Mild Psoriasis: Topical Therapy Algorithm

First-Line: Combination Calcipotriene + Betamethasone

• Fixed-combination calcipotriene/betamethasone dipropionate applied once daily for 4 weeks is the most effective topical approach, providing superior efficacy to monotherapy while reducing adverse effects of either agent alone. 2, 4
• This combination achieves maximal improvement within 4 weeks in the majority of patients. 2
• The once-daily two-compound product is the most practical solution for chronic plaque psoriasis. 4

Alternative Maintenance Regimens

• Apply vitamin D analogues twice daily on weekdays combined with high-potency topical corticosteroids twice daily on weekends for maintenance therapy. 2
• Morning high-potency topical corticosteroids with evening topical vitamin D analogues is an effective alternative regimen. 2
• Long-term use of topical vitamin D analogues (up to 52 weeks) is safe and recommended for mild to moderate psoriasis. 2

Corticosteroid Potency Selection by Site

• For trunk and extremities, use moderate-to-ultrahigh-potency corticosteroids (class 1–5) for up to 4 weeks. 2
• For facial, intertriginous, and atrophy-prone areas, use lower-potency corticosteroids. 2
• Ultrahigh-potency class 1 agents (clobetasol, halobetasol) achieve clearance in 58%–92% of thick, chronic plaques. 2

Scalp Psoriasis Specific Treatment

• Apply calcipotriene foam or calcipotriene plus betamethasone dipropionate gel for 4-12 weeks as first-line treatment. 2
• Generic clobetasol propionate 0.05% solution applied twice daily is highly effective, widely available, and among the least expensive prescription treatments for scalp psoriasis. 2
• Class 1–7 corticosteroids can be employed on the scalp for a minimum of 4 weeks as both initial and maintenance therapy. 2

Critical Topical Therapy Pitfall

• Avoid simultaneous use of salicylic acid with calcipotriene, as the acid pH inactivates calcipotriene and reduces its effectiveness. 1

Moderate-to-Severe Psoriasis: Biologic Therapy Algorithm

Patient Eligibility Criteria

• Patients are eligible for biologic therapy when they meet all of the following: PASI ≥10 AND DLQI >10, AND have failed, have contraindications to, or are intolerant of at least one conventional systemic therapy (methotrexate, cyclosporine, or PUVA). 1, 3

First-Line Biologic Selection

Adalimumab (Preferred First-Line):

• Dose: 80 mg subcutaneous on Day 1, then 40 mg at Week 1, then 40 mg every 2 weeks thereafter. 1, 2, 3, 5
• Efficacy: Achieves PASI 75 in 71% of patients at week 16 (versus 7% with placebo). 1, 2, 3
• Strongly recommended for palmoplantar psoriasis, nail psoriasis, scalp psoriasis, and psoriatic arthritis regardless of overall skin disease severity, as it treats both skin and joint symptoms and inhibits radiographic joint damage. 1, 3
• Assess treatment response at 16 weeks. 3

Alternative First-Line Options (High-Certainty Evidence):

• Infliximab, bimekizumab, ixekizumab, or risankizumab achieve PASI 90 responses in 70-80% of patients and are recommended as first-line systemic therapy for severe plaque psoriasis. 2

Infliximab:

• Dose: 5 mg/kg IV at weeks 0,2,6, then every 8 weeks. 1, 2, 3
• Efficacy: Achieves PASI 75 in 79-80% of patients by week 10. 1, 2, 3
• Requires concomitant methotrexate to reduce immunogenicity and prevent antibody formation; without it, approximately 19% of patients develop anti-infliximab antibodies. 1, 2, 3
• Assess treatment response at 10-14 weeks. 3

Etanercept:

• Dose: 50 mg subcutaneous twice weekly for 12 weeks, then 50 mg once weekly maintenance. 1, 2, 3
• Efficacy: Achieves PASI 75 in 48-66% of patients at week 12. 1, 2, 3
• Recommended for nail psoriasis and scalp psoriasis. 3
• Assess treatment response at 12 weeks. 3

Bimekizumab, Ixekizumab, Risankizumab:

• PASI 90 achieved in 80-84% of treated patients (relative risk ≈ 29-30 versus placebo). 2

Ustekinumab (IL-23 Inhibitor)

• Dose: 45 mg subcutaneous at weeks 0,4, then every 12 weeks for patients ≤100 kg; 90 mg subcutaneous at the same schedule for patients >100 kg. 2
• For inadequate response, increase to 90 mg or shorten interval to every 8 weeks. 2
• Site-specific efficacy: In palmoplantar psoriasis, 90 mg yields 67% clearance versus 9% with 45 mg; in nail disease, median 100% NAPSI improvement observed by week 40 with 44.7% achieving full nail clearance. 2

Combination Strategies to Enhance Biologic Efficacy

• Adding high-potency topical corticosteroids to etanercept for 12 weeks accelerates plaque clearance (Level I evidence, Strength A). 1, 2, 3
• Calcipotriene/betamethasone dipropionate combined with adalimumab for 16 weeks accelerates clearance (Strength B). 1, 2, 3
• All topical corticosteroids can be combined with any biologic for treatment of moderate to severe psoriasis. 1
• Methotrexate combinations with etanercept, adalimumab, and infliximab reduce immunogenicity and prevent antibody formation. 3
• Adding methotrexate or acitretin to ustekinumab may improve therapeutic outcomes. 2

Treatment Response Assessment

• Treatment success is defined as achieving PASI 75 (75% improvement) or PASI 50 (50% improvement) AND DLQI improvement >5 points. 1, 3
• Evaluate response at 12-16 weeks depending on the biologic agent used. 1, 3

Management of Treatment Failure

• Failure to respond to one TNF-α inhibitor does not preclude a successful response to a different TNF-α inhibitor, although overall efficacy may be reduced. 2
• Failure of any biologic does not preclude a successful response to ustekinumab. 2
• Secondary loss of response can occur with any biologic; concomitant methotrexate reduces antidrug antibody formation and improves drug survival. 2
• When retreating after a drug holiday of >3-4 half-lives or during a flare, repeat loading doses are advised; a minority of patients may not recapture their prior response magnitude. 2

Conventional Systemic Agents (When Biologics Unavailable)

Cyclosporine

• Indicated for severe, recalcitrant psoriasis (especially erythrodermic or generalized pustular forms). 2
• Dose: 2.5-5.0 mg/kg/day in two divided doses. 2
• At 5 mg/kg/day, 65% achieve clear/almost clear status after 8 weeks; 50-70% achieve PASI 75 after 8-16 weeks. 2
• Short-term courses of 3-4 months preferred; US approval permits up to 1 year continuous use. 2
• Monitor blood pressure and serum creatinine every 2 weeks for 3 months, then monthly; monthly CBC, liver enzymes, lipids, electrolytes. 2
• Contraindications: Impaired renal function, uncontrolled hypertension, active malignancy, concurrent PUVA/UVB, methotrexate, or other immunosuppressives. 2
• Avoid grapefruit juice (pharmacokinetic interaction). 2

Acitretin

• PASI 75 achieved in 23% of patients at 8 weeks with 50 mg/day dose; PASI 50 achieved in 75% at 6 months and 88% at 12 months. 2
• Can be combined with calcipotriene to enhance efficacy. 1

Methotrexate

• Can be combined with topical calcipotriene for moderate to severe psoriasis (Level I evidence, Strength A). 1
• Associated with a lower incidence of serious adverse events compared with most biologic agents, although the evidence is of very low certainty. 2

Mandatory Safety Monitoring for All Biologics

Tuberculosis Screening (Critical)

• Perform PPD skin test or interferon-γ release assay before initiating any biologic; treat latent TB before starting therapy. 2, 5
• Ongoing monitoring for active TB is required throughout biologic treatment, even after a negative baseline test. 1, 2, 5
• Discontinue biologic if a patient develops a serious infection or sepsis during treatment. 5

Infection Risk

• Increased risk of serious infections leading to hospitalization or death, including tuberculosis, bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections due to other opportunistic pathogens. 5
• For patients who develop a systemic illness on biologics and reside or travel to regions where mycoses are endemic, consider empiric antifungal therapy. 5

Malignancy Risk

• Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers. 5
• Post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have occurred in adolescent and young adults with inflammatory bowel disease treated with TNF blockers. 5
• Incidence of malignancies was greater in biologic-treated patients than in controls. 5

Critical Pitfalls to Avoid

• Never use systemic corticosteroids (prednisone) for psoriasis due to poor long-term efficacy and severe rebound flares upon discontinuation. 1, 3
• Do not delay biologics in patients with >5% BSA involvement who meet eligibility criteria. 1, 3
• Infliximab intervals should not be extended beyond 8 weeks, and methotrexate should always be added to infliximab to prevent antibody formation. 3
• Consider systemic or phototherapy even for limited BSA involvement if the patient has symptomatic psoriasis with pain, bleeding, or itching. 2