New Systemic Treatments for Psoriasis

S. Pirzada, MD¹; Z. Tomi, MD, FRCPC²; W. Gulliver, MD, FRCPC2,³

¹Dalhousie University, Halifax, Canada
²Division of Dermatology, Department of Medicine, Memorial University, St. John’s, Canada
³Newlab Research, St. John’s, Canada

The Disease

Psoriasis is a chronic, immune-mediated disease, affecting more than 1 million adults in Canada with more than 250,000 new cases diagnosed each year in North America.[Gupta AK, et al. J Cutan Med Surg 8 Suppl:3-7 (2004 Aug).] Up to 35% of people with psoriasis have moderate-to-severe disease, affecting 2%–10% of total body surface area.[Thomas VD, et al. J Am Acad Dermatol 53(2):346-51 (2005 Aug).] Up to 30% of Canadians with psoriasis develop psoriatic arthritis (PsA), [The Arthritis Society. Psoriatic Arthritis.] and half of those with PsA are estimated to have already experienced serious joint damage (e.g., bone loss) upon first diagnosis. As this can lead to progressive and often irreversible bone and joint destruction, early diagnosis is important to prevent long-term effects. The need for effective and safer therapies has been increasing as more studies show the serious
psychosocial and sometimes debilitating effects of moderate-to-severe psoriasis. However, even psoriasis confined to palms or soles, although covering a small area, can cause difficulty for patients.

Standard Systemic Therapies for Psoriasis

The standard systemic therapies for psoriasis are methotrexate, cyclosporine, oral retinoids such as acitretin (Soriatane^®), psoralen + UVA (PUVA), and retinoid PUVA (RePUVA). Less commonly used therapies are hydroxyurea (Hydrea^®) and mycophenolate mofetil (CellCept^®).

New Systemic Therapies for Psoriasis

Biologics are new systemic therapies that have given dermatologists and rheumatologists a new tool to treat psoriasis, with several undergoing clinical trials in Canada, the US, and Europe. Biologics are immunomodulators and bioengineered proteins (such as antibodies, fusion proteins, or recombinant cytokines) that target the pathological effects of T cells directly. Targeted biologic therapies are designed to:

• inhibit T cell activation and migration.
• eliminate activated T cells.
• inhibit postsecretory cytokines, e.g., antitumor necrosis factor (antiTNF) agents.
• induce immune deviation. [Lui H, et al. J Cutan Med Surg 8 Suppl:8-13 (2004 Aug).]

Biologics approved by the US FDA and Health Canada to treat psoriasis and psoriatic arthritis (PsA) are infliximab (Remicade^®) and etanercept (Enbrel^®). Efalizumab (Raptiva^®) and alefacept (Amevive^®) are indicated only for psoriasis, and adalimumab (Humira^®) is currently approved for PsA only. The availability of biologics has brought about a shift in the treatment approach to psoriasis. In the past, a more stepwise approach was used with a topical being prescribed first and then moving to UV light and/ or systemic drugs. Now the trend is to use the most effective treatment early in the course of the disease. In 2005, Canadian Consensus Guidelines were published recommending that all appropriate treatment options, including biologic agents, be considered together, and a patient’s specific characteristics and needs be taken into account.[Guenther L, et al. J Cutan Med Surg 8(5):321-37 (2004 Sep-Oct).] The choice of treatment should depend on the severity of the psoriasis and its impact on the patient’s quality of life. AntiTNF drugs are particularly effective for treating PsA.

AntiTNF Agents

Infliximab (Remicade®)

[Infliximab (Remicade^®) Package Insert. Centocor, Inc., Malvern, PA (2002).]

• Dosage: 5mg/kg IV over 2 hours at weeks 0, 2, 6, then 5mg/kg every 8 weeks.
• Common side-effects: nausea, abdominal pain, back pain, arthralgia, fatigue, headache.
• More serious side-effects: hypersensitivity reactions, infusion reactions, worsening of congestive heart failure, infections, tuberculosis, leukopenia, neutropenia, thrombocytopenia, pancytopenia, invasive fungal infections, and a lupus-like syndrome.
• Relative efficacy using Psoriasis Area Severity Index (PASI): PASI 75 achieved in 75% of patients at week-14 and 60% at week-26; PASI 90 seen in 39% at week-26. Statistically significant reduction in PASI compared with placebo by 2 weeks after start. The PASI response was generally maintained through week 54. Reich, et al. reported a PASI 75 in 80% at week-10, 82% at week-24 and 61% at week-50; PASI 90: 57% at week-10, 58% at week-24, and 45% at week-50.[Reich K, et al. Lancet 366(9494):1367-74 (2005 Oct).]
• Infliximab is unique among available antiTNF biologic therapies, as specially trained nurses administer, monitor and assist the patients during each infusion in clinic settings that are located throughout Canada.
• This drug is the most potent antipsoriatic agent available at this time.

Etanercept (Enbrel^®)

[Etanercept (Enbrel) Package Insert. Immunex Corp., Seattle, WA (2004).]

• Dosage: 50mg SC biweekly for 12 weeks, then 50mg SC weekly.
• Common side-effects: injection-site reactions, cough and respiratory symptoms, infections, headaches, and positive antinuclear antibody.
• More serious side-effects: allergic reactions, pancytopenia, new onset or exacerbation of CNS demyelinating disorders(rare), increased incidence of lymphoma (twice the general risk), and infections.
• Relative efficacy using PASI: PASI 75 seen in 47% of patients at 3 months and 54% at 6 months; PASI 50 achieved in 71% at 3 months; Physician’s Global Assessment (PGA) “almost clear” or “clear” attained in 47% at 3 months. Median time to PASI 50 and PASI 75 was 1 and 2 months respectively, after start. Seventy-seven percent of patients who achieved a PASI 75 at 3 months maintained their improvement at month 6 with 25mg SC weekly.[Thomas VD, et al. J Am Acad Dermatol 53(2):346-51 (2005 Aug).]
• This drug shows efficacy in psoriasis and PsA. It is used continuously, but shows no rebound if it is used intermittently.

T-cell Modulators

Efalizumab (Raptiva^®)

[Thomas VD, et al. J Am Acad Dermatol 53(2):346-51 (2005 Aug).]

• Dosage: begin 0.7mg/kg SC then hold at 1mg/kg (max 200mg) weekly (maintenance therapy).
• Common side-effects: headache, flu-like symptoms with first dose (e.g., fever, headache, myalgia, nausea), infection, elevated alkaline phosphatase.
• More serious side-effects: infection, malignancy, thrombocytopenia, worsening of psoriasis through rebound effect.
• Relative efficacy using PASI: PASI 75 achieved in 22%–39%, and PASI 50 attained in 52%–61% at 12-weeks; PGA “almost clear” or “clear” seen in 19%–32% at 12-weeks. PASI 50 began 4 weeks after start. Seventy-seven percent of patients achieving PASI 75 maintained their improvement through a second 12-week treatment period.
• This drug acts quickly and needs to be used continuously. The benefits long term appear to be maintained.

Alefacept (Amevive^®)

[Thomas VD, et al. J Am Acad Dermatol 53(2):346-51 (2005 Aug).]

• Dosage: 15mg IM weekly x 12 weeks; wait 12 weeks, then consider a second 12-week course provided CD4+ T lymphocyte counts are within normal range.
• Common side-effects: cough, dizziness, nausea, myalgia, chills, pharyngitis, pruritus, injection site reactions, transaminitis.
• More serious side-effects: lymphopenia (10% IM), malignancies, serious infections, hypersensitivity, transaminase (rare), cardiovascular events.
• Relative efficacy using PASI: PASI 75 achieved in 21%, and PASI 50 attained in 42% at week-14 (2 weeks postdosing); PGA “almost clear” or “clear” was 14% at week-14; PASI 50 began 60 days after start. Most patients maintained at least a PASI 50 through the 3-month observation period.
• This drug is used intermittently and can have a prolonged benefit for those patients in which it is effective.

Conclusions

Biologics are one of the more effective and relatively safe options for long-term control of psoriasis. They have reduced the time needed to clear the signs of chronic disease, and are effective in maintaining a disease-free state for longer durations. Biologics can safely be used with other treatment modalities (i.e., methotrexate, cyclosporine, acitretin and hydroxyurea). Clinicians should assess patients’ psoriasis and their psychosocial and quality of life issues, before deciding on the optimum treatment modality. With the availability of biologics, all treatment options should be considered equally.

Dermatologic Diagnostic Challenge

Question: A 32 year-old female presented in the summer with a pruritic bullous eruption on bilateral dorsal feet of 2 weeks’ duration. She is a nurse who is regularly in contact with patients. She is otherwise healthy, although a recent ankle sprain resulted in a prescription for a topical nonsteroidal anti-inflammatory medication.

What is the diagnosis?

a.

• Porphyria cutanea tarda

b.

• Psoriasis

c.

• Allergic contact dermatitis

d.

• Bullous impetigo

e.

Bullous scabies