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110-6 SECTION 14 Dermatologic Disorders obtained at baseline and CBC and LFTs monitored periodically during therapy. 1,3,4 ✓ ✓ Ustekinumab (Stelara) is an IL-12/23 monoclonal antibody that selectively targets IL-12 and IL-23, two cytokines that play a role in the pathogenesis of psoriasis. It binds to their shared p40 protein subunit, thus preventing interaction with their cell surface IL-12Rβ1 receptor. 12,13 It appears to provide a rapid response that is sustained for a year with continuous treatment. It is given subcutaneously at weeks 0 and 4, and then every 12 weeks as maintenance therapy. The manufacturer recommends dosing by body weight, with patients weighing 220 lb (100 kg) or less receiving 45 mg and those weighing more than 220 lb (100 kg) receiving 90 mg. Common side effects include upper respiratory infections, headache, and tiredness. Serious side effects include those seen with other BRMs such as serious infections (e.g., TB, fungal, viral) and cancer risk; in addition, a reversible posterior leukoencephalopathy syndrome (RPLS) has been reported. • Intralesional corticosteroid injections (triamcinolone acetonide 5–10 mg/mL or triamcinolone hexacetonide 5 mg/mL) may be useful for small, localized, recalcitrant plaques. • Antihistamines such as hydroxyzine 10–25 mg po TID and 50–75 mg po at bedtime should be given as adjunctive therapy to relieve the pruritus. Hydroxyzine also has anxiolytic properties that may be useful in this patient. • There are many natural health products/alternative treatments for psoriasis, including omega-3 fish oil supplements, cleansing diets, emu oil, lecithin, a protein extract XP-828L, and Kalawalla (Polypodium leucotomos 50:1 standardized extract). Limited clinical studies with some of these treatments (e.g., omega-3 fish oil supplements) seem promising, and there is limited ongoing research. 6 At this time it is too early to make population-based recommendations for using these products (see the section “Clinical Course: Alternative Therapy” for more information about alternative therapies). Optimal Plan 4. What drug regimen is best suited for treating this flare-up of the patient’s psoriasis and its related symptoms? • The patient has failed topical and photochemotherapies with the exception of SCAT for defined limited lesions, and his current regimen of cyclosporine alternating with acitretin appears to be inadequate. It is important to remember that the patient is on rotational systemic therapy in combination with topical and photochemotherapy. Although rotational systemic therapy is not currently used by most dermatologists, it has been useful in this case for minimizing cyclosporine toxicity. • It would be appropriate at this point to consider the use of a biologic agent, either as monotherapy or in combination with other therapies. Alefacept, adalimumab, infliximab, etanercept, and ustekinumab are approved by the US FDA and Health Canada for plaque psoriasis. ✓✓ Etanercept, infliximab, and adalimumab appear to have a higher efficacy rate than alefacept. Adalimumab appears to provide sustained efficacy over at least 1 year, whereas efficacy becomes variable over time for infliximab. ✓✓ Alefacept, although limited in efficacy, may lead to sustained complete or incomplete remissions in some patients. ✓✓ Infliximab, although highly efficacious initially even for severe cases, may lose efficacy if discontinued and reinitiated, or if used beyond the first year of continuous treatment. ✓✓ Etanercept, adalimumab, or infliximab would be more convenient to administer than alefacept since patients can be taught to self-inject the subcutaneous doses, whereas alefacept therapy would require weekly clinic visits for IM administration. ✓✓ Three cost–efficacy analyses conducted in 2005, 2007, and 2009 found that the cost–benefit of different biologics is quite variable. The most recent clinical and economic review was conducted in 2009 for adalimumab, etanercept, infliximab, ustekinumab, and efalizumab. 14 This review found that the cost per responder achieving a PASI 75 response at 12 weeks was lowest for adalimumab and highest for alefacept, based on the pooled number needed to treat (NNT) to obtain benefit found at 1.3 (infliximab), 1.5 (ustekinumab 90 mg), 1.6 (adalimumab and ustekinumab 45 mg), 2.3 (etanercept), 4.1 (efalizumab—now off the market in the United States and Canada), and 5.6 (alefacept). The annual cost per patient was also lowest for adalimumab, followed by etanercept, ustekinumab, alefacept (two courses), and infliximab. This analysis suggests that there are favorable cost and benefits, particularly with some newer biologics such as adalimumab being the least expensive and most cost-effective. ✓✓ With respect to adverse effects, alefacept may be the safest, but it commonly causes lymphopenia and CD4 counts must be monitored. The TNF-α inhibitors adalimumab, etanercept, and infliximab rarely cause hematologic side effects such as thrombocytopenia but have greater concerns regarding serious infections including reactivation of TB and opportunistic infections. Cases of multiple sclerosis and other central nervous system disorders have also been observed in association with etanercept and other medications that target TNF-α, as is the risk of worsening CHF and new-onset CHF. Infliximab has been associated rarely with cases of cholecystitis and autoimmune hepatitis, which may be a class effect for TNF-α inhibitors. None of the agents is nephrotoxic. ✓✓ Based on the above considerations, adalimumab would be an appropriate choice for an initial trial of a biologic agent (as monotherapy) in this patient, due to its efficacy, lower maintenance cost, and ease of administration. ✓✓ Administer adalimumab 80 mg subcutaneously in the first week, then 40 mg the following week, and thereafter 40 mg every other week continuously. 3,4 ✓✓ The patient could be taught to self-administer the adalimumab dose. • The cyclosporine could be tapered off over 1 month for a smoother transition. • If the patient fails to respond adequately after a 12-week trial of the first biologic agent used (i.e., adalimumab in this case), another biologic (either another anti-TNF agent or another biologic agent) should be tried. • Reverting to methotrexate and increasing its dose is not an appropriate option because a previous dosage increase had not been beneficial and he has already received a cumulative lifetime dose of 2.2 g, although a recent liver biopsy showed no hepatocellular changes as yet. Copyright © 2011 by The McGraw-Hill Companies, Inc. All rights reserved.
110-7 • In addition to systemic therapy, topical therapy for the scalp should be given. An appropriate regimen is salicylic acid 10% in bath oil applied nightly to the scalp and covered with a shower cap overnight plus a tar shampoo used three times weekly until the scalp lesions clear. An alternative therapy is betamethasone 0.1% lotion or 0.12% foam (Luxiq) for the scalp applied twice daily. Because the foam melts only when it reaches body temperature, steroid delivery will be to the scalp and not hair. The foam is easy to apply and has high patient preference. If this is inadequately effective, topical clobetasol propionate 0.05% foam (Olux) could be tried. • Continuation of SCAT to thickly crusted lesions would be beneficial. A 4% anthralin paste is applied twice daily for 2 hours and then wiped off. This should be continued until improvement is seen. • Hydroxyzine 10–25 mg po TID and 50–75 mg at bedtime should be given as adjunctive therapy for its antipruritic and anxiolytic effects. Outcome Evaluation 5. How should you monitor the therapy you recommended for efficacy and adverse effects? Efficacy monitoring: • Psoriatic lesions do not improve overnight. However, some improvement should be apparent within 1–2 weeks for topical therapies and within 2–8 weeks for systemic or biologic therapies. With certain agents, more rapid responses (e.g., 2–4 weeks) are typical—this is true for cyclosporine, adalimumab, infliximab, and ustekinumab. Scalp lesions should have less scaling and erythema (as a result of salicylic acid and tar shampoo treatments), and the thickly crusted lesions on his body should be reduced (as a result of SCAT treatment) within 1–2 weeks. • He should see a definite overall improvement by 12 weeks. If not, the biologic agent is not effective. If this occurs, switching to another biologic agent may still be beneficial. • His pruritus should improve within 24–48 hours of starting hydroxyzine therapy. • General monitoring: If the drug is effective, and the patient’s skin is cleared of psoriatic lesions, it would be important at that point to provide routine dermatologic care. This would include examining the skin and screening for other skin lesions (e.g., skin cancers), especially in the patient who has received PUVA or UVB or has prolonged exposure to natural sunlight. Adalimumab adverse effects monitoring: • Monitor for TB. Baseline PPD is required. Annual PPD should be considered. • Monitor CBC and differential at baseline and periodically (e.g., every 2–3 months). • Monitor LFTs at baseline and periodically (e.g., every 2–3 months). • Monitor for signs of infection during therapy. Some serious acute infections (e.g., opportunistic fungal infections) and reactivation of latent chronic infections (e.g., TB) have been reported. • Other possible adverse effects include mild constitutional symptoms (headache, chills, fever, nausea, and myalgia), worsening CHF or new-onset CHF, lupus without renal or CNS complications, and multiple sclerosis. 3 • Periodic history and physical examination are recommended while on treatment. 3 Hydroxyzine adverse effects: • Sedation is the most common side effect with first-generation antihistamines, especially with the phenothiazine and aminoalkyl ether subgroups. Hydroxyzine is a piperazine derivative with less marked sedating effects. If drowsiness is excessive, switch to a second-generation agent such as loratadine. • Other adverse effects include dizziness or incoordination, GI complaints, and anticholinergic effects such as dry mucous membranes, dysuria, and urinary retention. Patient Education 6. What information should be provided to the patient to enhance compliance and ensure successful therapy? General information: • There should be less scaling and redness of your scalp lesions and a reduction in the thickly crusted areas within 1–2 weeks. You should notice a general improvement in your condition by 6–12 weeks. Your palms, soles, elbows, and knee areas may take longer to clear. • It is important to keep all follow-up appointments with your physician. Adalimumab: • You will be taught how to inject the dose subcutaneously (under the skin). • Some pain at the injection site may occur. • This medication may rarely cause white blood cells to decrease in number. You will have regular blood tests to monitor for this. • Headaches, chills, fever, nausea, and muscle pains can also occur; contact your physician if these become troublesome or persistent. • Because this drug suppresses your immune system, you may be at greater risk of infections, including TB or other serious infections. Let your physician know as soon as possible if you develop a persistent fever. • Other adverse effects can also happen but are rare. These include hepatitis, heart failure, multiple sclerosis, and lupus. You should keep regular clinic appointments and contact your physician if you have any concerns between appointments. Hydroxyzine: • Take one capsule three times daily and two capsules at bedtime for itching. • Itchiness should be relieved within several hours and definitely within 1–2 days. • This medication may cause drowsiness, dry mouth, and problems with urination. If you become too drowsy, other medications are available but they are more expensive. Contact the clinic if any of these effects are too bothersome or if the itchiness is not relieved. SCAT: • While wearing gloves, apply the anthralin paste only on the thickly crusted areas. Leave the paste on for 2 hours and then wipe it off. • Contact us if you notice severe burning. CHAPTER 110 Psoriasis Copyright © 2011 by The McGraw-Hill Companies, Inc. All rights reserved.
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