Oral Therapy for Psoriasis John Koo, MD, FAAD, Marwa Hakimi, MD
Dr. Koo and Dr. Hakimi provided us with an informative discussion on traditional oral therapies for psoriasis, focusing on the use of cyclosporine and acitretin. Neoral (cyclosporine modified) is preferred over the conventional formulation Sandimmune (SIM), given its increased bioavailability, more predictable absorption, and higher percent of patients achieving remission on therapy. Dr. Koo’s three main clinical pearls for cyclosporine are: do not exceed a total of 5 mg/kg/day; do not allow the creatinine to increase by greater than 30%; and do not use continuously for longer than 10 years. Cyclosporine may be started at a high dose approach at 4-5 mg/kg/day which is favored in the U.S., or a low dose approach at 2.5 mg/kg/day which is favored in Europe. High starting dose may be especially beneficial as a “crisis buster” for patients experiencing a rapid flare, erythrodermic patients, or recalcitrant cases that have failed many treatment modalities. Cyclosporine should not be discontinued abruptly. Rather, the dose should be tapered down and another treatment modality should be optimally therapeutic by the time tapering of cyclosporine is initiated.
Acitretin (Soriatane) has been shown to be helpful in prevention of non-melanoma skin cancers, but may also be successful as psoriasis monotherapy for patients with pustular psoriasis and in elderly patients. Other patients to consider include those who are not good candidates for biologics, patients receiving phototherapy, and patients who are not in a rush for improvement. Staying at low dose such as 25 mg per day or less appears to suggest successful effects with % BSA involvement reduction and lower incidence of side effects. Of note, 25 mg of acitretin may be added to a patient whose phototherapy has already been maximized in terms of dosimetry. In these cases, it is important to decrease the dosimetry by 50% to avoid burn. Acitretin may take 3 months or longer to show benefit in psoriasis patients, and may be most effective in combination with other treatments as a therapeutic enhancer.
Hyperpigmentation and Hypopigmentation Pearl Grimes, MD, FAAD
We received a wonderful update on hyperpigmentation and hypopigmentation from Dr. Pearl Grimes. Dr. Grimes suggests a multimodal approach to the treatment of melasma, which has a complex pathogenesis leading to a photodamage phenotype. While post-inflammatory hyperpigmentation can be “cured,” melasma patients should be counseled that they will likely require maintenance treatment. Visible light is implicated in the development of hyperpigmentation, with Opsin-3 (OPN3) as the key sensor in melanocytes responsible for stimulating persistent pigmentation. Iron oxides block short wavelengths of visible light and have been shown to have a statistically significant strong anti-pigmentation effect. Dr. Grimes recommends tinted sunscreen or makeup foundations containing high content iron oxide (at least 3.5-5%) such as Dermablend. In terms of topical lighteners, triple combination products have been shown to be most effective (e.g. hydroquinone, tretinoin, and fluocinolone). Other effective treatments include topical cysteamine cream, oral tranexamic acid, and Polypodium Leucotomas extract. Glutathione (Lyposomal), vitamin E, niacinamide (oral or topical), pycnogenol, and grape seed extract are additional antioxidants to consider. A recent study led by Dr. Grimes showed significant improvement in melasma with Malasezzin, a novel natural microbiome indole produced by Malassezia furfur. Superficial chemical peels and microneedling may be helpful adjunct treatment to topical therapies. In refractory cases of melasma, laser treatment with Q-switched (LFQS) Nd-YAG or fractional 1550/1540 nm non-ablative therapy may be considered.
Vitiligo is a psychologically devastating disease with significant impact on quality of life, and treatment also requires a multimodal approach. Stages of treatment are stabilization of active disease, repigmentation, and maintenance. Therapies for stabilization include oral mini-pulse (OMP) therapy with dexamethasone, methotrexate, minocycline, intramuscular triamcinolone, narrow band UVB phototherapy, and oral antioxidants. Vitamin D status should be assessed in vitiligo patients and supplemented in patients with deficiency. Topical calcineurin inhibitors have comparable response rates to topical corticosteroids and may be added to phototherapy for an enhanced response. Excimer laser in combination with topical therapy also showed high response rates. 311-nm Titanium:Sapphire laser showed similar efficacy to excimer laser in localized vitiligo. Afamelanotide is a synthetic analogue of a-MSH administered as an injectable implant which showed efficacy for vitiligo in recent studies. Other emerging therapies to look out for in vitiligo treatment include prostaglandin F2a analogues (latanoprost and bimatoprost) and topical ruxolitinib cream.
Medical Treatment of Actinic Keratosis and NMSC Neal Bhatia, MD, FAAD
We learned about current and upcoming treatment options for actinic keratoses (AK) and non-melanoma skin cancers (NMSC) from Dr. Bhatia’s exciting talk. The combination of topical calcipotriol with 5-fluorouracil or the use of short-contact topical calcipotriene foam with 5-fluorouracil after cryotherapy may result in improved long-term outcomes for actinic keratoses. Tirbanibulin is a new anti-proliferative and pro-apoptotic topical therapy that seems to be effective for actinic keratoses and induces less inflammation and tissue necrosis. Polypodium leucotomos extract (240mg) and nicotinamide (500mg) may help prevent UV-induced damage. In terms of PDT, treatment of actinic keratoses may be improved by combining PDT with microneedle pretreatment at a 20-minute ALA incubation time. Additionally, we may consider a simultaneous PDT regimen in which blue light is started immediately upon application of ALA, which is essentially painless with similar efficacy to conventional PDT. A promising new treatment for lesion-directed treatment of actinic keratoses is microwave therapy for non-ablative immune modulation.
Medical treatments for advanced NMSC include hedgehog pathway inhibitors and PD-1 inhibitors. Cemiplimab is a PD-1 inhibitor FDA approved for treatment of advanced cutaneous SCC, and more recently approved for locally advanced BCC or metastatic BCC previously treated with a hedgehog inhibitor or for whom a hedgehog inhibitor is not appropriate. In terms of hedgehog inhibitors, dermatologists should consider treating patients with these agents themselves instead of sending them to someone else. Vismodegib 150mg daily provided benefit to over 90% of patients. L-carnitine can be used prior to starting a hedgehog inhibitor to help with muscle cramps. Vismodegib may also be used to reduce tumor size prior to surgical treatment. To prevent late recurrences, patients may be offered a hedgehog inhibitor 10-15 days per month for 6-12 months. Other treatments for BCC and Gorlin’s syndrome that work via this pathway include itraconazole, and the newer Smoothened inhibitors taladegib (oral) and patidegib (topical).
IL-17 Inhibitors, IL-23 Inhibitors, and Precision Medicine in Psoriasis Jashin Wu, MD, FAAD
Dr. Jashin Wu reviewed updates in IL-17 inhibitors and IL-23 inhibitors. On June 1, 2021, secukinumab was approved for psoriasis patients 6 years and older with dosage based on body weight (less than 50 kg: 75mg; greater than or equal to 50 kg: 150mg) administered weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter.
Bimekizumab is a IL-17A/F inhibitor that should be approved by the FDA shortly. It is likely to be the most effective biologic for psoriasis when approved. There are head-to-head trials of bimekizumab vs secukinumab, bimekizumab vs ustekinumab, and bimekizumab vs adalimumab, with bimekizumab showing higher efficacy in these 3 clinical trials.
Guselkumab and tildrakizumab had recent publications showing 5-year data for efficacy and safety. Risankizumab was approved on January 21, 2022 for psoriatic arthritis.
Precision medicine in psoriasis is becoming a reality soon. Currently, there is no simple predictive tool to select appropriate initial treatment, and patients may not respond optimally. Mind.px is a painless, minimally invasive test to predict drug response to each biologic class. It has a 91% positive predictive value with a turnaround time of 14 days. Mind.Px from Mindera Health is currently available.
Poster of the Day
Efficacy and safety of tralokinumab in adolescents with moderate-to-severe atopic dermatitis: results of the phase 3 ECZTRA 6 trial
Tralokinumab is a fully human monoclonal antibody that neutralizes the cytokine interleukin 13 (IL-13), a key driver in the pathogenesis of atopic dermatitis (AD). In this study, the objective was to evaluate the efficacy and safety of tralokinumab in adolescents with moderate-to-severe atopic dermatitis in the phase 3 ECZTRA 6 trial. Patients included were age 12-17 with a history of AD ≥1 year, BSA ≥10%, EASI score ≥12, IGA score ≥3, and history of topical corticosteroid and /or topical calcineurin inhibitor treatment failure or for whom these treatments are medically inadvisable.
At Week 16, tralokinumab treatment was associated with greater achievement of IGA 0/1 and EASI-75 and improvement in adolescent pruritus NRS, change in SCORAD and change in CDLQI from baseline as compared to placebo. The majority of adverse events were mild or moderate in severity and comparable between the tralokinumab and placebo treatment groups.
In conclusion, tralokinumab 150mg and 300mg every 2 weeks demonstrated significant efficacy compared to placebo in adolescents with moderate-to-severe atopic dermatitis. Tralokinumab was well-tolerated in this study and results were comparable to those in phase 3 tralokinumab trials in adults.