PracticeUpdate Conference Series World Congress of Dermatology 2019

Extracorporeal Photopheresis With 5-Aminolevulinic Acid Proves Safe in Early Pilot Study It may offer amore targeted approach to the treatment of chronic graft-versus-host disease. R eplacing 8-methoxypsoralen (MOP) with 5-aminolevulinic acid (ALA) among patients undergoing extracorporeal photopheresis (ECP) appears safe and may offer a more targeted approach to chronic graft-versus-host disease, according to a pilot study of 3 patients. “The mechanism of action of ECP is not well understood, but we know that it is very complex,” explained Eidi Christensen, MD, PhD, of St. Olav's University Hospital in Trondheim, Norway, during her presentation, which was attended by Elsevier’s PracticeUpdate . “8-MOP is a very powerful DNA crosslinked agent that activates DNA to induce apoptosis of T cells when exposed to [ultraviolet A] light. The monocytes are converted to dendritic-presenting cells, and they load the apoptotic T cells. These apoptotic T cell-loaded dendritic antigen- presenting cells modulate and regulate the immune system...to induce immunological tolerance.” Many patients require this expensive treatment on an ongoing basis for years, and several have only a partial response. In addition, 8-MOP binds to the DNA of both diseased and normal cells, with no selectivity in its killing effect, she continued. A potential alternative to 8-MOP is 5-ALA, is a precursor of protoporphyrin IX (PpIX), which is used in photodynamic therapy. “Photodynamic therapy is based on light activation of porphyrins,” said Dr. Christensen. “By action through light and the presence of oxygen, we have a photochemical reaction, which induces both necrosis and apoptosis of the T cells. We also get a mainly selected destruction of targeted cells [because of] selective production of PpIX, particularly in the proliferative, transformed, activated CD3+ T cells.” Dr. Christensen reported on 3 patients with chronic graft-versus-host disease who were included in the study because they were considered to respond inadequately to 8-MOP ECP. These patients underwent standard, approved, fully integrated photopheresis with ALA at a dose of 10 mM, instead of 8-MOP. Patients were treated with one cycle (two treatments on 2 consec- utive days) at various intervals for up to 10 cycles, with follow-ups at 3, 6, 9, and 12 months after treatment. To date, 44 treatments have been delivered. For each of the patients in the pilot study, safety tests conducted before and after treatments included blood pressure, heart rate, temperature, electrocardiogram, liver enzymes, and prothrombin time. Patients were also specifically asked at each follow-up session about the presence of vomiting, nausea, headache, evidence of photosensitivity, and chills. These were graded on a scale of 1 to 5. There were no significant changes before and after therapy. No serious adverse events have been reported. There have been episodes of tran- sient infection (colds and urinary tract infection) as well as vomiting, nausea, headache and chills. All reported side effects were grade 3 or lower. Manifestation of skin disease became less extensive during treatment. In a very preliminary plasma analysis, there was no evidence of PpIX, either before or at multiple time periods after testing. In conclusion, said Dr. Christensen, “we found that the patients tolerate this very well. No toxicity has been shown.”

“By blocking TrkA with a topical non-steroidal tissue targeted kinase inhibitor, we were able to not only reduce the symptoms of itch, burning and pain in a quite substantive and meaningful way, but were also able, via targeting what has traditionally been known as a neural/itch pathway, to impact the key inflammatory pathways associated with psoriasis, and in doing so improve the visible signs of the disease, the psoriatic plaque,” said Dr. Lizzul. Treatment with SNA-120 was generally safe and well tolerated; treatment-related adverse events were observed in only 2 patients and included dermatitis (in the 0.5% SNA-120 group) and pain and pruritus (in the vehicle control group). There were six serious adverse events spread among 3 subjects, but none of these were deemed treatment-related. “SNA-120 is formulated in an elegant emollient vehicle and has demonstrated a favorable safety profile to date, with no local tolerability issues, and can also be used in sensitive areas, such as skin folds, face, genitals and scalp,” Dr. Lizzul said. He concluded that the results of this trial “confirm what astute clinicians have noted for many years, that peripheral nerves play an important role in psoriasis. The data highlight the link between these clinical observations and the basic mechanisms and pathology underlying them.” Additional biopsy and biomarker data from this study will be presented in the fall. A pair of phase III studies will also begin later this year, pending approval from regulators.

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www.practiceupdate.com/c/85593

WCD 2019 • PRACTICEUPDATE CONFERENCE SERIES 15