The dietary supplement nicotinamide has been recommended by dermatologists for people with a history of skin cancer since 2015, when a clinical study with 386 participants showed that those who took the vitamin B3 derivative developed fewer new occurrences. 

However, data to validate those findings in a larger study group has been lacking because nicotinamide can be purchased over the counter without being entered into patients’ medical records.

In a new study published Sept. 17 in JAMA Dermatology, researchers found a way to get that data by analyzing records from the Veterans Affairs Corporate Data Warehouse. Nicotinamide is on the VA’s official formulary, so the researchers checked the outcomes of 33,833 patients for their next skin cancer diagnosis following baseline treatment with 500 milligrams of nicotinamide twice daily for longer than 30 days. They looked for occurrences of basal cell carcinoma and cutaneous squamous cell carcinoma. 

The researchers compared 12,287 patients who received the treatment with 21,479 who did not. Overall, there was a 14% reduction in skin cancer risk. When nicotinamide was taken after a first skin cancer, the risk reduction rose to 54%, but the benefit declined with treatment initiation following subsequent skin cancers. The risk reduction was much larger for squamous cell carcinoma.  

“There are no guidelines for when to start treatment with nicotinamide for skin cancer prevention in the general population. These results would really shift our practice from starting it once patients have developed numerous skin cancers to starting it earlier. We still need to do a better job of identifying who will actually benefit, as roughly only half of patients will develop multiple skin cancers,” said the study’s corresponding author, Lee Wheless, MD, PhD, assistant professor of Dermatology and Medicine at Vanderbilt University Medical Center and a staff physician at VA Tennessee Valley Healthcare System. 

The researchers were also able to ascertain the outcomes of 1,334 patients who were immunocompromised due to having received solid organ transplants. Among solid organ transplant recipients, no overall significant risk reduction was observed, although early nicotinamide use was associated with reduced occurrences of cutaneous squamous cell carcinoma. 

Wheless received research support from a Department of Veterans Affairs grant (IK2CX002452). Other Vanderbilt authors on the study are Katyln Knox, Rachel Weiss, Siwei Zhang, PhD, Lydia Yao, MS, Yaomin Xu, PhD, and Kyle Maas. 

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Some cancer patients experience durable remissions from immune checkpoint inhibitors that spur their T cells to attack cancer cells, but these immunotherapies can also cause reactions.

One of the adverse effects of these treatments is skin reactions known as cutaneous immune-related adverse events (cirAEs), although it is not known how often they morph into a chronic condition. Research led by investigators at Vanderbilt University Medical Center published in JAMA Dermatology provides insight into chronic cirAEs. They recommended long-term follow-up for patients by dermatologists familiar with cirAEs and consideration of corticosteroid-sparing treatment options.

“Understanding the potential for side effects to become long-lasting has been an important advance recently, and managing them more effectively is a key unmet need,” said the study’s corresponding author, Douglas Johnson, MD, MSCI, professor of Medicine, holder of the Susan and Luke Simons Directorship, and co-leader of the Translational Research and Interventional Oncology Research Program at Vanderbilt-Ingram Cancer Center.

The investigators reviewed the records of 318 patients from a previous study who had been treated with immune checkpoint inhibitors. Of that number, 100 or 31% developed cirAEs with the skin conditions becoming chronic for 24 of the patients — nearly 8% of the full cohort. The study looked at 21 of those patients who underwent detailed follow-up. Another 31 patients were added from Vanderbilt clinics who were treated for cirAEs.

The 52 patients had received either pembrolizumab, nivolumab, ipilimumab or anti-PD1 and CTLA4 combination therapy.

The types of skin reactions varied, with 15 experiencing pruritus or itchy skin, 12 experienced morbilliform eruptions or drug-induced skin rashes, 12 experienced dermatitis or inflamed and scaly rashes, eight experienced bullous pemphigoid-like eruptions (fluid-filled blisters that resemble a rare autoimmune skin disease), five experienced eczema, four experienced lichenoid (flat-topped, scaly lesions), two experienced psoriasiform (breakouts that resemble psoriasis), and one experienced acneiform or acne-like eruptions.

The median duration of cirAE from treatment cessation was 446 days. Rare cases lasted more than five years.

Other Vanderbilt authors on the study included the study’s lead author, Kylie Fletcher, BS, Rachel Goodman, MD, MBA, J. Randall Patrinely, MD, MBA, and Anna Dewan, MD, MHS.

The research received support from Medical Scholars at Vanderbilt University School of Medicine, the Susan and Luke Simons Directorship, the James C. Bradford Jr. Fund in Melanoma Cancer Research and the Van Stephenson Memorial Cancer Research Fund.

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