New GI, topical approaches target rosacea

SAN FRANCISCO – Things are looking rosier for the treatment of rosacea, according to Dr. Kanade Shinkai.

"Two exciting new treatments" are likely to change clinical practices around this difficult-to-treat disease while researchers continue to gather more data on their use, she said at the annual meeting of the Pacific Dermatologic Association.

Dr. Shinkai said she was encouraged by preliminary data on treating rosacea indirectly by using off-label rifaximin for small intestinal bacterial overgrowth and by a new formulation of brimonidine approved in August as the first topical agent for the erythema of rosacea.

The GI approach looks promising enough to incorporate into her practice, said Dr. Shinkai of the University of California, San Francisco.

That strategy grew out of a 2008 study showing that 52 (46%) of 113 patients with rosacea had small intestinal bacterial overgrowth (SIBO) compared with 3 (5%) of 60 healthy matched controls. Treating SIBO with the antibiotic rifaximin (a cousin of rifampin) at 400 mg thrice daily for 10 days cleared rosacea in 35 (78%) of the 45 patients in whom SIBO was eradicated. Cleared rosacea remained clear for up to 9 months in 96% of patients. In two patients, both rosacea and SIBO recurred (Clin. Gastroenterol. Hepatol. 2008;6:759-64).

Investigators hypothesized that SIBO might modulate cytokines by increasing tumor necrosis factor–alpha, suppressing interleukin-17, or increasing the T helper cell type 1 pathway gene to drive skin inflammation. Mechanistically, the gut could be inducing molecular mimicry that results in extraintestinal disease due to these cytokine triggers, said Dr. Shinkai.

A more recent pilot study showed that 32 (51%) of 63 patients with rosacea had SIBO compared with 7 (23%) of 30 control subjects in the general population. Among 28 patients who took rifaximin for their SIBO, rosacea cleared in 46%, moderately improved in 25%, and mildly improved in 11%. No improvement was seen in 18% (J. Am. Acad. Dermatol. 2013;68:875-6).

"Rosacea can be very difficult to treat. This is at least one avenue that we can ask about," she said. Patients with rosacea who have more GI symptoms "will be the ones that I’ll target with rifaximin."

Most cases of rosacea in the study were confirmed by dermatologists. The studies used a positive lactulose/glucose breath test as a surrogate for diagnosing SIBO, a less-invasive strategy than the standard for diagnosis: jejunal aspirate. Larger double-blind studies that include jejunal aspirates probably will be needed "to really prove that this is a worthy treatment," Dr. Shinkai said.

The other addition to the regimen for rosacea is the new 0.33% topical brimonidine gel (Mirvaso), approved by the Food and Drug Administration in August 2013 for the treatment of the facial erythema of rosacea in adults. Each gram of gel contains 5 mg of brimonidine tartrate, equivalent to 3.3 mg of brimonidine free base, according to Galderma, which markets the drug.

"I think that’s a very important breakthrough considering what we tell patients now for erythema, which is to avoid their triggers (sun exposure, hot spicy foods, hot liquid) or to consider laser therapy, which is not an option for many patients because of the insurance issue," she said.

Brimonidine is a highly selective alpha₂-adrenergic agonist that is very vasoconstrictive. The drug has a known safety and efficacy profile from its long-term use as a treatment for glaucoma, but the topical gel is a new formulation.

Approval was based on two Galderma-funded pivotal trials of various doses of the gel in a total of 391 patients, which showed dose-dependent reductions in erythema for 12 hours and a two-grade improvement in erythema ratings by clinicians, patients, and Chroma Meter (Br. J. Dermatol. 2012;166:633-41).

The drug was fast acting and well tolerated, Dr. Shinkai said. Stopping the medication did cause a kind of tachyphylaxis seen with other alpha-adrenergics used to treat nasal or conjunctival congestion, where stopping the drug increased erythema or edema. Two patients in the studies developed mild, transient decreases in intraocular pressure, probably a result of inadvertently getting the gel in the eye, she said. Both studies were short, with 4 weeks of follow-up.

"I think the jury is still out" until more data become available on long-term use of brimonidine for erythema in rosacea. "However, I think this is a really exciting new development" because it adds to the few tools available for treatment, she said.

Dr. Shinkai reported having no relevant financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN FRANCISCO – Things are looking rosier for the treatment of rosacea, according to Dr. Kanade Shinkai.

"Two exciting new treatments" are likely to change clinical practices around this difficult-to-treat disease while researchers continue to gather more data on their use, she said at the annual meeting of the Pacific Dermatologic Association.

Dr. Shinkai said she was encouraged by preliminary data on treating rosacea indirectly by using off-label rifaximin for small intestinal bacterial overgrowth and by a new formulation of brimonidine approved in August as the first topical agent for the erythema of rosacea.

The GI approach looks promising enough to incorporate into her practice, said Dr. Shinkai of the University of California, San Francisco.

That strategy grew out of a 2008 study showing that 52 (46%) of 113 patients with rosacea had small intestinal bacterial overgrowth (SIBO) compared with 3 (5%) of 60 healthy matched controls. Treating SIBO with the antibiotic rifaximin (a cousin of rifampin) at 400 mg thrice daily for 10 days cleared rosacea in 35 (78%) of the 45 patients in whom SIBO was eradicated. Cleared rosacea remained clear for up to 9 months in 96% of patients. In two patients, both rosacea and SIBO recurred (Clin. Gastroenterol. Hepatol. 2008;6:759-64).

Investigators hypothesized that SIBO might modulate cytokines by increasing tumor necrosis factor–alpha, suppressing interleukin-17, or increasing the T helper cell type 1 pathway gene to drive skin inflammation. Mechanistically, the gut could be inducing molecular mimicry that results in extraintestinal disease due to these cytokine triggers, said Dr. Shinkai.

A more recent pilot study showed that 32 (51%) of 63 patients with rosacea had SIBO compared with 7 (23%) of 30 control subjects in the general population. Among 28 patients who took rifaximin for their SIBO, rosacea cleared in 46%, moderately improved in 25%, and mildly improved in 11%. No improvement was seen in 18% (J. Am. Acad. Dermatol. 2013;68:875-6).

"Rosacea can be very difficult to treat. This is at least one avenue that we can ask about," she said. Patients with rosacea who have more GI symptoms "will be the ones that I’ll target with rifaximin."

Most cases of rosacea in the study were confirmed by dermatologists. The studies used a positive lactulose/glucose breath test as a surrogate for diagnosing SIBO, a less-invasive strategy than the standard for diagnosis: jejunal aspirate. Larger double-blind studies that include jejunal aspirates probably will be needed "to really prove that this is a worthy treatment," Dr. Shinkai said.

The other addition to the regimen for rosacea is the new 0.33% topical brimonidine gel (Mirvaso), approved by the Food and Drug Administration in August 2013 for the treatment of the facial erythema of rosacea in adults. Each gram of gel contains 5 mg of brimonidine tartrate, equivalent to 3.3 mg of brimonidine free base, according to Galderma, which markets the drug.

"I think that’s a very important breakthrough considering what we tell patients now for erythema, which is to avoid their triggers (sun exposure, hot spicy foods, hot liquid) or to consider laser therapy, which is not an option for many patients because of the insurance issue," she said.

Brimonidine is a highly selective alpha₂-adrenergic agonist that is very vasoconstrictive. The drug has a known safety and efficacy profile from its long-term use as a treatment for glaucoma, but the topical gel is a new formulation.

Approval was based on two Galderma-funded pivotal trials of various doses of the gel in a total of 391 patients, which showed dose-dependent reductions in erythema for 12 hours and a two-grade improvement in erythema ratings by clinicians, patients, and Chroma Meter (Br. J. Dermatol. 2012;166:633-41).

The drug was fast acting and well tolerated, Dr. Shinkai said. Stopping the medication did cause a kind of tachyphylaxis seen with other alpha-adrenergics used to treat nasal or conjunctival congestion, where stopping the drug increased erythema or edema. Two patients in the studies developed mild, transient decreases in intraocular pressure, probably a result of inadvertently getting the gel in the eye, she said. Both studies were short, with 4 weeks of follow-up.

"I think the jury is still out" until more data become available on long-term use of brimonidine for erythema in rosacea. "However, I think this is a really exciting new development" because it adds to the few tools available for treatment, she said.

Dr. Shinkai reported having no relevant financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN FRANCISCO – Things are looking rosier for the treatment of rosacea, according to Dr. Kanade Shinkai.

"Two exciting new treatments" are likely to change clinical practices around this difficult-to-treat disease while researchers continue to gather more data on their use, she said at the annual meeting of the Pacific Dermatologic Association.

Dr. Shinkai said she was encouraged by preliminary data on treating rosacea indirectly by using off-label rifaximin for small intestinal bacterial overgrowth and by a new formulation of brimonidine approved in August as the first topical agent for the erythema of rosacea.

The GI approach looks promising enough to incorporate into her practice, said Dr. Shinkai of the University of California, San Francisco.

That strategy grew out of a 2008 study showing that 52 (46%) of 113 patients with rosacea had small intestinal bacterial overgrowth (SIBO) compared with 3 (5%) of 60 healthy matched controls. Treating SIBO with the antibiotic rifaximin (a cousin of rifampin) at 400 mg thrice daily for 10 days cleared rosacea in 35 (78%) of the 45 patients in whom SIBO was eradicated. Cleared rosacea remained clear for up to 9 months in 96% of patients. In two patients, both rosacea and SIBO recurred (Clin. Gastroenterol. Hepatol. 2008;6:759-64).

Investigators hypothesized that SIBO might modulate cytokines by increasing tumor necrosis factor–alpha, suppressing interleukin-17, or increasing the T helper cell type 1 pathway gene to drive skin inflammation. Mechanistically, the gut could be inducing molecular mimicry that results in extraintestinal disease due to these cytokine triggers, said Dr. Shinkai.

A more recent pilot study showed that 32 (51%) of 63 patients with rosacea had SIBO compared with 7 (23%) of 30 control subjects in the general population. Among 28 patients who took rifaximin for their SIBO, rosacea cleared in 46%, moderately improved in 25%, and mildly improved in 11%. No improvement was seen in 18% (J. Am. Acad. Dermatol. 2013;68:875-6).

"Rosacea can be very difficult to treat. This is at least one avenue that we can ask about," she said. Patients with rosacea who have more GI symptoms "will be the ones that I’ll target with rifaximin."

Most cases of rosacea in the study were confirmed by dermatologists. The studies used a positive lactulose/glucose breath test as a surrogate for diagnosing SIBO, a less-invasive strategy than the standard for diagnosis: jejunal aspirate. Larger double-blind studies that include jejunal aspirates probably will be needed "to really prove that this is a worthy treatment," Dr. Shinkai said.

The other addition to the regimen for rosacea is the new 0.33% topical brimonidine gel (Mirvaso), approved by the Food and Drug Administration in August 2013 for the treatment of the facial erythema of rosacea in adults. Each gram of gel contains 5 mg of brimonidine tartrate, equivalent to 3.3 mg of brimonidine free base, according to Galderma, which markets the drug.

"I think that’s a very important breakthrough considering what we tell patients now for erythema, which is to avoid their triggers (sun exposure, hot spicy foods, hot liquid) or to consider laser therapy, which is not an option for many patients because of the insurance issue," she said.

Brimonidine is a highly selective alpha₂-adrenergic agonist that is very vasoconstrictive. The drug has a known safety and efficacy profile from its long-term use as a treatment for glaucoma, but the topical gel is a new formulation.

Approval was based on two Galderma-funded pivotal trials of various doses of the gel in a total of 391 patients, which showed dose-dependent reductions in erythema for 12 hours and a two-grade improvement in erythema ratings by clinicians, patients, and Chroma Meter (Br. J. Dermatol. 2012;166:633-41).

The drug was fast acting and well tolerated, Dr. Shinkai said. Stopping the medication did cause a kind of tachyphylaxis seen with other alpha-adrenergics used to treat nasal or conjunctival congestion, where stopping the drug increased erythema or edema. Two patients in the studies developed mild, transient decreases in intraocular pressure, probably a result of inadvertently getting the gel in the eye, she said. Both studies were short, with 4 weeks of follow-up.

"I think the jury is still out" until more data become available on long-term use of brimonidine for erythema in rosacea. "However, I think this is a really exciting new development" because it adds to the few tools available for treatment, she said.

Dr. Shinkai reported having no relevant financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert