Bruce Jancin

WAIKOLOA, HAWAII – Patient interest is soaring in fat cell reduction via cryolipolysis using the noninvasive CoolSculpting technology, Dr. Suzanne L. Kilmer said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

She was one of the developers of the “treatment to transformation” (T2T) approach to CoolSculpting, in which larger areas of fat deposits are safely treated per session than in the earliest days of the therapy’s availability.

Frontline Medical News/Bruce Jancin

“Treatment to transformation has been a home run. Our use of this approach has increased greatly in our practice because a lot of people don’t want to do liposuction, which has more risk and downtime. We’ve purchased a second device to accommodate patients and treat two areas at once, said Dr. Kilmer, director of the Laser and Skin Surgery Center of Northern California in Sacramento.

She was lead author of the pivotal trial which led to Food and Drug Administration clearance of Zeltiq Aesthetics’ CoolSculpting for treatment of submental fat. That’s the fifth body area for which FDA clearance has been obtained on the basis of solid evidence of safety and efficacy, the others being the inner thighs, outer thighs, flanks or love handles, and abdomen.

The pivotal trial included 60 patients who underwent CoolSculpting for a double chin, or submental fullness, using a prototype of the device known as the CoolMini submental applicator, a small-volume vacuum delivery cup. The patient’s double chin was placed in the applicator, then a 60-minute–long treatment cycle was delivered to that area at –10° C. An optional second treatment could be delivered 6 weeks later.

There were no procedure-related serious adverse events. Ultrasound assessment carried out 12 weeks after the final cryolipolysis treatment showed a mean 2-mm reduction in fat layer thickness. Eighty-three percent of patients declared themselves satisfied, 77% reported visible fat reduction, 77% reported that they felt their appearance had improved, 76% found the procedure comfortable, and 80% indicated they would recommend submental cryolipolysis to a friend (Lasers Surg Med. 2016 Jan;48[1]:3-13).

Dr. Kilmer noted that cryolipolysis has been cleared by the FDA for fat reduction since 2010. It works by inducing a delayed slow death of fat cells via apoptosis. There is no immediate effect and the noninvasive procedure involves no anesthetics. There is very little inflammation, discomfort, or downtime for recovery. The typical result is roughly a 20% loss in fat cells in treated areas.

She offered a couple of practical tips regarding cryolipolysis for reduction of submental fat. First, the entire targeted area of submental fat must be able to fit inside the applicator. And after successful cryolipolysis, any residual areas of fat cells will have to be targeted using injections of deoxycholic acid (Kybella), because a small pocket of submental fat won’t get sucked up into the CoolMini applicator. (Deoxycholic acid was approved by the FDA in 2015, for treating moderate to severe submental fat in adults.)

“Actually, we use both treatments together on most people. When they have a lot of fat we start out by killing it with cryolipolysis. Then when it gets smaller we trim it down with deoxycholic acid, often with a neuromodulator to deal with the platysmal bands,” Dr. Kilmer said.

She reported serving on medical advisory boards for Zeltiq and a handful of other dermatologic device companies and receiving research funding from half a dozen companies.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Patient interest is soaring in fat cell reduction via cryolipolysis using the noninvasive CoolSculpting technology, Dr. Suzanne L. Kilmer said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

She was one of the developers of the “treatment to transformation” (T2T) approach to CoolSculpting, in which larger areas of fat deposits are safely treated per session than in the earliest days of the therapy’s availability.

Frontline Medical News/Bruce Jancin

“Treatment to transformation has been a home run. Our use of this approach has increased greatly in our practice because a lot of people don’t want to do liposuction, which has more risk and downtime. We’ve purchased a second device to accommodate patients and treat two areas at once, said Dr. Kilmer, director of the Laser and Skin Surgery Center of Northern California in Sacramento.

She was lead author of the pivotal trial which led to Food and Drug Administration clearance of Zeltiq Aesthetics’ CoolSculpting for treatment of submental fat. That’s the fifth body area for which FDA clearance has been obtained on the basis of solid evidence of safety and efficacy, the others being the inner thighs, outer thighs, flanks or love handles, and abdomen.

The pivotal trial included 60 patients who underwent CoolSculpting for a double chin, or submental fullness, using a prototype of the device known as the CoolMini submental applicator, a small-volume vacuum delivery cup. The patient’s double chin was placed in the applicator, then a 60-minute–long treatment cycle was delivered to that area at –10° C. An optional second treatment could be delivered 6 weeks later.

There were no procedure-related serious adverse events. Ultrasound assessment carried out 12 weeks after the final cryolipolysis treatment showed a mean 2-mm reduction in fat layer thickness. Eighty-three percent of patients declared themselves satisfied, 77% reported visible fat reduction, 77% reported that they felt their appearance had improved, 76% found the procedure comfortable, and 80% indicated they would recommend submental cryolipolysis to a friend (Lasers Surg Med. 2016 Jan;48[1]:3-13).

Dr. Kilmer noted that cryolipolysis has been cleared by the FDA for fat reduction since 2010. It works by inducing a delayed slow death of fat cells via apoptosis. There is no immediate effect and the noninvasive procedure involves no anesthetics. There is very little inflammation, discomfort, or downtime for recovery. The typical result is roughly a 20% loss in fat cells in treated areas.

She offered a couple of practical tips regarding cryolipolysis for reduction of submental fat. First, the entire targeted area of submental fat must be able to fit inside the applicator. And after successful cryolipolysis, any residual areas of fat cells will have to be targeted using injections of deoxycholic acid (Kybella), because a small pocket of submental fat won’t get sucked up into the CoolMini applicator. (Deoxycholic acid was approved by the FDA in 2015, for treating moderate to severe submental fat in adults.)

“Actually, we use both treatments together on most people. When they have a lot of fat we start out by killing it with cryolipolysis. Then when it gets smaller we trim it down with deoxycholic acid, often with a neuromodulator to deal with the platysmal bands,” Dr. Kilmer said.

She reported serving on medical advisory boards for Zeltiq and a handful of other dermatologic device companies and receiving research funding from half a dozen companies.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Patient interest is soaring in fat cell reduction via cryolipolysis using the noninvasive CoolSculpting technology, Dr. Suzanne L. Kilmer said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

She was one of the developers of the “treatment to transformation” (T2T) approach to CoolSculpting, in which larger areas of fat deposits are safely treated per session than in the earliest days of the therapy’s availability.

Frontline Medical News/Bruce Jancin

“Treatment to transformation has been a home run. Our use of this approach has increased greatly in our practice because a lot of people don’t want to do liposuction, which has more risk and downtime. We’ve purchased a second device to accommodate patients and treat two areas at once, said Dr. Kilmer, director of the Laser and Skin Surgery Center of Northern California in Sacramento.

She was lead author of the pivotal trial which led to Food and Drug Administration clearance of Zeltiq Aesthetics’ CoolSculpting for treatment of submental fat. That’s the fifth body area for which FDA clearance has been obtained on the basis of solid evidence of safety and efficacy, the others being the inner thighs, outer thighs, flanks or love handles, and abdomen.

The pivotal trial included 60 patients who underwent CoolSculpting for a double chin, or submental fullness, using a prototype of the device known as the CoolMini submental applicator, a small-volume vacuum delivery cup. The patient’s double chin was placed in the applicator, then a 60-minute–long treatment cycle was delivered to that area at –10° C. An optional second treatment could be delivered 6 weeks later.

There were no procedure-related serious adverse events. Ultrasound assessment carried out 12 weeks after the final cryolipolysis treatment showed a mean 2-mm reduction in fat layer thickness. Eighty-three percent of patients declared themselves satisfied, 77% reported visible fat reduction, 77% reported that they felt their appearance had improved, 76% found the procedure comfortable, and 80% indicated they would recommend submental cryolipolysis to a friend (Lasers Surg Med. 2016 Jan;48[1]:3-13).

Dr. Kilmer noted that cryolipolysis has been cleared by the FDA for fat reduction since 2010. It works by inducing a delayed slow death of fat cells via apoptosis. There is no immediate effect and the noninvasive procedure involves no anesthetics. There is very little inflammation, discomfort, or downtime for recovery. The typical result is roughly a 20% loss in fat cells in treated areas.

She offered a couple of practical tips regarding cryolipolysis for reduction of submental fat. First, the entire targeted area of submental fat must be able to fit inside the applicator. And after successful cryolipolysis, any residual areas of fat cells will have to be targeted using injections of deoxycholic acid (Kybella), because a small pocket of submental fat won’t get sucked up into the CoolMini applicator. (Deoxycholic acid was approved by the FDA in 2015, for treating moderate to severe submental fat in adults.)

“Actually, we use both treatments together on most people. When they have a lot of fat we start out by killing it with cryolipolysis. Then when it gets smaller we trim it down with deoxycholic acid, often with a neuromodulator to deal with the platysmal bands,” Dr. Kilmer said.

She reported serving on medical advisory boards for Zeltiq and a handful of other dermatologic device companies and receiving research funding from half a dozen companies.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Generations of master clinicians in dermatology have made a practice of accumulating personal collections of obscure, non–evidence-based therapies for use when standard treatments aren’t getting the job done for challenging conditions.

Sometimes these dermatologic masters share them, as in the ‘what to do when you don’t know what to do’ compendium in Shelley and Shelley’s classic textbook, Advanced Dermatologic Therapeutics.

Bruce Jancin/Frontline Medical News

At the Hawaii Dermatology Seminar, Dr. Robert Sidbury opened his own little black book and shared several such backup pediatric dermatology therapies. All are off label. Their mechanisms of benefit are unclear. Formal supporting evidence is sparse to none. Some are time-honored therapies; indeed, one is a variant of Vleminckx’s solution, a popular treatment for severe nodulocystic acne in 1880. But these are all treatments Dr. Sidbury has personally found to be successful on repeated occasions as second-, third-, and fourth-line therapies, and he said he knows of other pediatric dermatologists with similarly favorable experiences using these agents.

“These just might be something to reach for when you’re out of options otherwise,” he explained at the seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“The gist of this talk is to help you realize what a gold mine your own experience and judgment is in trying to treat patients whose condition is stubborn. Sometimes we have a natural resistance to wanting to try things such as we’re talking about here, where there isn’t any supporting evidence. But if you can wrap your mind around the safety – if you’re comfortable with that – then I would encourage you to be more adventuresome,” said Dr. Sidbury, chief of dermatology at Seattle Children’s Hospital.

Among his go-to, last-resort recommendations are the following:

Griseofulvin for cutaneous or oral lichen planus. “I use tinea dosing: 20 mg/day in two divided doses, up to a maximum of 500-1,000 mg/day. I tend to give it for 1-2 months. I don’t follow labs when using griseofulvin for tinea or lichen planus,” he said.

This treatment is cited in the Shelleys’ textbook as well as in a recent systematic review and meta-analysis (Am J Clin Dermatol. 2016 Feb;17[1]:11-22).

Ketotifen for intractable itching. Dr. Sidbury calls pruritus of this severity “rogue itching,” which is not uncommon in patients with plexiform neurofibromas, very large keloids, or epidermolysis bullosa. “I’ve found ketotifen to be incredibly helpful when absolutely nothing else seems to help,” he said.

Ketotifen, an oral antihistamine, is a histamine-1 blocker and mast cell stabilizer. It’s not approved by the Food and Drug Administration but is available from Canada. Dr. Sidbury said he has found Northwest Pharmacy easy to work with online. The cost through that online pharmacy is $52 per 250 mL.

The oral dosing is 0.05 mg/kg twice a day in children aged 6 months up to 3 years, and 1 mg twice a day in children aged 3 years and older. He and others have found ketotifen to be extremely safe. Side effects are uncommon and consist of minimal sleep disruption, irritability, flulike symptoms, and weight gain.

Topical tofacitinib for alopecia areata. Tofacitinib (Xeljanz) is an oral Janus kinase inhibitor (JAK) approved for the treatment of rheumatoid arthritis. Dr. Sidbury has a compounding pharmacy make topical tofacitinib 2% in a liposomal base, which achieves better penetration than Versabase. He recommends Chemistry Rx in Philadelphia for compounding.

“I have no financial interest, I’ve just found them incredibly helpful. The cost is $330 for 30 g. That’s not dirt cheap by a long shot, but I’ve looked into this for parents before I was aware of the Chemistry Rx option, and the cost was thousands and thousands of dollars when I tried to get it compounded in a local pharmacy that didn’t have the economy of scale,” he said.

Patients apply the topical JAK inhibitor twice daily. “I’ve probably got six or seven kids on topical JAK inhibitor therapy for alopecia areata, and I’ve seen responses in all of them after having pretty much exhausted everything else,” according to the dermatologist.

He said he obtains a baseline CBC, liver enzyme levels, serum creatinine, and lipid levels, repeating the lab tests every 2 weeks initially, then monthly.

Vleminckx’s solution. This is a truly old school therapy for severe nodulocystic acne when isotretinoin isn’t an option. True Vleminckx’s solution is a sulfurated lime solution that smells terrible and is hard to come by. The closest thing Dr. Sidbury has found without resort to a compounding pharmacy is available OTC on Amazon. Thankfully, it contains an odor-masking agent, he said. He has patients apply the solution twice daily for 20 minutes at a time every other day.

Tar for vitiligo and lichen sclerosis. Vitiligo is a condition with a long list of treatment options, many of which aren’t all that effective. Dr. Sidbury learned of V-tar for vitiligo from Dr. Peter Lio, a pediatric dermatologist at Northwestern University, Chicago, who prescribes it frequently for stubborn areas, such as the knees and ankles. V-tar is a 30% crude coal tar product that’s water soluble. Patients apply a small amount once per week, and wash it off after 6-8 hours. V-tar is available from Dermasave Labs, a compounding pharmacy in Pleasant Valley, N.Y., he said.

For cases of lichen sclerosus where potent topical corticosteroids and topical calcineurin inhibitors are ineffective, he turns to twice-daily 6% liquor carbonis detergens in Aquaphor. It has an excellent safety profile. Irritation is rare and can be prevented using a barrier cream.

Fluconazole for erythema annulare centrifugum. Dr. Sidbury has used this on multiple occasions when standard therapy with antihistamines, topical steroids, topical calcineurin inhibitors, and/or calcipotriene didn’t work. At 3-6 mg/kg per day for 4 weeks, and a maximum daily dose of fluconazole of 200 mg, he has typically obtained a rapid reduction in itching, and skin clearance in about a week, with a sustained benefit.

This is another off-label treatment with a good safety profile, which he also frequently uses on label for neonates with candidiasis, Dr. Sidbury noted.

He reported having no financial conflicts regarding any of these therapies. SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Generations of master clinicians in dermatology have made a practice of accumulating personal collections of obscure, non–evidence-based therapies for use when standard treatments aren’t getting the job done for challenging conditions.

Sometimes these dermatologic masters share them, as in the ‘what to do when you don’t know what to do’ compendium in Shelley and Shelley’s classic textbook, Advanced Dermatologic Therapeutics.

Bruce Jancin/Frontline Medical News

At the Hawaii Dermatology Seminar, Dr. Robert Sidbury opened his own little black book and shared several such backup pediatric dermatology therapies. All are off label. Their mechanisms of benefit are unclear. Formal supporting evidence is sparse to none. Some are time-honored therapies; indeed, one is a variant of Vleminckx’s solution, a popular treatment for severe nodulocystic acne in 1880. But these are all treatments Dr. Sidbury has personally found to be successful on repeated occasions as second-, third-, and fourth-line therapies, and he said he knows of other pediatric dermatologists with similarly favorable experiences using these agents.

“These just might be something to reach for when you’re out of options otherwise,” he explained at the seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“The gist of this talk is to help you realize what a gold mine your own experience and judgment is in trying to treat patients whose condition is stubborn. Sometimes we have a natural resistance to wanting to try things such as we’re talking about here, where there isn’t any supporting evidence. But if you can wrap your mind around the safety – if you’re comfortable with that – then I would encourage you to be more adventuresome,” said Dr. Sidbury, chief of dermatology at Seattle Children’s Hospital.

Among his go-to, last-resort recommendations are the following:

Griseofulvin for cutaneous or oral lichen planus. “I use tinea dosing: 20 mg/day in two divided doses, up to a maximum of 500-1,000 mg/day. I tend to give it for 1-2 months. I don’t follow labs when using griseofulvin for tinea or lichen planus,” he said.

This treatment is cited in the Shelleys’ textbook as well as in a recent systematic review and meta-analysis (Am J Clin Dermatol. 2016 Feb;17[1]:11-22).

Ketotifen for intractable itching. Dr. Sidbury calls pruritus of this severity “rogue itching,” which is not uncommon in patients with plexiform neurofibromas, very large keloids, or epidermolysis bullosa. “I’ve found ketotifen to be incredibly helpful when absolutely nothing else seems to help,” he said.

Ketotifen, an oral antihistamine, is a histamine-1 blocker and mast cell stabilizer. It’s not approved by the Food and Drug Administration but is available from Canada. Dr. Sidbury said he has found Northwest Pharmacy easy to work with online. The cost through that online pharmacy is $52 per 250 mL.

The oral dosing is 0.05 mg/kg twice a day in children aged 6 months up to 3 years, and 1 mg twice a day in children aged 3 years and older. He and others have found ketotifen to be extremely safe. Side effects are uncommon and consist of minimal sleep disruption, irritability, flulike symptoms, and weight gain.

Topical tofacitinib for alopecia areata. Tofacitinib (Xeljanz) is an oral Janus kinase inhibitor (JAK) approved for the treatment of rheumatoid arthritis. Dr. Sidbury has a compounding pharmacy make topical tofacitinib 2% in a liposomal base, which achieves better penetration than Versabase. He recommends Chemistry Rx in Philadelphia for compounding.

“I have no financial interest, I’ve just found them incredibly helpful. The cost is $330 for 30 g. That’s not dirt cheap by a long shot, but I’ve looked into this for parents before I was aware of the Chemistry Rx option, and the cost was thousands and thousands of dollars when I tried to get it compounded in a local pharmacy that didn’t have the economy of scale,” he said.

Patients apply the topical JAK inhibitor twice daily. “I’ve probably got six or seven kids on topical JAK inhibitor therapy for alopecia areata, and I’ve seen responses in all of them after having pretty much exhausted everything else,” according to the dermatologist.

He said he obtains a baseline CBC, liver enzyme levels, serum creatinine, and lipid levels, repeating the lab tests every 2 weeks initially, then monthly.

Vleminckx’s solution. This is a truly old school therapy for severe nodulocystic acne when isotretinoin isn’t an option. True Vleminckx’s solution is a sulfurated lime solution that smells terrible and is hard to come by. The closest thing Dr. Sidbury has found without resort to a compounding pharmacy is available OTC on Amazon. Thankfully, it contains an odor-masking agent, he said. He has patients apply the solution twice daily for 20 minutes at a time every other day.

Tar for vitiligo and lichen sclerosis. Vitiligo is a condition with a long list of treatment options, many of which aren’t all that effective. Dr. Sidbury learned of V-tar for vitiligo from Dr. Peter Lio, a pediatric dermatologist at Northwestern University, Chicago, who prescribes it frequently for stubborn areas, such as the knees and ankles. V-tar is a 30% crude coal tar product that’s water soluble. Patients apply a small amount once per week, and wash it off after 6-8 hours. V-tar is available from Dermasave Labs, a compounding pharmacy in Pleasant Valley, N.Y., he said.

For cases of lichen sclerosus where potent topical corticosteroids and topical calcineurin inhibitors are ineffective, he turns to twice-daily 6% liquor carbonis detergens in Aquaphor. It has an excellent safety profile. Irritation is rare and can be prevented using a barrier cream.

Fluconazole for erythema annulare centrifugum. Dr. Sidbury has used this on multiple occasions when standard therapy with antihistamines, topical steroids, topical calcineurin inhibitors, and/or calcipotriene didn’t work. At 3-6 mg/kg per day for 4 weeks, and a maximum daily dose of fluconazole of 200 mg, he has typically obtained a rapid reduction in itching, and skin clearance in about a week, with a sustained benefit.

This is another off-label treatment with a good safety profile, which he also frequently uses on label for neonates with candidiasis, Dr. Sidbury noted.

He reported having no financial conflicts regarding any of these therapies. SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Generations of master clinicians in dermatology have made a practice of accumulating personal collections of obscure, non–evidence-based therapies for use when standard treatments aren’t getting the job done for challenging conditions.

Sometimes these dermatologic masters share them, as in the ‘what to do when you don’t know what to do’ compendium in Shelley and Shelley’s classic textbook, Advanced Dermatologic Therapeutics.

Bruce Jancin/Frontline Medical News

At the Hawaii Dermatology Seminar, Dr. Robert Sidbury opened his own little black book and shared several such backup pediatric dermatology therapies. All are off label. Their mechanisms of benefit are unclear. Formal supporting evidence is sparse to none. Some are time-honored therapies; indeed, one is a variant of Vleminckx’s solution, a popular treatment for severe nodulocystic acne in 1880. But these are all treatments Dr. Sidbury has personally found to be successful on repeated occasions as second-, third-, and fourth-line therapies, and he said he knows of other pediatric dermatologists with similarly favorable experiences using these agents.

“These just might be something to reach for when you’re out of options otherwise,” he explained at the seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“The gist of this talk is to help you realize what a gold mine your own experience and judgment is in trying to treat patients whose condition is stubborn. Sometimes we have a natural resistance to wanting to try things such as we’re talking about here, where there isn’t any supporting evidence. But if you can wrap your mind around the safety – if you’re comfortable with that – then I would encourage you to be more adventuresome,” said Dr. Sidbury, chief of dermatology at Seattle Children’s Hospital.

Among his go-to, last-resort recommendations are the following:

Griseofulvin for cutaneous or oral lichen planus. “I use tinea dosing: 20 mg/day in two divided doses, up to a maximum of 500-1,000 mg/day. I tend to give it for 1-2 months. I don’t follow labs when using griseofulvin for tinea or lichen planus,” he said.

This treatment is cited in the Shelleys’ textbook as well as in a recent systematic review and meta-analysis (Am J Clin Dermatol. 2016 Feb;17[1]:11-22).

Ketotifen for intractable itching. Dr. Sidbury calls pruritus of this severity “rogue itching,” which is not uncommon in patients with plexiform neurofibromas, very large keloids, or epidermolysis bullosa. “I’ve found ketotifen to be incredibly helpful when absolutely nothing else seems to help,” he said.

Ketotifen, an oral antihistamine, is a histamine-1 blocker and mast cell stabilizer. It’s not approved by the Food and Drug Administration but is available from Canada. Dr. Sidbury said he has found Northwest Pharmacy easy to work with online. The cost through that online pharmacy is $52 per 250 mL.

The oral dosing is 0.05 mg/kg twice a day in children aged 6 months up to 3 years, and 1 mg twice a day in children aged 3 years and older. He and others have found ketotifen to be extremely safe. Side effects are uncommon and consist of minimal sleep disruption, irritability, flulike symptoms, and weight gain.

Topical tofacitinib for alopecia areata. Tofacitinib (Xeljanz) is an oral Janus kinase inhibitor (JAK) approved for the treatment of rheumatoid arthritis. Dr. Sidbury has a compounding pharmacy make topical tofacitinib 2% in a liposomal base, which achieves better penetration than Versabase. He recommends Chemistry Rx in Philadelphia for compounding.

“I have no financial interest, I’ve just found them incredibly helpful. The cost is $330 for 30 g. That’s not dirt cheap by a long shot, but I’ve looked into this for parents before I was aware of the Chemistry Rx option, and the cost was thousands and thousands of dollars when I tried to get it compounded in a local pharmacy that didn’t have the economy of scale,” he said.

Patients apply the topical JAK inhibitor twice daily. “I’ve probably got six or seven kids on topical JAK inhibitor therapy for alopecia areata, and I’ve seen responses in all of them after having pretty much exhausted everything else,” according to the dermatologist.

He said he obtains a baseline CBC, liver enzyme levels, serum creatinine, and lipid levels, repeating the lab tests every 2 weeks initially, then monthly.

Vleminckx’s solution. This is a truly old school therapy for severe nodulocystic acne when isotretinoin isn’t an option. True Vleminckx’s solution is a sulfurated lime solution that smells terrible and is hard to come by. The closest thing Dr. Sidbury has found without resort to a compounding pharmacy is available OTC on Amazon. Thankfully, it contains an odor-masking agent, he said. He has patients apply the solution twice daily for 20 minutes at a time every other day.

Tar for vitiligo and lichen sclerosis. Vitiligo is a condition with a long list of treatment options, many of which aren’t all that effective. Dr. Sidbury learned of V-tar for vitiligo from Dr. Peter Lio, a pediatric dermatologist at Northwestern University, Chicago, who prescribes it frequently for stubborn areas, such as the knees and ankles. V-tar is a 30% crude coal tar product that’s water soluble. Patients apply a small amount once per week, and wash it off after 6-8 hours. V-tar is available from Dermasave Labs, a compounding pharmacy in Pleasant Valley, N.Y., he said.

For cases of lichen sclerosus where potent topical corticosteroids and topical calcineurin inhibitors are ineffective, he turns to twice-daily 6% liquor carbonis detergens in Aquaphor. It has an excellent safety profile. Irritation is rare and can be prevented using a barrier cream.

Fluconazole for erythema annulare centrifugum. Dr. Sidbury has used this on multiple occasions when standard therapy with antihistamines, topical steroids, topical calcineurin inhibitors, and/or calcipotriene didn’t work. At 3-6 mg/kg per day for 4 weeks, and a maximum daily dose of fluconazole of 200 mg, he has typically obtained a rapid reduction in itching, and skin clearance in about a week, with a sustained benefit.

This is another off-label treatment with a good safety profile, which he also frequently uses on label for neonates with candidiasis, Dr. Sidbury noted.

He reported having no financial conflicts regarding any of these therapies. SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

SAN DIEGO – Endometrial cancer patients who regularly took low-dose aspirin experienced markedly better 5-year disease-free and overall survival compared to nonusers in an observational study, Dr. Koji Matsuo reported at the annual meeting of the Society of Gynecologic Oncology.

This apparent survival-prolonging effect of aspirin was greatest in women who were obese, less than 60 years old, had type 1 endometrial cancer, and/or received postoperative whole pelvic radiotherapy. In fact, the benefits achieved statistical significance only in patients who fit into one or more of these subgroups, added Dr. Matsuo of the University of Southern California, Los Angeles.

Bruce Jancin/Frontline Medical News

He presented a multicenter retrospective study of 1,687 patients with surgically staged endometrial cancer, 158 of whom were regular users of low-dose aspirin for various reasons, mainly cardioprotection.

The 5-year disease-free survival rates in aspirin users and nonusers were 90.6% and 80.9%, respectively. The 5-year overall survival rates were 96.4%, compared with 87.3%. Aspirin users had a higher cardiovascular risk profile. Their mean BMI was 36.7 kg/m², versus 29.6 kg/m² for nonusers. Moreover, aspirin users were also significantly more likely to have hypertension, diabetes, and hypercholesterolemia, and to be taking medications to manage those conditions.

In a multivariate analysis controlled for age, ethnicity, obesity, medications, tumor grade, stage, and histology, as well as the use of postoperative radiation therapy or chemotherapy, the adjusted 5-year risk of disease progression was 54% lower among aspirin users than in nonusers. The risk of all-cause mortality was reduced by 77%, according to Dr. Matsuo.

Aspirin’s mechanism of anti-oncogenic benefit in the setting of endometrial cancer is believed to involve its ability to inhibit COX-2, thereby curbing the chronic inflammation that figures prominently in the disease. Dr. Matsuo called attention to a recent retrospective cohort study by investigators at Montefiore Medical Center in New York. In that study, concomitant use of aspirin and a statin by endometrial cancer patients was associated with a robust 75% reduction in the risk of cancer-specific mortality, compared with women on neither (Obstet Gynecol. 2015 Jul;126[1]:144-50).

Bruce Jancin/Frontline Medical News

On the separate issue of whether aspirin is also useful for prevention of endometrial cancer, Dr. Matsuo noted that a recent Danish meta-analysis demonstrated a significantly reduced risk of developing the malignancy in regular users of aspirin, particularly if obese. The relative risk reduction in obese aspirin users, compared with nonusers, amounted to 44% in case-control studies and 20% in cohort studies (Gynecol Oncol. 2016 Feb;140[2]:352-8).

Discussant Dr. Kala Visvanathan commented that while the usual caveats about nonrandomized studies such as Dr. Matsuo’s apply – they must be considered hypothesis-generating rather than definitive because of the possibility of unrecognized confounders – repurposing an old drug such as aspirin as a treatment for cancer has enormous appeal.

The safety profiles and drug interactions of older medications such as aspirin, statins, and metformin are well established. And the ability to use an inexpensive older drug to simultaneously prevent or treat multiple common and serious diseases is a tantalizing prospect, observed Dr. Visvanathan, professor of epidemiology and oncology at Johns Hopkins University, Baltimore.

bjancin@frontlinemedcom.com

SAN DIEGO – Endometrial cancer patients who regularly took low-dose aspirin experienced markedly better 5-year disease-free and overall survival compared to nonusers in an observational study, Dr. Koji Matsuo reported at the annual meeting of the Society of Gynecologic Oncology.

This apparent survival-prolonging effect of aspirin was greatest in women who were obese, less than 60 years old, had type 1 endometrial cancer, and/or received postoperative whole pelvic radiotherapy. In fact, the benefits achieved statistical significance only in patients who fit into one or more of these subgroups, added Dr. Matsuo of the University of Southern California, Los Angeles.

Bruce Jancin/Frontline Medical News

He presented a multicenter retrospective study of 1,687 patients with surgically staged endometrial cancer, 158 of whom were regular users of low-dose aspirin for various reasons, mainly cardioprotection.

The 5-year disease-free survival rates in aspirin users and nonusers were 90.6% and 80.9%, respectively. The 5-year overall survival rates were 96.4%, compared with 87.3%. Aspirin users had a higher cardiovascular risk profile. Their mean BMI was 36.7 kg/m², versus 29.6 kg/m² for nonusers. Moreover, aspirin users were also significantly more likely to have hypertension, diabetes, and hypercholesterolemia, and to be taking medications to manage those conditions.

In a multivariate analysis controlled for age, ethnicity, obesity, medications, tumor grade, stage, and histology, as well as the use of postoperative radiation therapy or chemotherapy, the adjusted 5-year risk of disease progression was 54% lower among aspirin users than in nonusers. The risk of all-cause mortality was reduced by 77%, according to Dr. Matsuo.

Aspirin’s mechanism of anti-oncogenic benefit in the setting of endometrial cancer is believed to involve its ability to inhibit COX-2, thereby curbing the chronic inflammation that figures prominently in the disease. Dr. Matsuo called attention to a recent retrospective cohort study by investigators at Montefiore Medical Center in New York. In that study, concomitant use of aspirin and a statin by endometrial cancer patients was associated with a robust 75% reduction in the risk of cancer-specific mortality, compared with women on neither (Obstet Gynecol. 2015 Jul;126[1]:144-50).

Bruce Jancin/Frontline Medical News

On the separate issue of whether aspirin is also useful for prevention of endometrial cancer, Dr. Matsuo noted that a recent Danish meta-analysis demonstrated a significantly reduced risk of developing the malignancy in regular users of aspirin, particularly if obese. The relative risk reduction in obese aspirin users, compared with nonusers, amounted to 44% in case-control studies and 20% in cohort studies (Gynecol Oncol. 2016 Feb;140[2]:352-8).

Discussant Dr. Kala Visvanathan commented that while the usual caveats about nonrandomized studies such as Dr. Matsuo’s apply – they must be considered hypothesis-generating rather than definitive because of the possibility of unrecognized confounders – repurposing an old drug such as aspirin as a treatment for cancer has enormous appeal.

The safety profiles and drug interactions of older medications such as aspirin, statins, and metformin are well established. And the ability to use an inexpensive older drug to simultaneously prevent or treat multiple common and serious diseases is a tantalizing prospect, observed Dr. Visvanathan, professor of epidemiology and oncology at Johns Hopkins University, Baltimore.

bjancin@frontlinemedcom.com

SAN DIEGO – Endometrial cancer patients who regularly took low-dose aspirin experienced markedly better 5-year disease-free and overall survival compared to nonusers in an observational study, Dr. Koji Matsuo reported at the annual meeting of the Society of Gynecologic Oncology.

This apparent survival-prolonging effect of aspirin was greatest in women who were obese, less than 60 years old, had type 1 endometrial cancer, and/or received postoperative whole pelvic radiotherapy. In fact, the benefits achieved statistical significance only in patients who fit into one or more of these subgroups, added Dr. Matsuo of the University of Southern California, Los Angeles.

Bruce Jancin/Frontline Medical News

He presented a multicenter retrospective study of 1,687 patients with surgically staged endometrial cancer, 158 of whom were regular users of low-dose aspirin for various reasons, mainly cardioprotection.

The 5-year disease-free survival rates in aspirin users and nonusers were 90.6% and 80.9%, respectively. The 5-year overall survival rates were 96.4%, compared with 87.3%. Aspirin users had a higher cardiovascular risk profile. Their mean BMI was 36.7 kg/m², versus 29.6 kg/m² for nonusers. Moreover, aspirin users were also significantly more likely to have hypertension, diabetes, and hypercholesterolemia, and to be taking medications to manage those conditions.

In a multivariate analysis controlled for age, ethnicity, obesity, medications, tumor grade, stage, and histology, as well as the use of postoperative radiation therapy or chemotherapy, the adjusted 5-year risk of disease progression was 54% lower among aspirin users than in nonusers. The risk of all-cause mortality was reduced by 77%, according to Dr. Matsuo.

Aspirin’s mechanism of anti-oncogenic benefit in the setting of endometrial cancer is believed to involve its ability to inhibit COX-2, thereby curbing the chronic inflammation that figures prominently in the disease. Dr. Matsuo called attention to a recent retrospective cohort study by investigators at Montefiore Medical Center in New York. In that study, concomitant use of aspirin and a statin by endometrial cancer patients was associated with a robust 75% reduction in the risk of cancer-specific mortality, compared with women on neither (Obstet Gynecol. 2015 Jul;126[1]:144-50).

Bruce Jancin/Frontline Medical News

On the separate issue of whether aspirin is also useful for prevention of endometrial cancer, Dr. Matsuo noted that a recent Danish meta-analysis demonstrated a significantly reduced risk of developing the malignancy in regular users of aspirin, particularly if obese. The relative risk reduction in obese aspirin users, compared with nonusers, amounted to 44% in case-control studies and 20% in cohort studies (Gynecol Oncol. 2016 Feb;140[2]:352-8).

Discussant Dr. Kala Visvanathan commented that while the usual caveats about nonrandomized studies such as Dr. Matsuo’s apply – they must be considered hypothesis-generating rather than definitive because of the possibility of unrecognized confounders – repurposing an old drug such as aspirin as a treatment for cancer has enormous appeal.

The safety profiles and drug interactions of older medications such as aspirin, statins, and metformin are well established. And the ability to use an inexpensive older drug to simultaneously prevent or treat multiple common and serious diseases is a tantalizing prospect, observed Dr. Visvanathan, professor of epidemiology and oncology at Johns Hopkins University, Baltimore.

bjancin@frontlinemedcom.com

SAN DIEGO – The presence of lymphovascular space invasion in the setting of early-stage endometrial cancer is a more potent independent predictor of associated pelvic lymph node metastases than previously recognized, Dr. Soledad Jorge reported at the annual meeting of the Society of Gynecologic Oncology.

Indeed, she found in her large, population-based study that lymphovascular space invasion (LVSI) was the strongest predictor of nodal disease, even more robust than tumor grade. LVSI also was associated with a 1.92-fold increased risk of mortality at 45 months’ follow-up after adjustment for the presence of lymph node metastases.

Bruce Jancin/Frontline Medical News

This was a study of 25,907 women with surgically staged endometrioid adenocarcinoma of the endometrium who underwent hysterectomy and lymphadenectomy during 2010-2012 and were registered in the National Cancer Data Base. Seventy-two percent of them had T1A disease, defined by less than 50% myometrial invasion, while the remaining 28% had T1B disease with greater than 50% myoinvasion, according to Dr. Jorge of Columbia University in New York.

LVSI was present in 15.2% of the women. Lymph node metastases were detected in 5% of the overall study population. Twenty-one percent of women with LVSI had positive pelvic lymph nodes, compared with just 2.1% of patients without LVSI, she said.

When patients were stratified by tumor depth and invasion, LVSI was independently associated with a 3- to 16-fold increased risk of nodal metastases. In a more comprehensive multivariate regression analysis adjusted for age, tumor stage and grade, and other demographic and clinical factors, the relative risk of lymph node metastases in patients with T1A disease and LVSI was increased 9.2-fold, compared with that of patients with no LVSI. Patients with T1B disease and LVSI were at 4.6-fold greater risk for lymph node metastases than were T1B patients without LVSI, Dr. Jorge said.

LVSI was associated with significantly reduced survival out to 45 months in all patient subgroups except those having Stage IA, grade 1 tumors.

Dr. Jorge reported having no financial conflicts regarding this study, which was conducted free of commercial support.

bjancin@frontlinemedcom.com

SAN DIEGO – The presence of lymphovascular space invasion in the setting of early-stage endometrial cancer is a more potent independent predictor of associated pelvic lymph node metastases than previously recognized, Dr. Soledad Jorge reported at the annual meeting of the Society of Gynecologic Oncology.

Indeed, she found in her large, population-based study that lymphovascular space invasion (LVSI) was the strongest predictor of nodal disease, even more robust than tumor grade. LVSI also was associated with a 1.92-fold increased risk of mortality at 45 months’ follow-up after adjustment for the presence of lymph node metastases.

Bruce Jancin/Frontline Medical News

This was a study of 25,907 women with surgically staged endometrioid adenocarcinoma of the endometrium who underwent hysterectomy and lymphadenectomy during 2010-2012 and were registered in the National Cancer Data Base. Seventy-two percent of them had T1A disease, defined by less than 50% myometrial invasion, while the remaining 28% had T1B disease with greater than 50% myoinvasion, according to Dr. Jorge of Columbia University in New York.

LVSI was present in 15.2% of the women. Lymph node metastases were detected in 5% of the overall study population. Twenty-one percent of women with LVSI had positive pelvic lymph nodes, compared with just 2.1% of patients without LVSI, she said.

When patients were stratified by tumor depth and invasion, LVSI was independently associated with a 3- to 16-fold increased risk of nodal metastases. In a more comprehensive multivariate regression analysis adjusted for age, tumor stage and grade, and other demographic and clinical factors, the relative risk of lymph node metastases in patients with T1A disease and LVSI was increased 9.2-fold, compared with that of patients with no LVSI. Patients with T1B disease and LVSI were at 4.6-fold greater risk for lymph node metastases than were T1B patients without LVSI, Dr. Jorge said.

LVSI was associated with significantly reduced survival out to 45 months in all patient subgroups except those having Stage IA, grade 1 tumors.

Dr. Jorge reported having no financial conflicts regarding this study, which was conducted free of commercial support.

bjancin@frontlinemedcom.com

SAN DIEGO – The presence of lymphovascular space invasion in the setting of early-stage endometrial cancer is a more potent independent predictor of associated pelvic lymph node metastases than previously recognized, Dr. Soledad Jorge reported at the annual meeting of the Society of Gynecologic Oncology.

Indeed, she found in her large, population-based study that lymphovascular space invasion (LVSI) was the strongest predictor of nodal disease, even more robust than tumor grade. LVSI also was associated with a 1.92-fold increased risk of mortality at 45 months’ follow-up after adjustment for the presence of lymph node metastases.

Bruce Jancin/Frontline Medical News

This was a study of 25,907 women with surgically staged endometrioid adenocarcinoma of the endometrium who underwent hysterectomy and lymphadenectomy during 2010-2012 and were registered in the National Cancer Data Base. Seventy-two percent of them had T1A disease, defined by less than 50% myometrial invasion, while the remaining 28% had T1B disease with greater than 50% myoinvasion, according to Dr. Jorge of Columbia University in New York.

LVSI was present in 15.2% of the women. Lymph node metastases were detected in 5% of the overall study population. Twenty-one percent of women with LVSI had positive pelvic lymph nodes, compared with just 2.1% of patients without LVSI, she said.

When patients were stratified by tumor depth and invasion, LVSI was independently associated with a 3- to 16-fold increased risk of nodal metastases. In a more comprehensive multivariate regression analysis adjusted for age, tumor stage and grade, and other demographic and clinical factors, the relative risk of lymph node metastases in patients with T1A disease and LVSI was increased 9.2-fold, compared with that of patients with no LVSI. Patients with T1B disease and LVSI were at 4.6-fold greater risk for lymph node metastases than were T1B patients without LVSI, Dr. Jorge said.

LVSI was associated with significantly reduced survival out to 45 months in all patient subgroups except those having Stage IA, grade 1 tumors.

Dr. Jorge reported having no financial conflicts regarding this study, which was conducted free of commercial support.

bjancin@frontlinemedcom.com

SAN DIEGO – Women with advanced ovarian cancer who possess a mutation in a homologous recombination DNA repair gene have impressively longer progression-free and overall survival in response to therapy than those who don’t, Dr. Barbara S. Norquist reported at the annual meeting of the Society of Gynecologic Oncology.

What’s more, these mutations are common in women with ovarian cancer. Of 1,195 patients with advanced ovarian cancer enrolled in the phase III Gynecology Oncology Group 218 trial, fully 25.7% – or 1 in 4 patients – had a mutation in BRCA1, BRCA2, or one of 14 other homologous recombination DNA repair genes included in the BROCA-HR gene panel test, according to Dr. Norquist, a gynecologic oncologist at the University of Washington, Seattle.

Defects in these genes were associated with improved survival in GOG 218. The most impressive gain in overall survival was seen in women with a BRCA2 mutation: their median overall survival was 33.1 months longer than in patients with no mutations.

In a multivariate analysis adjusted for treatment, stage, residual disease, and performance status, the likelihood of disease progression was reduced by 20% in patients with a BRCA1 mutation compared to women with no mutations, by 48% in patients with a BRCA2 mutation, and by 27% in those with non-BRCA HR mutations. The risk of death was reduced by 26% in patients with a BRCA1 mutation, by 64% in those with a BRCA2 mutation, and by 33% in those with other HR mutations, according to Dr. Norquist.

Mutation status proved unrelated to patient age, histologic tumor type, or family history. That’s a key finding, she stressed. The clinical implication is that all women with any type of ovarian cancer should undergo genetic testing for mutations in homologous recombination genes.

Forty-eight percent of women in the homologous recombination (HR) gene mutation-positive cohort had a damaging mutation in BRCA1, 25% in BRCA2, and 27% in one of the 14 other HR genes included in the BROCA-HR gene test panel. The BROCA-HR gene test panel was developed by University of Washington physicians and is commercially available through the university’s department of laboratory medicine. Dr. Norquist noted, however, that these 16 genes are included in most gene panel tests.

Testing only for BRCA1/2 mutations, while less expensive than testing for the full set of 16 HR genes, would have missed 27% of patients who had one of the other mutations linked to improved prognosis, she observed.

The GOG 218 study was a randomized, placebo-controlled trial designed to evaluate the impact of adding extended bevacizumab to first-line chemotherapy for advanced ovarian cancer. The main finding was that bevacizumab modestly improved progression-free survival by about 3 months (N Engl J Med. 2011 Dec 29;365(26):2473-83). Dr. Norquist’s secondary analysis of the GOG 218 dataset looked at whether HR mutation status could be used to identify a patient subset who would get a more robust benefit from bevacizumab; it did not.

“How I would interpret this clinically is that if a clinician feels their patient is a candidate for bevacizumab, we don’t have sufficient evidence at this time that mutation status should impact that decision,” she said.

Dr. Norquist was honored with the Society of Gynecologic Oncology annual President’s Award, bestowed for the study presented at the meeting which is judged to have the biggest direct effect on the care of women with gynecologic cancer.

Discussant Dr. Kristin Zorn was strongly supportive of the award going to Dr. Norquist.

“I think what this amounts to is a change in the standard of care for ovarian cancer. If you care for ovarian cancer patients, it’s imperative to have adequate training to provide genetic counseling and testing, or to know how to refer to appropriate genetic professionals in your practice setting,” according to Dr. Zorn of the University of Arkansas for Medical Sciences in Little Rock.

She endorsed Dr. Norquist’s call for genetic screening for HR deficiency in all patients with ovarian, fallopian tube, or primary peritoneal cancer regardless of tumor histology, family history of cancer, or ethnicity. Dr. Zorn noted that stance has been an underappreciated element in National Comprehensive Cancer Network guidelines since 2011.

“That knowledge of HR mutation status has such an impact for that patient and her family,” Dr. Zorn stressed.

Based upon other evidence, she added, it’s quite possible that the true proportion of ovarian cancer patients with HR deficiency could be as high as 50%, rather than the 26% figure Dr. Norquist reported in her GOG 218 analysis. That’s because for many participants in GOG 218, DNA was available from either germline or somatic samples, but not both.

The new understanding of the importance of HR deficiency has important implications for the design of clinical trials. At present many trials of potential new treatments for ovarian cancer restrict enrollment to patients with high-grade serous disease. It’s now clear that such restrictions exclude many patients who could benefit from drugs with activity in the setting of HR deficiency, Dr. Zorn said.

Homologous recombination deficiency increases tumor sensitivity to a variety of medications, including platinum, pegylated liposomal doxorubicin, antiangiogenic agents, and PARP inhibitors, she added.

The 16 HR genes Dr. Norquist scrutinized in GOG 218 are BRCA1/2, BRIP1, PALB2, RAD51C, RAD51D, ATM, ATR, NBN, SLX4, BARD1, BLM, CHEK2, RBBP8, MRE11A, and XRCC2. These genes lie along what has come to be called the Fanconi Anemia/BRCA homologous recombination pathway.

bjancin@frontlinemedcom.com

SAN DIEGO – Women with advanced ovarian cancer who possess a mutation in a homologous recombination DNA repair gene have impressively longer progression-free and overall survival in response to therapy than those who don’t, Dr. Barbara S. Norquist reported at the annual meeting of the Society of Gynecologic Oncology.

What’s more, these mutations are common in women with ovarian cancer. Of 1,195 patients with advanced ovarian cancer enrolled in the phase III Gynecology Oncology Group 218 trial, fully 25.7% – or 1 in 4 patients – had a mutation in BRCA1, BRCA2, or one of 14 other homologous recombination DNA repair genes included in the BROCA-HR gene panel test, according to Dr. Norquist, a gynecologic oncologist at the University of Washington, Seattle.

Defects in these genes were associated with improved survival in GOG 218. The most impressive gain in overall survival was seen in women with a BRCA2 mutation: their median overall survival was 33.1 months longer than in patients with no mutations.

In a multivariate analysis adjusted for treatment, stage, residual disease, and performance status, the likelihood of disease progression was reduced by 20% in patients with a BRCA1 mutation compared to women with no mutations, by 48% in patients with a BRCA2 mutation, and by 27% in those with non-BRCA HR mutations. The risk of death was reduced by 26% in patients with a BRCA1 mutation, by 64% in those with a BRCA2 mutation, and by 33% in those with other HR mutations, according to Dr. Norquist.

Mutation status proved unrelated to patient age, histologic tumor type, or family history. That’s a key finding, she stressed. The clinical implication is that all women with any type of ovarian cancer should undergo genetic testing for mutations in homologous recombination genes.

Forty-eight percent of women in the homologous recombination (HR) gene mutation-positive cohort had a damaging mutation in BRCA1, 25% in BRCA2, and 27% in one of the 14 other HR genes included in the BROCA-HR gene test panel. The BROCA-HR gene test panel was developed by University of Washington physicians and is commercially available through the university’s department of laboratory medicine. Dr. Norquist noted, however, that these 16 genes are included in most gene panel tests.

Testing only for BRCA1/2 mutations, while less expensive than testing for the full set of 16 HR genes, would have missed 27% of patients who had one of the other mutations linked to improved prognosis, she observed.

The GOG 218 study was a randomized, placebo-controlled trial designed to evaluate the impact of adding extended bevacizumab to first-line chemotherapy for advanced ovarian cancer. The main finding was that bevacizumab modestly improved progression-free survival by about 3 months (N Engl J Med. 2011 Dec 29;365(26):2473-83). Dr. Norquist’s secondary analysis of the GOG 218 dataset looked at whether HR mutation status could be used to identify a patient subset who would get a more robust benefit from bevacizumab; it did not.

“How I would interpret this clinically is that if a clinician feels their patient is a candidate for bevacizumab, we don’t have sufficient evidence at this time that mutation status should impact that decision,” she said.

Dr. Norquist was honored with the Society of Gynecologic Oncology annual President’s Award, bestowed for the study presented at the meeting which is judged to have the biggest direct effect on the care of women with gynecologic cancer.

Discussant Dr. Kristin Zorn was strongly supportive of the award going to Dr. Norquist.

“I think what this amounts to is a change in the standard of care for ovarian cancer. If you care for ovarian cancer patients, it’s imperative to have adequate training to provide genetic counseling and testing, or to know how to refer to appropriate genetic professionals in your practice setting,” according to Dr. Zorn of the University of Arkansas for Medical Sciences in Little Rock.

She endorsed Dr. Norquist’s call for genetic screening for HR deficiency in all patients with ovarian, fallopian tube, or primary peritoneal cancer regardless of tumor histology, family history of cancer, or ethnicity. Dr. Zorn noted that stance has been an underappreciated element in National Comprehensive Cancer Network guidelines since 2011.

“That knowledge of HR mutation status has such an impact for that patient and her family,” Dr. Zorn stressed.

Based upon other evidence, she added, it’s quite possible that the true proportion of ovarian cancer patients with HR deficiency could be as high as 50%, rather than the 26% figure Dr. Norquist reported in her GOG 218 analysis. That’s because for many participants in GOG 218, DNA was available from either germline or somatic samples, but not both.

The new understanding of the importance of HR deficiency has important implications for the design of clinical trials. At present many trials of potential new treatments for ovarian cancer restrict enrollment to patients with high-grade serous disease. It’s now clear that such restrictions exclude many patients who could benefit from drugs with activity in the setting of HR deficiency, Dr. Zorn said.

Homologous recombination deficiency increases tumor sensitivity to a variety of medications, including platinum, pegylated liposomal doxorubicin, antiangiogenic agents, and PARP inhibitors, she added.

The 16 HR genes Dr. Norquist scrutinized in GOG 218 are BRCA1/2, BRIP1, PALB2, RAD51C, RAD51D, ATM, ATR, NBN, SLX4, BARD1, BLM, CHEK2, RBBP8, MRE11A, and XRCC2. These genes lie along what has come to be called the Fanconi Anemia/BRCA homologous recombination pathway.

bjancin@frontlinemedcom.com

SAN DIEGO – Women with advanced ovarian cancer who possess a mutation in a homologous recombination DNA repair gene have impressively longer progression-free and overall survival in response to therapy than those who don’t, Dr. Barbara S. Norquist reported at the annual meeting of the Society of Gynecologic Oncology.

What’s more, these mutations are common in women with ovarian cancer. Of 1,195 patients with advanced ovarian cancer enrolled in the phase III Gynecology Oncology Group 218 trial, fully 25.7% – or 1 in 4 patients – had a mutation in BRCA1, BRCA2, or one of 14 other homologous recombination DNA repair genes included in the BROCA-HR gene panel test, according to Dr. Norquist, a gynecologic oncologist at the University of Washington, Seattle.

Defects in these genes were associated with improved survival in GOG 218. The most impressive gain in overall survival was seen in women with a BRCA2 mutation: their median overall survival was 33.1 months longer than in patients with no mutations.

In a multivariate analysis adjusted for treatment, stage, residual disease, and performance status, the likelihood of disease progression was reduced by 20% in patients with a BRCA1 mutation compared to women with no mutations, by 48% in patients with a BRCA2 mutation, and by 27% in those with non-BRCA HR mutations. The risk of death was reduced by 26% in patients with a BRCA1 mutation, by 64% in those with a BRCA2 mutation, and by 33% in those with other HR mutations, according to Dr. Norquist.

Mutation status proved unrelated to patient age, histologic tumor type, or family history. That’s a key finding, she stressed. The clinical implication is that all women with any type of ovarian cancer should undergo genetic testing for mutations in homologous recombination genes.

Forty-eight percent of women in the homologous recombination (HR) gene mutation-positive cohort had a damaging mutation in BRCA1, 25% in BRCA2, and 27% in one of the 14 other HR genes included in the BROCA-HR gene test panel. The BROCA-HR gene test panel was developed by University of Washington physicians and is commercially available through the university’s department of laboratory medicine. Dr. Norquist noted, however, that these 16 genes are included in most gene panel tests.

Testing only for BRCA1/2 mutations, while less expensive than testing for the full set of 16 HR genes, would have missed 27% of patients who had one of the other mutations linked to improved prognosis, she observed.

The GOG 218 study was a randomized, placebo-controlled trial designed to evaluate the impact of adding extended bevacizumab to first-line chemotherapy for advanced ovarian cancer. The main finding was that bevacizumab modestly improved progression-free survival by about 3 months (N Engl J Med. 2011 Dec 29;365(26):2473-83). Dr. Norquist’s secondary analysis of the GOG 218 dataset looked at whether HR mutation status could be used to identify a patient subset who would get a more robust benefit from bevacizumab; it did not.

“How I would interpret this clinically is that if a clinician feels their patient is a candidate for bevacizumab, we don’t have sufficient evidence at this time that mutation status should impact that decision,” she said.

Dr. Norquist was honored with the Society of Gynecologic Oncology annual President’s Award, bestowed for the study presented at the meeting which is judged to have the biggest direct effect on the care of women with gynecologic cancer.

Discussant Dr. Kristin Zorn was strongly supportive of the award going to Dr. Norquist.

“I think what this amounts to is a change in the standard of care for ovarian cancer. If you care for ovarian cancer patients, it’s imperative to have adequate training to provide genetic counseling and testing, or to know how to refer to appropriate genetic professionals in your practice setting,” according to Dr. Zorn of the University of Arkansas for Medical Sciences in Little Rock.

She endorsed Dr. Norquist’s call for genetic screening for HR deficiency in all patients with ovarian, fallopian tube, or primary peritoneal cancer regardless of tumor histology, family history of cancer, or ethnicity. Dr. Zorn noted that stance has been an underappreciated element in National Comprehensive Cancer Network guidelines since 2011.

“That knowledge of HR mutation status has such an impact for that patient and her family,” Dr. Zorn stressed.

Based upon other evidence, she added, it’s quite possible that the true proportion of ovarian cancer patients with HR deficiency could be as high as 50%, rather than the 26% figure Dr. Norquist reported in her GOG 218 analysis. That’s because for many participants in GOG 218, DNA was available from either germline or somatic samples, but not both.

The new understanding of the importance of HR deficiency has important implications for the design of clinical trials. At present many trials of potential new treatments for ovarian cancer restrict enrollment to patients with high-grade serous disease. It’s now clear that such restrictions exclude many patients who could benefit from drugs with activity in the setting of HR deficiency, Dr. Zorn said.

Homologous recombination deficiency increases tumor sensitivity to a variety of medications, including platinum, pegylated liposomal doxorubicin, antiangiogenic agents, and PARP inhibitors, she added.

The 16 HR genes Dr. Norquist scrutinized in GOG 218 are BRCA1/2, BRIP1, PALB2, RAD51C, RAD51D, ATM, ATR, NBN, SLX4, BARD1, BLM, CHEK2, RBBP8, MRE11A, and XRCC2. These genes lie along what has come to be called the Fanconi Anemia/BRCA homologous recombination pathway.

bjancin@frontlinemedcom.com

MAUI, HAWAII – Oral mongersen shows promise of being an ideal treatment for inflammatory bowel disease (IBD) if the promising phase II results are confirmed in phase III clinical trials, Dr. Uma Mahadevan, AGAF, said at the 2016 Rheumatology Winter Clinical Symposium.*

This perfect drug for IBD would be something that’s effective, safe, and well tolerated; orally administered; shows long-term efficacy; and can be dosed as needed. Preliminary indications are that mongersen may check off those boxes, according to Dr. Mahadevan, professor of medicine and joint medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.

An Italian double-blind, placebo-controlled, phase II study of mongersen in Crohn’s disease generated enormous attention among IBD patients and gastroenterologists, with reported day 15 clinical remission rates of 55% and 65% at 40 and 160 mg/day, respectively (N Engl J Med. 2015 Mar 19;372:1104-13).

“We haven’t seen numbers like that in a Crohn’s trial since the very first Remicade [infliximab] trial. So there’s a lot of excitement about it. The study mechanics are a little suspect, but if the data in the current phase III trials are half as good, mongersen may be what we’re looking for,” Dr. Mahadevan said.

Mongersen is an oligonucleotide that inhibits ileal and colonic SMAD7, a protein that prevents transforming growth factor beta₁–mediated suppression of inflammatory genes.

Why was a gastroenterologist providing an IBD update at a rheumatology conference? Dr. Mahadevan was invited in order to provide the conference’s annual “Outside the Box” feature, in which a nonrheumatologist expert shares the latest thinking about a disease relevant to rheumatology.

IBD fills the bill for several reasons. For one, many of the extraintestinal manifestations of IBD overlap with rheumatologic conditions. These include uveitis, arthritis, and arthralgias; osteopenia and osteoporosis; psoriasiform skin lesions; and thromboembolism. It’s not unusual for these extraintestinal manifestations to bring a patient to a nongastroenterologist before the diagnosis of IBD has been made.

Also, gastroenterologists and rheumatologists use a lot of the same drugs.

“The only drug gastroenterologists use for IBD that didn’t come from rheumatology first is vedolizumab [Entyvio],” she observed.

Ustekinumab (Stelara), which Dr. Mahadevan and other IBD experts have been using off-label for refractory Crohn’s disease with what she termed “very good” results, is expected to receive an Food and Drug Administration indication for Crohn’s disease by year’s end on the strength of impressive phase III data reported last fall.

“When approved, ustekinumab should be a first-line therapy, parallel to the TNF [tumor necrosis factor] inhibitors,” she predicted.

Another reason it’s worthwhile for rheumatologists to be up to date on IBD is that in many parts of the country, some gastroenterologists in community practice are uncomfortable using TNF inhibitors, which are now standard therapy for IBD. They may refer those patients to their local rheumatologist. But be advised: the dosing is very different from in rheumatology.

“For example, you start adalimumab [Humira] at 40 mg every other week for rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, but we [gastroenterologists] do a loading dose of four 40-mg injections on day 1, then 80 mg 2 weeks later, and then maintenance dosing at 40 mg every 2 weeks. Sometimes in our patient population you’re not going to get a response unless you use a high dose like that,” the gastroenterologist explained.

The incidence of IBD is climbing. It was estimated at 5-7 cases per 100,000 population in the late 1990s, but it’s now believed to be 7-12 per 100,000. The peak age of onset is still in 15- to 30-year-olds, but now physicians are seeing a strong second peak later in life, among individuals in their 60s and 70s. And while Caucasians and Ashkenazi Jews have traditionally been thought of as the groups at increased risk for IBD, treatment centers are now springing up in India, China, and other countries where IBD was formerly thought to be less common.

“What is happening? Is it that because of better medical care we’re now picking up more cases outside of North America and Europe? Or is it a change in the environment – the microbiome, the Westernized diet, pollution? We really don’t know. But this is where a lot of study is going,” according to Dr. Mahadevan.

Something nongastroenterologists need to know about the clinical care of IBD patients is that even though TNF inhibitors are now considered standard therapy for patients with more severe disease and these biologic agents are routinely used in IBD centers of excellence, their penetration into community practice has been slow. Although high-dose anti-TNF therapy is supposed to be employed in ulcerative colitis patients who are refractory to corticosteroid induction therapy or who are steroid dependent, it’s fairly common in some parts of the country for a patient to undergo colectomy without ever having received an anti-TNF biologic.

“If you’re in a surgery-dominated area, the surgeons were very influenced by a Cleveland Clinic paper that said patients who received infliximab had more complications after surgery. There were a lot of caveats to that paper, but colorectal surgeons don’t want you to use a TNF inhibitor if they feel the patient is going to surgery,” she said.

In addition to mongersen, other novel agents targeting new pathways in IBD include the oral Janus-associated kinase inhibitor tofacitinib (Xeljanz), under study for both ulcerative colitis and Crohn’s disease; ozanimod, an oral sphingosine 1–phosphate 1 and 5 receptor modulator in clinical trials for ulcerative colitis; and the humanized monoclonal antibody etrolizumab, a selective anti-integrin agent.

Dr. Mahadevan reported serving as a consultant to and/or research grant recipient from more than half a dozen pharmaceutical companies.

*Changes were made to this story on March 24, 2016.

bjancin@frontlinemedcom.com

MAUI, HAWAII – Oral mongersen shows promise of being an ideal treatment for inflammatory bowel disease (IBD) if the promising phase II results are confirmed in phase III clinical trials, Dr. Uma Mahadevan, AGAF, said at the 2016 Rheumatology Winter Clinical Symposium.*

This perfect drug for IBD would be something that’s effective, safe, and well tolerated; orally administered; shows long-term efficacy; and can be dosed as needed. Preliminary indications are that mongersen may check off those boxes, according to Dr. Mahadevan, professor of medicine and joint medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.

An Italian double-blind, placebo-controlled, phase II study of mongersen in Crohn’s disease generated enormous attention among IBD patients and gastroenterologists, with reported day 15 clinical remission rates of 55% and 65% at 40 and 160 mg/day, respectively (N Engl J Med. 2015 Mar 19;372:1104-13).

“We haven’t seen numbers like that in a Crohn’s trial since the very first Remicade [infliximab] trial. So there’s a lot of excitement about it. The study mechanics are a little suspect, but if the data in the current phase III trials are half as good, mongersen may be what we’re looking for,” Dr. Mahadevan said.

Mongersen is an oligonucleotide that inhibits ileal and colonic SMAD7, a protein that prevents transforming growth factor beta₁–mediated suppression of inflammatory genes.

Why was a gastroenterologist providing an IBD update at a rheumatology conference? Dr. Mahadevan was invited in order to provide the conference’s annual “Outside the Box” feature, in which a nonrheumatologist expert shares the latest thinking about a disease relevant to rheumatology.

IBD fills the bill for several reasons. For one, many of the extraintestinal manifestations of IBD overlap with rheumatologic conditions. These include uveitis, arthritis, and arthralgias; osteopenia and osteoporosis; psoriasiform skin lesions; and thromboembolism. It’s not unusual for these extraintestinal manifestations to bring a patient to a nongastroenterologist before the diagnosis of IBD has been made.

Also, gastroenterologists and rheumatologists use a lot of the same drugs.

“The only drug gastroenterologists use for IBD that didn’t come from rheumatology first is vedolizumab [Entyvio],” she observed.

Ustekinumab (Stelara), which Dr. Mahadevan and other IBD experts have been using off-label for refractory Crohn’s disease with what she termed “very good” results, is expected to receive an Food and Drug Administration indication for Crohn’s disease by year’s end on the strength of impressive phase III data reported last fall.

“When approved, ustekinumab should be a first-line therapy, parallel to the TNF [tumor necrosis factor] inhibitors,” she predicted.

Another reason it’s worthwhile for rheumatologists to be up to date on IBD is that in many parts of the country, some gastroenterologists in community practice are uncomfortable using TNF inhibitors, which are now standard therapy for IBD. They may refer those patients to their local rheumatologist. But be advised: the dosing is very different from in rheumatology.

“For example, you start adalimumab [Humira] at 40 mg every other week for rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, but we [gastroenterologists] do a loading dose of four 40-mg injections on day 1, then 80 mg 2 weeks later, and then maintenance dosing at 40 mg every 2 weeks. Sometimes in our patient population you’re not going to get a response unless you use a high dose like that,” the gastroenterologist explained.

The incidence of IBD is climbing. It was estimated at 5-7 cases per 100,000 population in the late 1990s, but it’s now believed to be 7-12 per 100,000. The peak age of onset is still in 15- to 30-year-olds, but now physicians are seeing a strong second peak later in life, among individuals in their 60s and 70s. And while Caucasians and Ashkenazi Jews have traditionally been thought of as the groups at increased risk for IBD, treatment centers are now springing up in India, China, and other countries where IBD was formerly thought to be less common.

“What is happening? Is it that because of better medical care we’re now picking up more cases outside of North America and Europe? Or is it a change in the environment – the microbiome, the Westernized diet, pollution? We really don’t know. But this is where a lot of study is going,” according to Dr. Mahadevan.

Something nongastroenterologists need to know about the clinical care of IBD patients is that even though TNF inhibitors are now considered standard therapy for patients with more severe disease and these biologic agents are routinely used in IBD centers of excellence, their penetration into community practice has been slow. Although high-dose anti-TNF therapy is supposed to be employed in ulcerative colitis patients who are refractory to corticosteroid induction therapy or who are steroid dependent, it’s fairly common in some parts of the country for a patient to undergo colectomy without ever having received an anti-TNF biologic.

“If you’re in a surgery-dominated area, the surgeons were very influenced by a Cleveland Clinic paper that said patients who received infliximab had more complications after surgery. There were a lot of caveats to that paper, but colorectal surgeons don’t want you to use a TNF inhibitor if they feel the patient is going to surgery,” she said.

In addition to mongersen, other novel agents targeting new pathways in IBD include the oral Janus-associated kinase inhibitor tofacitinib (Xeljanz), under study for both ulcerative colitis and Crohn’s disease; ozanimod, an oral sphingosine 1–phosphate 1 and 5 receptor modulator in clinical trials for ulcerative colitis; and the humanized monoclonal antibody etrolizumab, a selective anti-integrin agent.

Dr. Mahadevan reported serving as a consultant to and/or research grant recipient from more than half a dozen pharmaceutical companies.

*Changes were made to this story on March 24, 2016.

bjancin@frontlinemedcom.com

MAUI, HAWAII – Oral mongersen shows promise of being an ideal treatment for inflammatory bowel disease (IBD) if the promising phase II results are confirmed in phase III clinical trials, Dr. Uma Mahadevan, AGAF, said at the 2016 Rheumatology Winter Clinical Symposium.*

This perfect drug for IBD would be something that’s effective, safe, and well tolerated; orally administered; shows long-term efficacy; and can be dosed as needed. Preliminary indications are that mongersen may check off those boxes, according to Dr. Mahadevan, professor of medicine and joint medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.

An Italian double-blind, placebo-controlled, phase II study of mongersen in Crohn’s disease generated enormous attention among IBD patients and gastroenterologists, with reported day 15 clinical remission rates of 55% and 65% at 40 and 160 mg/day, respectively (N Engl J Med. 2015 Mar 19;372:1104-13).

“We haven’t seen numbers like that in a Crohn’s trial since the very first Remicade [infliximab] trial. So there’s a lot of excitement about it. The study mechanics are a little suspect, but if the data in the current phase III trials are half as good, mongersen may be what we’re looking for,” Dr. Mahadevan said.

Mongersen is an oligonucleotide that inhibits ileal and colonic SMAD7, a protein that prevents transforming growth factor beta₁–mediated suppression of inflammatory genes.

Why was a gastroenterologist providing an IBD update at a rheumatology conference? Dr. Mahadevan was invited in order to provide the conference’s annual “Outside the Box” feature, in which a nonrheumatologist expert shares the latest thinking about a disease relevant to rheumatology.

IBD fills the bill for several reasons. For one, many of the extraintestinal manifestations of IBD overlap with rheumatologic conditions. These include uveitis, arthritis, and arthralgias; osteopenia and osteoporosis; psoriasiform skin lesions; and thromboembolism. It’s not unusual for these extraintestinal manifestations to bring a patient to a nongastroenterologist before the diagnosis of IBD has been made.

Also, gastroenterologists and rheumatologists use a lot of the same drugs.

“The only drug gastroenterologists use for IBD that didn’t come from rheumatology first is vedolizumab [Entyvio],” she observed.

Ustekinumab (Stelara), which Dr. Mahadevan and other IBD experts have been using off-label for refractory Crohn’s disease with what she termed “very good” results, is expected to receive an Food and Drug Administration indication for Crohn’s disease by year’s end on the strength of impressive phase III data reported last fall.

“When approved, ustekinumab should be a first-line therapy, parallel to the TNF [tumor necrosis factor] inhibitors,” she predicted.

Another reason it’s worthwhile for rheumatologists to be up to date on IBD is that in many parts of the country, some gastroenterologists in community practice are uncomfortable using TNF inhibitors, which are now standard therapy for IBD. They may refer those patients to their local rheumatologist. But be advised: the dosing is very different from in rheumatology.

“For example, you start adalimumab [Humira] at 40 mg every other week for rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, but we [gastroenterologists] do a loading dose of four 40-mg injections on day 1, then 80 mg 2 weeks later, and then maintenance dosing at 40 mg every 2 weeks. Sometimes in our patient population you’re not going to get a response unless you use a high dose like that,” the gastroenterologist explained.

The incidence of IBD is climbing. It was estimated at 5-7 cases per 100,000 population in the late 1990s, but it’s now believed to be 7-12 per 100,000. The peak age of onset is still in 15- to 30-year-olds, but now physicians are seeing a strong second peak later in life, among individuals in their 60s and 70s. And while Caucasians and Ashkenazi Jews have traditionally been thought of as the groups at increased risk for IBD, treatment centers are now springing up in India, China, and other countries where IBD was formerly thought to be less common.

“What is happening? Is it that because of better medical care we’re now picking up more cases outside of North America and Europe? Or is it a change in the environment – the microbiome, the Westernized diet, pollution? We really don’t know. But this is where a lot of study is going,” according to Dr. Mahadevan.

Something nongastroenterologists need to know about the clinical care of IBD patients is that even though TNF inhibitors are now considered standard therapy for patients with more severe disease and these biologic agents are routinely used in IBD centers of excellence, their penetration into community practice has been slow. Although high-dose anti-TNF therapy is supposed to be employed in ulcerative colitis patients who are refractory to corticosteroid induction therapy or who are steroid dependent, it’s fairly common in some parts of the country for a patient to undergo colectomy without ever having received an anti-TNF biologic.

“If you’re in a surgery-dominated area, the surgeons were very influenced by a Cleveland Clinic paper that said patients who received infliximab had more complications after surgery. There were a lot of caveats to that paper, but colorectal surgeons don’t want you to use a TNF inhibitor if they feel the patient is going to surgery,” she said.

In addition to mongersen, other novel agents targeting new pathways in IBD include the oral Janus-associated kinase inhibitor tofacitinib (Xeljanz), under study for both ulcerative colitis and Crohn’s disease; ozanimod, an oral sphingosine 1–phosphate 1 and 5 receptor modulator in clinical trials for ulcerative colitis; and the humanized monoclonal antibody etrolizumab, a selective anti-integrin agent.

Dr. Mahadevan reported serving as a consultant to and/or research grant recipient from more than half a dozen pharmaceutical companies.

*Changes were made to this story on March 24, 2016.

bjancin@frontlinemedcom.com

MAUI, HAWAII – Now is a good time to assess the future of the Janus kinase inhibitor class of oral small-molecule medications for rheumatoid arthritis based on new evidence that addresses many of the key questions rheumatologists have about these agents, Dr. Roy Fleischmann said at the 2016 Rheumatology Winter Clinical Symposium.

Baricitinib is likely to win Food and Drug Administration approval within a year, and would join tofacitinib (Xeljanz) as the second Janus kinase (JAK) inhibitor. A once-daily formulation of tofacitinib also was recently approved. Additional investigational agents, filgotinib and ABT-494, are headed for phase III testing, noted Dr. Fleischmann of the University of Texas Southwestern Medical Center and co–medical director of the Metroplex Clinical Research Center, Dallas.

Bruce Jancin/Frontline Medical News

Here’s what rheumatologists want to know about the Janus associated kinase inhibitors, or Jakinibs:

Does Jakinib monotherapy look like a viable strategy?

Yes, according to Dr. Fleischmann, who pointed to the RA-BEGIN baricitinib trial and the DARWIN2 filgotinib trial, both presented at last fall’s American College of Rheumatology annual meeting in San Francisco.

Dr. Fleischmann presented the RA-BEGIN results at the American College of Rheumatology meeting. In this randomized trial conducted in methotrexate-naive rheumatoid arthritis patients, baricitinib 4 mg/day monotherapy outperformed methotrexate in terms of ACR response and demonstrated efficacy similar to baricitinib plus methotrexate, but with fewer side effects. Radiographic disease progression was significantly greater over 52 weeks with methotrexate than with baricitinib monotherapy, and significantly greater with baricitinib monotherapy than with combination therapy. However, baricitinib monotherapy was as effective as baricitinib in combination with methotrexate in slowing disease progression among patients who had elevated high-sensitivity C-reactive protein before treatment that normalized in response to therapy.

“So if baricitinib is approved and is available, I would use it as monotherapy initially and watch the C-reactive protein. If it drops to normal I’m fine, and if it doesn’t I’d add methotrexate for combination therapy,” according to the rheumatologist.

The randomized DARWIN2 trial included 283 methotrexate inadequate responders and showed that filgotinib is also effective as monotherapy.

“Tofacitinib, baricitinib, and filgotinib all work as monotherapy, and why shouldn’t they? There are no antibodies because these are small molecules,” Dr. Fleischmann commented.

A key safety finding in RA-BEAM, in his view, was that herpes zoster occurred in 1.4% of baricitinib-treated patients as well as in 1.2% of the adalimumab (Humira) arm.

“The message here, I think, is that we should be thinking about zoster in all patients with rheumatoid arthritis,” he said.

Is there a clinically meaningful efficacy difference between the Jakinibs?

Not so far, but as yet there have been no head-to-head trials.

How about in terms of safety?

“Safety may be the difference between these drugs. Efficacy doesn’t seem that different,” he said.

Based upon the clinical trials data to date, which involves hundreds of patients per Jakinib, it appears there is a hint of a difference, with less lymphopenia and anemia being seen with filgotinib, the most JAK 1–selective of the Jakinibs. Baricitinib is a JAK 1/2 inhibitor, tofacitinib a JAK 3/1/2 inhibitor, and ABT-494 is relatively JAK 1–selective. But definitive answers regarding comparative safety must await the creation of multi-thousand-patient postmarketing registries, in Dr. Fleischmann’s opinion.

Which is more effective: a Jakinib or a tumor necrosis factor inhibitor?

Only one clinical trial has addressed this question with sufficient power to yield a statistically significant answer. This was the RA-BEAM trial presented at the 2015 ACR meeting. RA-BEAM was a randomized head-to-head study of baricitinib plus methotrexate versus adalimumab plus methotrexate in 1,305 methotrexate inadequate responders. Baricitinib was the clear winner, with week 24 ACR 20 and ACR 50 responses of 70% and 45%, respectively, compared with 61% and 35% for adalimumab. Particularly impressive was baricitinib’s outperformance of adalimumab on the pain component of the ACR score.

“This is the first study to show a Jakinib plus methotrexate is actually superior to a TNF inhibitor plus methotrexate. And adalimumab is a really, really good drug. Is it a big difference? It’s not tremendous, but it’s a difference. Is it clinically significant? In that extra 9%-10% of patients, it obviously is; in most it’s probably not,” Dr. Fleischmann said.

Will an oral Jakinib be the first drug physicians prescribe in rheumatoid arthritis patients, or the last?

“The data so far shows that Jakinib monotherapy is very viable, as opposed to biologic monotherapy, which is viable but less so. RA-BEAM showed baricitinib was superior to a TNF inhibitor, and there are studies to suggest but don’t prove that tofacitinib is, too,” he said.

Dr. Fleischmann reported serving as a paid researcher for and/or consultant to numerous pharmaceutical companies, including most of those developing Jakinibs.

bjancin@frontlinemedcom.com

MAUI, HAWAII – Now is a good time to assess the future of the Janus kinase inhibitor class of oral small-molecule medications for rheumatoid arthritis based on new evidence that addresses many of the key questions rheumatologists have about these agents, Dr. Roy Fleischmann said at the 2016 Rheumatology Winter Clinical Symposium.

Baricitinib is likely to win Food and Drug Administration approval within a year, and would join tofacitinib (Xeljanz) as the second Janus kinase (JAK) inhibitor. A once-daily formulation of tofacitinib also was recently approved. Additional investigational agents, filgotinib and ABT-494, are headed for phase III testing, noted Dr. Fleischmann of the University of Texas Southwestern Medical Center and co–medical director of the Metroplex Clinical Research Center, Dallas.

Bruce Jancin/Frontline Medical News

Here’s what rheumatologists want to know about the Janus associated kinase inhibitors, or Jakinibs:

Does Jakinib monotherapy look like a viable strategy?

Yes, according to Dr. Fleischmann, who pointed to the RA-BEGIN baricitinib trial and the DARWIN2 filgotinib trial, both presented at last fall’s American College of Rheumatology annual meeting in San Francisco.

Dr. Fleischmann presented the RA-BEGIN results at the American College of Rheumatology meeting. In this randomized trial conducted in methotrexate-naive rheumatoid arthritis patients, baricitinib 4 mg/day monotherapy outperformed methotrexate in terms of ACR response and demonstrated efficacy similar to baricitinib plus methotrexate, but with fewer side effects. Radiographic disease progression was significantly greater over 52 weeks with methotrexate than with baricitinib monotherapy, and significantly greater with baricitinib monotherapy than with combination therapy. However, baricitinib monotherapy was as effective as baricitinib in combination with methotrexate in slowing disease progression among patients who had elevated high-sensitivity C-reactive protein before treatment that normalized in response to therapy.

“So if baricitinib is approved and is available, I would use it as monotherapy initially and watch the C-reactive protein. If it drops to normal I’m fine, and if it doesn’t I’d add methotrexate for combination therapy,” according to the rheumatologist.

The randomized DARWIN2 trial included 283 methotrexate inadequate responders and showed that filgotinib is also effective as monotherapy.

“Tofacitinib, baricitinib, and filgotinib all work as monotherapy, and why shouldn’t they? There are no antibodies because these are small molecules,” Dr. Fleischmann commented.

A key safety finding in RA-BEAM, in his view, was that herpes zoster occurred in 1.4% of baricitinib-treated patients as well as in 1.2% of the adalimumab (Humira) arm.

“The message here, I think, is that we should be thinking about zoster in all patients with rheumatoid arthritis,” he said.

Is there a clinically meaningful efficacy difference between the Jakinibs?

Not so far, but as yet there have been no head-to-head trials.

How about in terms of safety?

“Safety may be the difference between these drugs. Efficacy doesn’t seem that different,” he said.

Based upon the clinical trials data to date, which involves hundreds of patients per Jakinib, it appears there is a hint of a difference, with less lymphopenia and anemia being seen with filgotinib, the most JAK 1–selective of the Jakinibs. Baricitinib is a JAK 1/2 inhibitor, tofacitinib a JAK 3/1/2 inhibitor, and ABT-494 is relatively JAK 1–selective. But definitive answers regarding comparative safety must await the creation of multi-thousand-patient postmarketing registries, in Dr. Fleischmann’s opinion.

Which is more effective: a Jakinib or a tumor necrosis factor inhibitor?

Only one clinical trial has addressed this question with sufficient power to yield a statistically significant answer. This was the RA-BEAM trial presented at the 2015 ACR meeting. RA-BEAM was a randomized head-to-head study of baricitinib plus methotrexate versus adalimumab plus methotrexate in 1,305 methotrexate inadequate responders. Baricitinib was the clear winner, with week 24 ACR 20 and ACR 50 responses of 70% and 45%, respectively, compared with 61% and 35% for adalimumab. Particularly impressive was baricitinib’s outperformance of adalimumab on the pain component of the ACR score.

“This is the first study to show a Jakinib plus methotrexate is actually superior to a TNF inhibitor plus methotrexate. And adalimumab is a really, really good drug. Is it a big difference? It’s not tremendous, but it’s a difference. Is it clinically significant? In that extra 9%-10% of patients, it obviously is; in most it’s probably not,” Dr. Fleischmann said.

Will an oral Jakinib be the first drug physicians prescribe in rheumatoid arthritis patients, or the last?

“The data so far shows that Jakinib monotherapy is very viable, as opposed to biologic monotherapy, which is viable but less so. RA-BEAM showed baricitinib was superior to a TNF inhibitor, and there are studies to suggest but don’t prove that tofacitinib is, too,” he said.

Dr. Fleischmann reported serving as a paid researcher for and/or consultant to numerous pharmaceutical companies, including most of those developing Jakinibs.

bjancin@frontlinemedcom.com

MAUI, HAWAII – Now is a good time to assess the future of the Janus kinase inhibitor class of oral small-molecule medications for rheumatoid arthritis based on new evidence that addresses many of the key questions rheumatologists have about these agents, Dr. Roy Fleischmann said at the 2016 Rheumatology Winter Clinical Symposium.

Baricitinib is likely to win Food and Drug Administration approval within a year, and would join tofacitinib (Xeljanz) as the second Janus kinase (JAK) inhibitor. A once-daily formulation of tofacitinib also was recently approved. Additional investigational agents, filgotinib and ABT-494, are headed for phase III testing, noted Dr. Fleischmann of the University of Texas Southwestern Medical Center and co–medical director of the Metroplex Clinical Research Center, Dallas.

Bruce Jancin/Frontline Medical News

Here’s what rheumatologists want to know about the Janus associated kinase inhibitors, or Jakinibs:

Does Jakinib monotherapy look like a viable strategy?

Yes, according to Dr. Fleischmann, who pointed to the RA-BEGIN baricitinib trial and the DARWIN2 filgotinib trial, both presented at last fall’s American College of Rheumatology annual meeting in San Francisco.

Dr. Fleischmann presented the RA-BEGIN results at the American College of Rheumatology meeting. In this randomized trial conducted in methotrexate-naive rheumatoid arthritis patients, baricitinib 4 mg/day monotherapy outperformed methotrexate in terms of ACR response and demonstrated efficacy similar to baricitinib plus methotrexate, but with fewer side effects. Radiographic disease progression was significantly greater over 52 weeks with methotrexate than with baricitinib monotherapy, and significantly greater with baricitinib monotherapy than with combination therapy. However, baricitinib monotherapy was as effective as baricitinib in combination with methotrexate in slowing disease progression among patients who had elevated high-sensitivity C-reactive protein before treatment that normalized in response to therapy.

“So if baricitinib is approved and is available, I would use it as monotherapy initially and watch the C-reactive protein. If it drops to normal I’m fine, and if it doesn’t I’d add methotrexate for combination therapy,” according to the rheumatologist.

The randomized DARWIN2 trial included 283 methotrexate inadequate responders and showed that filgotinib is also effective as monotherapy.

“Tofacitinib, baricitinib, and filgotinib all work as monotherapy, and why shouldn’t they? There are no antibodies because these are small molecules,” Dr. Fleischmann commented.

A key safety finding in RA-BEAM, in his view, was that herpes zoster occurred in 1.4% of baricitinib-treated patients as well as in 1.2% of the adalimumab (Humira) arm.

“The message here, I think, is that we should be thinking about zoster in all patients with rheumatoid arthritis,” he said.

Is there a clinically meaningful efficacy difference between the Jakinibs?

Not so far, but as yet there have been no head-to-head trials.

How about in terms of safety?

“Safety may be the difference between these drugs. Efficacy doesn’t seem that different,” he said.

Based upon the clinical trials data to date, which involves hundreds of patients per Jakinib, it appears there is a hint of a difference, with less lymphopenia and anemia being seen with filgotinib, the most JAK 1–selective of the Jakinibs. Baricitinib is a JAK 1/2 inhibitor, tofacitinib a JAK 3/1/2 inhibitor, and ABT-494 is relatively JAK 1–selective. But definitive answers regarding comparative safety must await the creation of multi-thousand-patient postmarketing registries, in Dr. Fleischmann’s opinion.

Which is more effective: a Jakinib or a tumor necrosis factor inhibitor?

Only one clinical trial has addressed this question with sufficient power to yield a statistically significant answer. This was the RA-BEAM trial presented at the 2015 ACR meeting. RA-BEAM was a randomized head-to-head study of baricitinib plus methotrexate versus adalimumab plus methotrexate in 1,305 methotrexate inadequate responders. Baricitinib was the clear winner, with week 24 ACR 20 and ACR 50 responses of 70% and 45%, respectively, compared with 61% and 35% for adalimumab. Particularly impressive was baricitinib’s outperformance of adalimumab on the pain component of the ACR score.

“This is the first study to show a Jakinib plus methotrexate is actually superior to a TNF inhibitor plus methotrexate. And adalimumab is a really, really good drug. Is it a big difference? It’s not tremendous, but it’s a difference. Is it clinically significant? In that extra 9%-10% of patients, it obviously is; in most it’s probably not,” Dr. Fleischmann said.

Will an oral Jakinib be the first drug physicians prescribe in rheumatoid arthritis patients, or the last?

“The data so far shows that Jakinib monotherapy is very viable, as opposed to biologic monotherapy, which is viable but less so. RA-BEAM showed baricitinib was superior to a TNF inhibitor, and there are studies to suggest but don’t prove that tofacitinib is, too,” he said.

Dr. Fleischmann reported serving as a paid researcher for and/or consultant to numerous pharmaceutical companies, including most of those developing Jakinibs.

bjancin@frontlinemedcom.com