	You are a member of your local dermatologic society and attend monthly meetings in order to obtain CME credits. In order to finance the meeting and encourage attendance, the society has the monthly meetings financed by a prominent drug company.

	The drug company provides journal articles documenting the off-label use of one of their prescription pharmaceutical agents. You obtain CME credits, read the journal article and begin prescribing the off-label medication. Is the drug company in violation of the U.S. Food and Drug Administration (FDA) rulings? Are your actions acceptable?

	The FDA derives its authority to regulate various aspects of the pharmaceutical industry from the Federal Food, Drug and Cosmetic Act, United

	States Code, Title 21 section 301. For a prescription drug to be distributed by a manufacturer in interstate commerce, the manufacturer is required to demonstrate that the drug is both safe and effective for its intended uses.

	As part of the approval process, FDA also reviews the proposed labeling for the drug, which includes all proposed claims about the drug’s risks and benefits. Labeling encompasses all written, printed or graphic material upon any drug or any of its containers or wrappers; or, all written, printed or graphic material accompanying the drug.

	The most obvious form of labeling is the package insert that accompanies the drug, but the term has also been construed to include nearly every form of drug company promotional activity, including booklets, mailing pieces, bulletins and literature that supplements, explains, or is textually related to the product.

	FDA will only approve the company’s new drug application if the labeling conforms to FDA-approved uses. In 1962, Congress determined that a manufacturer seeking to market or promote a product for an unlabeled use must resubmit the drug for another series of clinical trials similar to those from the initial approval.

	Off-label uses include treating a condition not indicated on the label, or treating the indicated condition but varying the dosage regimen or even the patient population. Manufacturer promotion of off-label uses constitutes misbranding and is in violation of the FDA statutes. Physicians are not held to the same standard as manufacturers. Once a drug has been approved by

	FDA for marketing for any use, the prescription choices are left to the discretion of the physician. A dermatologist may prescribe an approved drug for any medical condition regardless of whether FDA has determined that the drug is safe and effective with respect to that illness.

	Since off-label uses are presently an accepted aspect of a dermatologist’s prescribing regimen, the open dissemination of scientific and medical information regarding these treatments is of great-import. The FDA acknowledges that physicians need reliable and up-to-date information concerning of -label uses. FDA recognizes that sources for such information are varied, and include CME lectures and seminars. It specifically recognizes that the need for reliable information is particularly acute in the off–label treatment arena because the primary source of information usually available to physicians, such as the FDA approved label, is absent.

	Off-label prescription practices can be problematic and have proven harmful. Therefore, the FDA, consistent with its mission to protect the public health, has been charged to develop guidelines.

	In the late 1980s drug companies greatly increased their resources devoted to sponsoring CME seminars. Concerns about drug manufacturer promotional practices caught the attention of Congress. Among the issues was manufacturer promotion of unapproved claims for approved products.

	Following Congressional hearings, FDA sought to distinguish between situations in which CME was “independent of the substantive influence of the supporting company,” and therefore not subject to regulation, as opposed to situations when the manufacturers are in a position to influence the presentation of information.

	The FDA developed twelve factors to consider in evaluating programs and activities to determine “independence,” which include:

		Who controls the content and selects the presenters and the moderator;

		Whether there is meaningful disclosure as to the companies funding and whether unapproved uses will be discussed;

		The focus of the program, such as whether the central theme is on of -label product;

		The relationship between supporting companies and the CME provider;

		Opportunities for meaningful discussion and questioning; Dissemination of information;

		Complaints raised by the provider, presenters or attendees regarding attempts by the supporting company to influence content.

	Additionally, while not required, a written agreement between the meeting provider and the supporting company can provide valuable evidence that the sponsoring company will not control the CME content, and that the meeting provider is solely responsible for conducting the activity.

	In 1996, FDA issued a second set of guidelines concerning the distribution of “enduring” materials.

	These include textbook excerpts and article reprints from medical and scientific journals.

	These guidelines restrict manufacturer distribution of enduring materials when the publications address of -label uses for the company’s previously approved products. This would even include a publication from a peer-reviewed journal.

	FDA allows manufacturers to disseminate reprints from journal articles but requires that the principal subject of the article should be the uses approved by FDA. This ruling, on its face, would prohibit manufacturer distribution of the aforementioned journal articles at the monthly dermatology meeting.

	In Washington Legal Foundation v. Michael A. Friedman, Commissioner, Food and Drug Administration and Donna Shalala, Secretary of U.S. Dep’t of Health and Human Services, the Washington Legal Foundation, a non-profit public interest law and policy center that defends the rights and individuals and businesses to go about their affairs without undue influence from government regulators, contended that journal articles - as scientific and academic speech - are entitled to the highest level of First Amendment free speech protection. There should be no FDA restrictions on the dissemination of such materials. FDA claimed that journal articles represent commercial speech that is not as strictly protected by the First Amendment, as is non-commercial speech.

	The United States District Court for the District Court of Columbia, in analyzing the litigation, noted that the distribution of enduring materials and sponsorship of CME seminars does constitute speech and therefore is entitled to First Amendment protection.

	The Court struggled with whether manufacturer distribution of peer reviewed articles promoting off-label uses at CME seminars was pure speech, demanding near absolute free speech protection, or commercial speech which could be somewhat restricted. In its decision in July of 1998, the Court noted that when considered outside the context of manufacturer product promotion, CME seminars, peer-reviewed articles and commercially available medical textbooks merit the highest degree of constitutional protection.

	The question raised was whether speech that would be fully protected as scientific and/or educational speech can be transformed into commercial speech, with a lesser degree of free speech protection, simply because a commercial entity seeks to distribute materials that would lead to an increase in sales of the product addressed in the speech. Such restrictions might be appropriate when public health is an issue.

	The court looked at the U.S. Supreme Court decision in Bolger v. Youngs Drug Products Corp.

	The Supreme Court found it hard to fathom how dissemination of enduring materials or sponsorship of CME seminars could constitute a deceptive

	or aggressive sales practice. After all, physicians may obtain the same information from other sources. However, the Court noted that for any given off-label treatment, there may be a wide variety of scientific research data available, some of which concludes that the off-label treatment is effective, some of which concludes it is not. The manufacturers will likely only seek to disseminate information that presents their product in a favorable light. Because of manufacturers significant financial resources, distribution of favorable articles is more likely than those showing unfavorable results. Thus, the Court decided that of -label articles, such as a peer-reviewed journal publication, represent commercial speech when distributed by a drug manufacturer at a monthly CME dermatology meeting.

	The court then evaluated whether FDA’s ban of manufacturer’s distribution of of -label peer reviewed articles was appropriate and felt the absolute ban was more restrictive than necessary. All that should be required is “full, complete, and unambiguous disclosure by the manufacturer.” Such disclosure, advising physicians that FDA has not approved such use of the drug, avoids dissemination of potentially misleading information.

	This requirement would still lead manufacturers to seek FDA labeling approval so as to allow broader distribution of the currently “of -label” drug. The court noted that in the balancing act between free speech and restriction of First Amendment rights, it is always better to allow free speech.

	The court would have no difficulty with the distribution of off-label journal articles as long as the drug manufacturer provides full disclosure.

	The First Amendment right of speech can be protected while at the same time the public at large is not placed in danger. Finally, dermatologists are not in violation of FDA statutes for prescribing the of -label use of prescription drugs.

Articles

In a CME session through your local dermatology society, a prominent drug company provides journal articles documenting the off-label use of one of their prescription pharmaceutical agents. You obtain CME credits, read the journal article and begin prescribing the off-label medication. Is the drug company in violation of the U.S. Food and Drug Administration (FDA) rulings? Are your actions acceptable?

I prescribe drugs off-label. Am I in violation of FDA regulations

	I have recently returned from the American Academy of Dermatology annual meeting in San Diego. Based on the quality of the presentations, the exciting new innovations discussed and the frank, yet upbeat assessments about the future of our specialty, I am once again fired up about being a dermatologist.

	I would like to share a number of new ideas and therapeutic pearls that were presented at the meeting. This will be a small fraction of the information presented, but represents the portion of dermatology that is of most interest to me.

		Drs. Gregor Jamec and Haley Naik discussed the difficulties in managing hidradenitis suppurativa (HS). One potentially useful agent in severe and recalcitrant disease is adalimumab (Humira, Abbvie), which is approved for this indication. It is only of modest benefit and must be given weekly. The main problem is the fixed dose, which makes it less likely that obese patients (as many are with HS) get an amount that is probably too low to be of benefit. A good alternative could be infliximab (Remicade, Janssen) where dosage can be modified by weight to achieve the maximum benefit.
		 

		Dr. Eric Simpson discussed the controversies surrounding the treatment of atopic dermatitis.It appears that bleach baths are no better than regular baths in improving skin. Bathing or showering maximizes the efficacy of topical corticosteroids when applied immediately after. Emollients remain the keystone of eczema control by helping to repair a chronically inadequate anatomic skin barrier.
		 

		Dr. April Armstong gave a primer on evaluating clinical studies, specifically those with data based on long-term follow-ups. If the data are presented as “as observed,” test subjects that drop out before the end of the study period are not counted. Many of these subjects may have quit prematurely because of a treatment failure. Thus the “observed” data would be overly optimistic. At the other end of the spectrum, if all dropouts are considered failures, the conclusions might be too pessimistic. We need to be vigilant about how data are presented.

Dr. Armstrong also discussed the subject of inflammatory bowel disease (IBD) and biologic drug use. In patients with psoriasis and associated IBD, TNF inhibitors or IL-23 inhibitors are the best choices.

		Dr. Carolyn Bangert reviewed azathioprine and its value in the treatment of skin disease. The drug should be used only after a Thiopurine S-methyltransferase (TPMT) level is determined. In the rare (1 in 300) patient who lacks any enzyme activity, azathioprine should not be used at all. The drug should be started at a dose of 2.5 mg/kg/day and titrated as per the response and side effect profile. One should allow 6-8 weeks before making a definative determination about its effectiveness. There is a running controversy about whether azathioprine causes hepatosplenic lymphoma. This is probably not an important issue in dermatologic patients since it occurs almost exclusively in those treated for Crohn disease for greater than three years. Skin cancer after long-term use is a potential concern, however.

		One of my favorite bits of advice came from Dr. Jeanette Jakus who described two products used as “counter-stimulants” during injections. These are most useful in children but can also be valuable in needle-phobic adults.

They are “Buzzy Mini Personal Striped” and “Shot Blocker,” both of which can be purchased through a major online retailer. The contact points from these devices saturate the local sensory nerves, thus distracting the patient from injection pain signals.
		 

		Dr. John Koo discussed one of our most vexing management problems: The patient with delusions of parasitosis. Although several anti-psychotic drugs have been used in this condition, pimozide (Orap, Teva Pharmaceuticals) remains the treatment of choice for one important reason: The only indication in the packet insert for this medication is Tourette’s syndrome, a purely neurologic condition. Thus, the patient is not stigmatized with the fact that he is taking a medication used in psychotic individuals. A dose of 3-5 mg per kg body weight is usually sufficient to achieve a complete remission. By starting at 1-2 mg per day and titrating upward over several weeks, the side ef ects can be largely mitigated. Checking for possible arrhythmias is almost certainly not necessary at the low doses used for this condition.
		 

		Dr. Mark Lebwohl revisited the biologic agents and highlighted the advantages of the various products. Adalimumab and the other TNF inhibitors may actually help to prevent myocardial infarctions by reducing systemic inflammation. Secukinumab (Cosentyx, Novartis) may induce a remission which could last 1-2 years after the drug is discontinued.

Brodalumab (Siliq, Ortho Dermatologics) is perhaps the fastest acting biologic agent available today. Ixekinumab (Taltz, Eli Lily) is now indicated for both psoriasis and psoriatic arthritis. Ustekinumab (Stelara, Janssen) is now approved for use in adolescents and may be a good agent in this group because fewer injections per year are needed. Guselkumab (Tremfya, Janssen) may be the most ef ective drug for psoriasis, although it is a little slower acting than others. Apremilast (Otezla, Celgene) is a good alternative for those with more moderate disease.

	Perhaps the most inspiring talk given at the meeting was by Dr. Abraham Verghese who is an internist and the author of the best-selling book, “Cutting For Stone.” He discussed the erosion of physician and patient satisfaction over the past 10-15 years and traced it, in part, to the situation where patients are no longer actually being examined, but rather their medical records are combed exhaustively in search of correct diagnoses. This inevitably leads to a deterioration in the doctor-patient relationship. However, he sees our specialty as one where the so-called old fashioned virtue of direct examination, including a detailed history and complete cutaneous examination, which includes actually touching the person, still prevails. I left that lecture and the meeting itself feeling very good about dermatology.

In this article, Dr. Norman Levine sums up his takeaways from the American Academy of Dermatology annual meeting, beginning with a presentation by two physicians who addressed the difficulties of managing hidradenitis suppurativa, such as fixed dosing. He also addressed controversies associated with treatments for atopic dermatitis. Apparently, bleach baths are no better than regular baths in improving skin symptoms.

AAD insights and takeaways

	“While the hypothesis still needs to be proven specifically in a psoriasis population, the data convincingly argues for tighter disease control in patients with psoriasis.”                                  Alexander Egeberg, M.D., Ph.D.

	It has become clear in the past two decades that psoriasis has transitioned from being a mere skin condition to a disease with systemic implications, says Alexander Egeberg, M.D., Ph.D., a physician with the University of Copenhagen Herlev and Gentofte Hospital in Denmark.  

	“Patients with psoriasis have an increased incidence and prevalence of cardiovascular risk factors, including obesity, hyperlipidemia, hypertension, diabetes and cardiovascular events, including myocardial infarction and stroke. Moreover, psoriasis significantly impairs patients’ quality of life, and the risk of depression and anxiety disorders is increased in our patients,” Dr. Egeberg said during a 

 on Feb. 16 during the American Academy of Dermatology annual meeting in San Diego.  

	Data suggest that plaque psoriasis may be a risk factor for cardiovascular disease and the development of diabetes, he said citing an observational 

 he published last year on the relationship between psoriasis duration, vascular inflammation and cardiovascular events. Dr. Egeberg and colleagues found that psoriasis duration had detrimental effects on vascular inflammation and major adverse cardiovascular events, suggesting that cumulative duration of exposure to low-grade chronic inflammation might speed vascular disease development and the occurrence of major adverse cardiovascular events. Providers should consider asking psoriasis patients about disease duration in order to determine whether counselling for increased cardiovascular disease risk is needed, they concluded.

Journal of the American Academy of Dermatology

, researchers measured psoriasis severity on type 2 diabetes mellitus risk. They found that type 2 diabetes was more likely in patients with severe psoriasis - psoriasis impacting more than 10 percent of their body surface area. Dermatologists and other clinicians who care for psoriasis patients could refer to body surface area measurements to target diabetes prevention efforts among those patients, the authors concluded.

	In very recent years, there has been an increased in comorbidities that share genetic and inflammatory pathways; in particular, inflammatory bowel disease, such as Crohn's disease and ulcerative colitis, Dr. Egeberg said.

 on the association between psoriasis and inflammatory bowel disease, published in 2016, Dr. Egeberg and colleagues observed that psoriasis is associated with increased risks for Crohn disease and ulcerative colitis, with the association increasing with psoriasis severity. They also observed an increased risk of psoriasis in patients with inflammatory bowel disease, which suggests the need to focus on gastrointestinal symptoms in patients with psoriasis, according to the study.

	“Such findings are of particular importance since some drugs may be effective in treating not only psoriasis, but also some of the associated comorbidities, while other drugs may aggravate or induce such comorbidities,” he says.

	For example, Dr. Egeberg says recent advances in cardiology have shown that targeted dampening of inflammation - independent of cholesterol levels - significantly reduces the risk of myocardial infarction.

 published last year in the New England Journal of Medicine in which researchers found that anti-inflammatory therapy targeting the interleukin-1β innate immunity pathway with the drug canakinumab significantly lowered the rate of recurrent cardiovascular events compared to placebo, regardless of lipid-level lowering.

	“While the hypothesis still needs to be proven specifically in a psoriasis population, the data convincingly argues for tighter disease control in patients with psoriasis,” Dr. Egeberg says. “For dermatologists, it may be relevant to do an annual screening for traditional cardiovascular risk factors - hypertension, diabetes, high cholesterol, smoking - in patients with psoriasis, and referral to either a general practitioner or a cardiologist may be relevant in those deemed at high risk of cardiovascular disease. Moreover, since inflammatory bowel disease may be present more frequently in patients with psoriasis, gastrointestinal symptoms in these patients may warrant further investigations by a gastroenterologist.”

	Dr. Egeberg has received research funding from Pfizer, Eli Lilly, the Danish National Psoriasis Foundation, and the Kgl Hofbundtmager Aage Bang Foundation, and honoraria as consultant and/or speaker from Leo Pharma, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly, Novartis, Galderma, and Janssen Pharmaceuticals.

“F012 - Psoriasis and Atopic Dermatitis: Advances in Therapy and Comorbidities

,” American Academy of Dermatology 2018 annual meeting. Egeberg, Alexander Egeberg, John Koo, Jonathan I. Silverberg, et al. 9-11 a.m., Friday, February 16.

	Egeberg A, Skov L, Joshi AA, et al. “The relationship between duration of psoriasis, vascular inflammation, and cardiovascular events.” 

. October 2017. DOI: 10.1016/j.jaad.2017.06.028..

	Wan MT, Shin DB, Hubbard RA, Noe MH, Mehta NN, Gelfand JM. “Psoriasis and the risk of diabetes: A prospective population-based cohort study.” 

. February 2018. DOIoi: 10.1016/j.jaad.2017.10.050.

	Egeberg A, Mallbris L, Warren RB, et al. “Association between psoriasis and inflammatory bowel disease: a Danish nationwide cohort study.” 

. September 2016. DOI: 10.1111/bjd.14528.

	Ridker PM, Everett BM, Thuren T, et al. “Anti-inflammatory Therapy with Canakinumab for Atherosclerotic Disease.” 

. September 2017. DOI: 10.1056/NEJMoa1707914. 

Mounting clinical evidence points to a need for tighter disease control in psoriasis patients, says Dr. Alexander Egeberg.

The evolution of psoriasis from skin to heart disease

	Dermatologists should take ownership of screening patients for mental health concerns associated with their skin condition.

	Skin conditions can lead to psychiatric disorders in 30 percent of patients, particularly adolescents, patients being treated for facial lesions and scars, patients suffering from insomnia or patients with severe or recalcitrant skin disease, wrote the authors of a Viewpoint article in 

	“When the psychiatric concern is related to skin disease, dermatologists are in a unique position to identify the problem and help patients seek treatment,” wrote the authors who were led by Mohammad Jafferany, M.D., of Central Michigan University.

	In dermatology, there are psychiatric conditions can fall into one of two categories:  primary or secondary. Primary skin conditions include disorders of self-induced skin lesions due to an underlying emotional disturbance, such as acne excoriee. Secondary psychiatric disorders, such as depression, usually arise as a result of a primary health condition, such as severe psoriasis.

	“When these dermatologic-specific risk factors are paired with additional high-risk features, depression and suicidal ideation screening become increasingly necessary,” the authors wrote.

	Symptoms should be tracked and documented, the authors suggest. “We recommend that dermatologists maintain an appropriate index of suspicion for psychiatric disease, apply brief standardized mental health questionnaires, and refer patients to appropriate services when needed,” the authors wrote.

	Dermatologists do not always follow-up appropriately when they do identify mental health problems in a patient consultation. “It is unclear if this is owing to lack of clear guidelines, lack of time in busy clinics, or the perception that secondary psychiatric disorders fall outside of the dermatology domain,” the authors wrote.

	Some dermatologists may have difficulty perceiving a patient’s psychological distress, and may feel uncertain regarding psychiatric diagnoses, particularly in patients that may not volunteer mental health information in a dermatology visit.

	The Patient Health Questionnaire-2 (PHQ-2) is a recommended resource that may help identify patients. Questions include:

	1.      Over the past 2 weeks, how often have you been bothered by (a) little interest or pleasure in doing things or (2) feeling down, depressed, or hopeless.

	2.      To gauge whether an immediate follow-up is necessary, “Do you ever think about ending your own life?”  If so, do you currently have a plan to commit suicide?”

	Katherine McDonald, BScH; Amanda Shelley, BScH; Mohammad Jafferany, MD, FAPA. “The PHQ-2 in Dermatology-Standardized Screening for Depression and Suicidal Ideation,” Dec. 27, 2017. 

	Kroenke K, Spitzer RL, Williams JBW. “The Patient Health Questionnaire-2: validity of a two-item depression screener,” Nov. 2003. 

 Nov. 2003. DOI:10.1097/01.MLR.0000093487.78664.3C

	Connor CJ. “Management of the psychological comorbidities of dermatological conditions,” Apr. 20, 2017. 

Clinical, Cosmetic and Investigational Dermatology.

Dermatologists should take ownership of screening patients for mental health concerns associated with their skin condition.

Dermatologists fail to screen patients for depression

Dermatomyositis (DM) is a rare autoimmune disease characterized by varying degrees of skin disease and proximal muscle inflammation. At least a fifth of patients have clinically amyopathic DM so present with skin disease without muscular weakness or evidence of myositis.

The skin symptoms of DM are often the most debilitating and the most challenging to treat and can significantly impair quality of life, but there is a lack of strong evidence for the use of most agents and little knowledge about the longitudinal course of the disease.

A study published in the December issue of “

International Journal of Women's Dermatology”

 finds that second-line agents need to be incorporated into treatment for moderate to severe dermatomyositis, which is otherwise very difficult to treat.

“The results show that management of cutaneous DM often requires second-line agents because anti-malarial medications alone are insufficient to treat most patients with skin-only disease,” researchers wrote.

A group of researchers at the University of Pennsylvania, Philadelphia assessed the impact of care delivered using a treatment algorithm to determine systemic treatment for 41 patients with skin only DM - those with clinically amyopathic DM and no lung involvement - seen at a center between July 2009 and April 2013.

Anti-malarial medication is first line therapy for DM where skin symptoms predominate, and most were initiated on hydroxychloroquine (HCQ) ≤6.5 mg/kg/day for 8 weeks. Quinacrine 100 mg/day was added if a trial of HCQ was ineffective, and chloroquine ≤3.5mg/kg/day was used instead of HCQ in patients in whom HCQ was ineffective or who had experienced a reaction to it previously.

A second line agent such as methotrexate (MTX), mycophenolate mofetil (MMF), or azathioprine (AZA) was added if symptoms progressed despite use of antimalarial agents, and if adequate control was not achieved within another 8 weeks, patients were switched to another cytotoxic agent. Use of IVIg, at 2 g/kg administered over two to five days each month, was considered in patients who still did not respond, followed by oral calcineurin inhibitors.

Systemic corticosteroid medications were not used routinely but a course of medium-to-high dose corticosteroid medications was used to provide relief in cases of severe disease. Topical agents such as corticosteroid or immunomodulator medications were commonly used by participants.

Twenty-three of the patients (56.1%) received antimalarial medications alone and 18 patients (43.9%) received second- or third-line agents (cytotoxic drugs or IVIg treatment in combination with antimalarial medications).

Ten patients used HCQ alone (24.4%), 22.0% used HCQ and quinacrine, 4.9% chloroquine, and 2.4% chloroquine and quinacrine. Although 24.4% of patients were managed with HCQ alone, the researchers highlight that this is an overestimation of the efficacy of HCQ monotherapy, because four of the ten patients had quinacrine prescribed on their very last study visit.

Just 14.6% of patients with skin-only disease were managed with HCQ alone, which suggests that HCQ is less effective in the treatment of patients with cutaneous DM than patients with cutaneous lupus erythematosus, the researchers say.

Initial disease severity and outcomes were assessed using the Cutaneous Dermatomyositis Disease Area and Severity Index. After a median duration of treatment of 24 months, the median final CDASI score for all patients with skin-only disease was 13.5.  Most patients did not experience complete resolution of skin symptoms and had at least mild disease activity at the time of their final visit.

Eleven of the patients (26.8%) received prednisone which may have contributed to clinical improvements and changes in CDASI activity scores.

Prospective trials have reported a significant improvement in cutaneous DM symptoms with IVIg treatment, and good results were seen in the small number of most refractory patients treated with IVIg in the University of Pennsylvania study. However, the researchers point out that since patients with a more severe disease status received escalating therapy, it was difficult to compare final CDASI scores across treatment groups and that clinical trials are needed to assess the efficacy of agents alone or in combination with others.

The same researchers looked in detail at the course of the skin only DM treated according to the algorithm in 40 patients who had their CDASI activity recorded for at least 2 years.

Sixteen patients began the study with mild disease and 24 with moderate to severe disease.

More patients with moderate-severe disease (n=19, 79.2%) experienced an improvement in disease activity compared to those with mild disease (n=2, 12.5%) in whom the disease was more likely to remain stable (n=10, 62.5%) than in those with moderate-severe disease (n=2, 8.3%). The variability of disease activity (flares/year) was nearly identical with 87.5% of patients with mild disease and 79% of patients with moderate-severe disease experienced waxing and waning of disease activity.

The researchers suggest that there may be a “floor effect,” meaning it is harder to see a significant change in CDASI score when starting with mild disease and that clinicians may offer less aggressive treatment options to milder patients resulting in less therapeutic benefit.

Researcher Dr Victoria Werth says: “Better treatments are needed for both moderate/severe and mild disease, since current treatments are relatively toxic and don’t always work. With relatively new disease severity tools that measure the skin (CDASI) it is now possible to assess new therapeutics using the skin as a window.  This is a very exciting time for developing rationale new therapeutics for dermatomyositis.”

The Cutaneous Dermatomyositis Disease Area and Severity Index was initially developed and validated to enable dermatologist to assess the impact of therapy on cutaneous manifestations in DM. Quantifying skin disease activity can offer early insight into the relative efficacy of treatment in clinical practice and research trials, Dr Werth’s research group has shown that other specialties, including rheumatology and neurology, “who do not regularly evaluate cutaneous DM are capable of using the CDASI effectively”

In terms of potential new treatments, Dr Werth’s group has just completed a single centre NIH-funded phase 2 randomized, placebo-controlled trial of skin predominant dermatomyositis with a nonpsychoactive cannabinoid called lenabasum - the first placebo controlled randomized trial for skin-predominant disease.  The results, presented at the American College of Rheumatology meeting in November, showed that patients on active drug demonstrated greater improvement in disease activity and several measurements of quality of life, and that the drug was well tolerated. A larger study is now in the planning stages

Other treatments being evaluated include IVIg, Tofacitinib (a JAK inhibitor), CTLA4Ig (inhibits T cell activation), and novel approaches related to intervening pathways known to be activated in dermatomyositis, Dr Werth says.

i. Anyanwu CO, Chansky PB, Feng R, Carr K, Okawa J, Werth VP. The systemic management of cutaneous dermatomyositis: Results of a stepwise strategy. International Journal of Women's Dermatology 2017; 3: 189–194.

ii. Chansky PB, Olazagasti J M, Feng R, Werth VP. Cutaneous dermatomyositis disease course followed over time using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI). Journal of the American Academy of Dermatology DOI 10.1016/j.jaad.2017.10.022

iii. Tiao J, Feng R, Bird S, Choi J K, Dunham J, George M, Gonzalez-Rivera TC et al. The reliability of the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) among dermatologists, rheumatologists and neurologistsBr J Dermatol 2017;176(2):423-430. DOI 10.1111/bjd.15140

Study finds that second-line agents need to be incorporated into treatment for moderate to severe dermatomyositis, which is otherwise very difficult to treat.

Vol. 39 No. 03

I prescribe drugs off-label. Am I in violation of FDA regulations

AAD insights and takeaways

The evolution of psoriasis from skin to heart disease

Dermatologists fail to screen patients for depression

Dermatomyositis requires a second-line treatment