Psoriasis

VIENNA – Updated longer-term safety data for ixekizumab in patients with moderate to severe plaque psoriasis continue to show no new safety signals, Alexa B. Kimball, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The safety database now includes 4,213 psoriasis patients on ixekizumab (Taltz) for a total of 7,843 patient-years of regular ongoing follow-up in seven different phase I-III clinical trials. And with a large group of patients now having been on the novel humanized monoclonal antibody targeting interleukin-17A for 2 years and smaller numbers out to 5 years, there have been no surprises, according to Dr. Kimball, professor of dermatology at Harvard Medical School, Boston.

bjancin@frontlinemedcom.com

VIENNA – Updated longer-term safety data for ixekizumab in patients with moderate to severe plaque psoriasis continue to show no new safety signals, Alexa B. Kimball, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The safety database now includes 4,213 psoriasis patients on ixekizumab (Taltz) for a total of 7,843 patient-years of regular ongoing follow-up in seven different phase I-III clinical trials. And with a large group of patients now having been on the novel humanized monoclonal antibody targeting interleukin-17A for 2 years and smaller numbers out to 5 years, there have been no surprises, according to Dr. Kimball, professor of dermatology at Harvard Medical School, Boston.

bjancin@frontlinemedcom.com

VIENNA – Updated longer-term safety data for ixekizumab in patients with moderate to severe plaque psoriasis continue to show no new safety signals, Alexa B. Kimball, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The safety database now includes 4,213 psoriasis patients on ixekizumab (Taltz) for a total of 7,843 patient-years of regular ongoing follow-up in seven different phase I-III clinical trials. And with a large group of patients now having been on the novel humanized monoclonal antibody targeting interleukin-17A for 2 years and smaller numbers out to 5 years, there have been no surprises, according to Dr. Kimball, professor of dermatology at Harvard Medical School, Boston.

bjancin@frontlinemedcom.com

At the 19th Annual Mount Sinai Winter Symposium, Dr. Jashin J. Wu spoke about psoriasis and internal disease. He discussed psoriasis and noncardiovascular comorbidities as well as cardiovascular comorbidities. Dr. Wu also addressed if treating psoriasis can improve cardiovascular disease.

At the 19th Annual Mount Sinai Winter Symposium, Dr. Jashin J. Wu spoke about psoriasis and internal disease. He discussed psoriasis and noncardiovascular comorbidities as well as cardiovascular comorbidities. Dr. Wu also addressed if treating psoriasis can improve cardiovascular disease.

At the 19th Annual Mount Sinai Winter Symposium, Dr. Jashin J. Wu spoke about psoriasis and internal disease. He discussed psoriasis and noncardiovascular comorbidities as well as cardiovascular comorbidities. Dr. Wu also addressed if treating psoriasis can improve cardiovascular disease.

Psoriasis is a common dermatologic problem with nearly 5% prevalence in the United States. There is a bimodal distribution with peak onset between 20 and 30 years of age and 50 and 60 years, which means that this condition can arise before, during, or after military service.¹ Unfortunately, for many prospective recruits psoriasis is a medically disqualifying condition that can prevent entry into active duty unless a medical waiver is granted. For active-duty military, new-onset psoriasis and its treatment can impair affected service members’ ability to perform mission-critical work and can prevent them from deploying to remote or austere locations. In this way, psoriasis presents a unique challenge for active-duty service members.

Many therapies are available that can effectively treat psoriasis, but these treatments often carry a side-effect profile that limits their use during travel or in austere settings. Herein, we discuss the unique challenges of treating psoriasis patients who are in the military at a time when global mobility is critical to mission success. Although in some ways these challenges truly are unique to the military population, we strongly believe that similar but perhaps underappreciated challenges exist in the civilian sector. Close examination of these challenges may reveal that alternative treatment choices are sometimes indicated for reasons beyond just efficacy, side-effect profile, and cost.

Treatment Considerations

The medical treatment of psoriasis has undergone substantial change in recent decades. Before the turn of the century, the mainstays of medical treatment were steroids, methotrexate, and phototherapy. Today, a wide array of biologics and other systemic drugs are altering the impact of psoriasis in our society. With so many treatment options currently available, the question becomes, “Which one is best for my patient?” Immediate considerations are efficacy versus side effects as well as cost; however, in military dermatology, the ability to store, transport, and administer the treatment can be just as important.

Although these problems may at first seem unique to active-duty military members, they also affect a substantial segment of the civilian sector. Take for instance the government contractor who deploys in support of military contingency actions, or the foreign aid workers, international businessmen, and diplomats around the world. In fact, any person who travels extensively might have difficulty carrying and storing their medications (Table) or encounter barriers that prevent routine access to care. Travel also may increase the risk of exposure to virulent pathogens such as Mycobacterium tuberculosis, which may further limit treatment options. This group of world travelers together comprises a minority of psoriasis patients who may be better treated with novel agents rather than with what might be considered the standard of care in a domestic setting.

Options for Care

Methotrexate

In many ways, methotrexate is the gold standard of psoriasis treatment. It is a first-line medication for many patients because it is typically well tolerated, has well-established efficacy, is easy to administer, and is relatively inexpensive.¹² Although it is easy to store, transport, and administer, it requires regular laboratory monitoring at 3-month intervals or more frequently with dosage changes. It also is contraindicated in women of childbearing age who plan to become pregnant, which can be a considerable hindrance in the young active-duty population.

Cyclosporine

Cyclosporine is another inexpensive medication that can produce excellent results in the treatment of psoriasis.^1,12 Although long-term use of cyclosporine in transplant patients has been well studied, its use for the treatment of dermatologic conditions is usually limited to 1 year. The need for monthly blood pressure checks and at least quarterly laboratory monitoring means it is not an optimal choice for a deployed service member.

Acitretin

Acitretin is another systemic medication with an established track record in psoriasis treatment. Although close follow-up and laboratory monitoring is required for both males and females, use of this medication can have a greater effect on women of childbearing age, as it is absolutely contraindicated in any female trying to conceive.¹³ In addition, acitretin is stored in fat cells, and traces of the drug can be found in the blood for up to 3 years. During this period, patients are advised to strictly avoid pregnancy and are even restricted from donating blood.¹³ Given these concerns, acitretin is not always a reasonable treatment option for the military service member.

Biologics

Biologics are the newest agents in the treatment of psoriasis. They require less laboratory monitoring and can provide excellent results. Adalimumab is a reasonable first-line biologic treatment for some patients. We find the laboratory monitoring is minimally obtrusive, side effects usually are limited, and the efficacy is great enough that most patients elect to continue treatment. Unfortunately, adalimumab has some major drawbacks in our specific use scenario in that it requires nearly continuous refrigeration and is never to exceed 25°C (77°F), it has a relatively close-interval dosing schedule, and it can cause immunosuppression. However, for short trips to nonaustere locations with an acceptable risk for pathogenic exposure, adalimumab may remain a viable option for many travelers, as it can be stored at room temperature for up to 14 days.² Ustekinumab also is a reasonable choice for many travelers because dosing is every 12 weeks and it carries a lower risk of immunosuppression.^2,3 Ustekinumab, however, has the major drawback of high cost.¹² Newer IL-17A inhibitors such as secukinumab or ixekizumab also can offer excellent results, but long-term infection rates have not been reported. Overall, the infection rates are comparable to ustekinumab.^14,15 After the loading phase, secukinumab is dosed monthly and logistically could still pose a problem due to the need for continued refrigeration.¹⁴

Apremilast

Although it is not the best first-line treatment for every patient, apremilast carries 3 distinct advantages in treating the military patient population: (1) laboratory monitoring is required only once per year, (2) it is easy to store, and (3) it is easy to administer. However, the major downside is that apremilast is less effective than other systemic agents in the treatment of psoriasis.¹⁶ As with other systemic drugs, adjunctive topical treatment can provide additional therapeutic effects, and for many patients, this combined approach is sufficient to reach their therapeutic goals.

For these reasons, in the special case of deployable, active-duty military members we often consider starting treatment with apremilast versus other systemic agents. As with all systemic psoriasis treatments, we generally advise patients to return 16 weeks after initiating treatment to assess efficacy and evaluate their deployment status. Although apremilast may take longer to reach full efficacy than many other systemic agents, one clinical trial suggested this time frame is sufficient to evaluate response to treatment.¹⁶ After this initial assessment, we revert to yearly monitoring, and the patient is usually cleared to deploy with minimal restrictions.

Final Considerations

The manifestation of psoriasis is different in every patient, and military service poses additional treatment challenges. For all of our military patients, we recommend an initial period of close follow-up after starting any new systemic agent, which is necessary to ensure the treatment is effective and well tolerated and also that we are good stewards of our resources. Once efficacy is established and side effects remain tolerable, we generally endorse continued treatment without specific travel or work restrictions.

We are cognizant of the unique nature of military service, and all too often we find ourselves trying to practice good medicine in bad places. As military physicians, we serve a population that is eager to do their job and willing to make incredible sacrifices to do so. After considering the wide range of circumstances unique to the military, our responsibility as providers is to do our best to improve service members’ quality of life as they carry out their missions.

Psoriasis is a common dermatologic problem with nearly 5% prevalence in the United States. There is a bimodal distribution with peak onset between 20 and 30 years of age and 50 and 60 years, which means that this condition can arise before, during, or after military service.¹ Unfortunately, for many prospective recruits psoriasis is a medically disqualifying condition that can prevent entry into active duty unless a medical waiver is granted. For active-duty military, new-onset psoriasis and its treatment can impair affected service members’ ability to perform mission-critical work and can prevent them from deploying to remote or austere locations. In this way, psoriasis presents a unique challenge for active-duty service members.

Many therapies are available that can effectively treat psoriasis, but these treatments often carry a side-effect profile that limits their use during travel or in austere settings. Herein, we discuss the unique challenges of treating psoriasis patients who are in the military at a time when global mobility is critical to mission success. Although in some ways these challenges truly are unique to the military population, we strongly believe that similar but perhaps underappreciated challenges exist in the civilian sector. Close examination of these challenges may reveal that alternative treatment choices are sometimes indicated for reasons beyond just efficacy, side-effect profile, and cost.

Treatment Considerations

The medical treatment of psoriasis has undergone substantial change in recent decades. Before the turn of the century, the mainstays of medical treatment were steroids, methotrexate, and phototherapy. Today, a wide array of biologics and other systemic drugs are altering the impact of psoriasis in our society. With so many treatment options currently available, the question becomes, “Which one is best for my patient?” Immediate considerations are efficacy versus side effects as well as cost; however, in military dermatology, the ability to store, transport, and administer the treatment can be just as important.

Although these problems may at first seem unique to active-duty military members, they also affect a substantial segment of the civilian sector. Take for instance the government contractor who deploys in support of military contingency actions, or the foreign aid workers, international businessmen, and diplomats around the world. In fact, any person who travels extensively might have difficulty carrying and storing their medications (Table) or encounter barriers that prevent routine access to care. Travel also may increase the risk of exposure to virulent pathogens such as Mycobacterium tuberculosis, which may further limit treatment options. This group of world travelers together comprises a minority of psoriasis patients who may be better treated with novel agents rather than with what might be considered the standard of care in a domestic setting.

Options for Care

Methotrexate

In many ways, methotrexate is the gold standard of psoriasis treatment. It is a first-line medication for many patients because it is typically well tolerated, has well-established efficacy, is easy to administer, and is relatively inexpensive.¹² Although it is easy to store, transport, and administer, it requires regular laboratory monitoring at 3-month intervals or more frequently with dosage changes. It also is contraindicated in women of childbearing age who plan to become pregnant, which can be a considerable hindrance in the young active-duty population.

Cyclosporine

Cyclosporine is another inexpensive medication that can produce excellent results in the treatment of psoriasis.^1,12 Although long-term use of cyclosporine in transplant patients has been well studied, its use for the treatment of dermatologic conditions is usually limited to 1 year. The need for monthly blood pressure checks and at least quarterly laboratory monitoring means it is not an optimal choice for a deployed service member.

Acitretin

Acitretin is another systemic medication with an established track record in psoriasis treatment. Although close follow-up and laboratory monitoring is required for both males and females, use of this medication can have a greater effect on women of childbearing age, as it is absolutely contraindicated in any female trying to conceive.¹³ In addition, acitretin is stored in fat cells, and traces of the drug can be found in the blood for up to 3 years. During this period, patients are advised to strictly avoid pregnancy and are even restricted from donating blood.¹³ Given these concerns, acitretin is not always a reasonable treatment option for the military service member.

Biologics

Biologics are the newest agents in the treatment of psoriasis. They require less laboratory monitoring and can provide excellent results. Adalimumab is a reasonable first-line biologic treatment for some patients. We find the laboratory monitoring is minimally obtrusive, side effects usually are limited, and the efficacy is great enough that most patients elect to continue treatment. Unfortunately, adalimumab has some major drawbacks in our specific use scenario in that it requires nearly continuous refrigeration and is never to exceed 25°C (77°F), it has a relatively close-interval dosing schedule, and it can cause immunosuppression. However, for short trips to nonaustere locations with an acceptable risk for pathogenic exposure, adalimumab may remain a viable option for many travelers, as it can be stored at room temperature for up to 14 days.² Ustekinumab also is a reasonable choice for many travelers because dosing is every 12 weeks and it carries a lower risk of immunosuppression.^2,3 Ustekinumab, however, has the major drawback of high cost.¹² Newer IL-17A inhibitors such as secukinumab or ixekizumab also can offer excellent results, but long-term infection rates have not been reported. Overall, the infection rates are comparable to ustekinumab.^14,15 After the loading phase, secukinumab is dosed monthly and logistically could still pose a problem due to the need for continued refrigeration.¹⁴

Apremilast

Although it is not the best first-line treatment for every patient, apremilast carries 3 distinct advantages in treating the military patient population: (1) laboratory monitoring is required only once per year, (2) it is easy to store, and (3) it is easy to administer. However, the major downside is that apremilast is less effective than other systemic agents in the treatment of psoriasis.¹⁶ As with other systemic drugs, adjunctive topical treatment can provide additional therapeutic effects, and for many patients, this combined approach is sufficient to reach their therapeutic goals.

For these reasons, in the special case of deployable, active-duty military members we often consider starting treatment with apremilast versus other systemic agents. As with all systemic psoriasis treatments, we generally advise patients to return 16 weeks after initiating treatment to assess efficacy and evaluate their deployment status. Although apremilast may take longer to reach full efficacy than many other systemic agents, one clinical trial suggested this time frame is sufficient to evaluate response to treatment.¹⁶ After this initial assessment, we revert to yearly monitoring, and the patient is usually cleared to deploy with minimal restrictions.

Final Considerations

The manifestation of psoriasis is different in every patient, and military service poses additional treatment challenges. For all of our military patients, we recommend an initial period of close follow-up after starting any new systemic agent, which is necessary to ensure the treatment is effective and well tolerated and also that we are good stewards of our resources. Once efficacy is established and side effects remain tolerable, we generally endorse continued treatment without specific travel or work restrictions.

We are cognizant of the unique nature of military service, and all too often we find ourselves trying to practice good medicine in bad places. As military physicians, we serve a population that is eager to do their job and willing to make incredible sacrifices to do so. After considering the wide range of circumstances unique to the military, our responsibility as providers is to do our best to improve service members’ quality of life as they carry out their missions.

Psoriasis is a common dermatologic problem with nearly 5% prevalence in the United States. There is a bimodal distribution with peak onset between 20 and 30 years of age and 50 and 60 years, which means that this condition can arise before, during, or after military service.¹ Unfortunately, for many prospective recruits psoriasis is a medically disqualifying condition that can prevent entry into active duty unless a medical waiver is granted. For active-duty military, new-onset psoriasis and its treatment can impair affected service members’ ability to perform mission-critical work and can prevent them from deploying to remote or austere locations. In this way, psoriasis presents a unique challenge for active-duty service members.

Many therapies are available that can effectively treat psoriasis, but these treatments often carry a side-effect profile that limits their use during travel or in austere settings. Herein, we discuss the unique challenges of treating psoriasis patients who are in the military at a time when global mobility is critical to mission success. Although in some ways these challenges truly are unique to the military population, we strongly believe that similar but perhaps underappreciated challenges exist in the civilian sector. Close examination of these challenges may reveal that alternative treatment choices are sometimes indicated for reasons beyond just efficacy, side-effect profile, and cost.

Treatment Considerations

The medical treatment of psoriasis has undergone substantial change in recent decades. Before the turn of the century, the mainstays of medical treatment were steroids, methotrexate, and phototherapy. Today, a wide array of biologics and other systemic drugs are altering the impact of psoriasis in our society. With so many treatment options currently available, the question becomes, “Which one is best for my patient?” Immediate considerations are efficacy versus side effects as well as cost; however, in military dermatology, the ability to store, transport, and administer the treatment can be just as important.

Although these problems may at first seem unique to active-duty military members, they also affect a substantial segment of the civilian sector. Take for instance the government contractor who deploys in support of military contingency actions, or the foreign aid workers, international businessmen, and diplomats around the world. In fact, any person who travels extensively might have difficulty carrying and storing their medications (Table) or encounter barriers that prevent routine access to care. Travel also may increase the risk of exposure to virulent pathogens such as Mycobacterium tuberculosis, which may further limit treatment options. This group of world travelers together comprises a minority of psoriasis patients who may be better treated with novel agents rather than with what might be considered the standard of care in a domestic setting.

Options for Care

Methotrexate

In many ways, methotrexate is the gold standard of psoriasis treatment. It is a first-line medication for many patients because it is typically well tolerated, has well-established efficacy, is easy to administer, and is relatively inexpensive.¹² Although it is easy to store, transport, and administer, it requires regular laboratory monitoring at 3-month intervals or more frequently with dosage changes. It also is contraindicated in women of childbearing age who plan to become pregnant, which can be a considerable hindrance in the young active-duty population.

Cyclosporine

Cyclosporine is another inexpensive medication that can produce excellent results in the treatment of psoriasis.^1,12 Although long-term use of cyclosporine in transplant patients has been well studied, its use for the treatment of dermatologic conditions is usually limited to 1 year. The need for monthly blood pressure checks and at least quarterly laboratory monitoring means it is not an optimal choice for a deployed service member.

Acitretin

Acitretin is another systemic medication with an established track record in psoriasis treatment. Although close follow-up and laboratory monitoring is required for both males and females, use of this medication can have a greater effect on women of childbearing age, as it is absolutely contraindicated in any female trying to conceive.¹³ In addition, acitretin is stored in fat cells, and traces of the drug can be found in the blood for up to 3 years. During this period, patients are advised to strictly avoid pregnancy and are even restricted from donating blood.¹³ Given these concerns, acitretin is not always a reasonable treatment option for the military service member.

Biologics

Biologics are the newest agents in the treatment of psoriasis. They require less laboratory monitoring and can provide excellent results. Adalimumab is a reasonable first-line biologic treatment for some patients. We find the laboratory monitoring is minimally obtrusive, side effects usually are limited, and the efficacy is great enough that most patients elect to continue treatment. Unfortunately, adalimumab has some major drawbacks in our specific use scenario in that it requires nearly continuous refrigeration and is never to exceed 25°C (77°F), it has a relatively close-interval dosing schedule, and it can cause immunosuppression. However, for short trips to nonaustere locations with an acceptable risk for pathogenic exposure, adalimumab may remain a viable option for many travelers, as it can be stored at room temperature for up to 14 days.² Ustekinumab also is a reasonable choice for many travelers because dosing is every 12 weeks and it carries a lower risk of immunosuppression.^2,3 Ustekinumab, however, has the major drawback of high cost.¹² Newer IL-17A inhibitors such as secukinumab or ixekizumab also can offer excellent results, but long-term infection rates have not been reported. Overall, the infection rates are comparable to ustekinumab.^14,15 After the loading phase, secukinumab is dosed monthly and logistically could still pose a problem due to the need for continued refrigeration.¹⁴

Apremilast

Although it is not the best first-line treatment for every patient, apremilast carries 3 distinct advantages in treating the military patient population: (1) laboratory monitoring is required only once per year, (2) it is easy to store, and (3) it is easy to administer. However, the major downside is that apremilast is less effective than other systemic agents in the treatment of psoriasis.¹⁶ As with other systemic drugs, adjunctive topical treatment can provide additional therapeutic effects, and for many patients, this combined approach is sufficient to reach their therapeutic goals.

For these reasons, in the special case of deployable, active-duty military members we often consider starting treatment with apremilast versus other systemic agents. As with all systemic psoriasis treatments, we generally advise patients to return 16 weeks after initiating treatment to assess efficacy and evaluate their deployment status. Although apremilast may take longer to reach full efficacy than many other systemic agents, one clinical trial suggested this time frame is sufficient to evaluate response to treatment.¹⁶ After this initial assessment, we revert to yearly monitoring, and the patient is usually cleared to deploy with minimal restrictions.

Final Considerations

The manifestation of psoriasis is different in every patient, and military service poses additional treatment challenges. For all of our military patients, we recommend an initial period of close follow-up after starting any new systemic agent, which is necessary to ensure the treatment is effective and well tolerated and also that we are good stewards of our resources. Once efficacy is established and side effects remain tolerable, we generally endorse continued treatment without specific travel or work restrictions.

We are cognizant of the unique nature of military service, and all too often we find ourselves trying to practice good medicine in bad places. As military physicians, we serve a population that is eager to do their job and willing to make incredible sacrifices to do so. After considering the wide range of circumstances unique to the military, our responsibility as providers is to do our best to improve service members’ quality of life as they carry out their missions.

How does psoriatic arthritis present?

Psoriatic arthritis (PsA) can present in psoriasis patients with an average latency of approximately 10 years. In patients with a strong genetic predisposition, another more severe form of PsA can present earlier in life (<20 years of age). Although PsA generally is classified as a seronegative spondyloarthropathy, more than 10% of patients may in fact be rheumatoid factor-positive. Nail pitting is a feature that can suggest the possibility of PsA, present in almost 90% of patients with PsA.

Who should treat PsA?

Although involving our colleagues in rheumatology is usually beneficial for our patients, in most cases dermatologists can and should effectively manage the care of PsA. The immunology of PsA is the same as psoriasis, which contrasts with rheumatoid arthritis (RA). Although active human immunodeficiency virus infection can trigger widespread psoriasis and PsA, RA conversely improves with the depletion of CD4+ cells. Methotrexate, which is used cavalierly by rheumatologists for RA, has a different effect in psoriasis; liver damage is 3 times as likely in psoriasis versus RA at the same doses, while cirrhosis without transaminitis is much more likely with psoriasis patients. Thus, a dermatologist's experience with using systemic medications to treat psoriasis is paramount in successful treatment of PsA.

What medications can we use to treat PsA?

Because halting the progression of PsA is the key to limiting long-term sequelae, systemic therapy is the mainstay of treatment. Treatment options range from methotrexate to most of the newer biologics. Acitretin tends to be ineffective. Apremilast is approved by the US Food and Drug Administration, and Janus kinase (JAK) inhibitors also have demonstrated efficacy in PsA trials. There are some biologics that are used for PsA but do not have an approval for psoriasis, such as certolizumab pegol.

What's new in PsA?

The literature is well established in the classic progression and presentation of PsA, but there is new evidence that the development of PsA in patients with psoriasis is preceded by a period of nonspecific musculoskeletal symptoms, such as joint pain, arthralgia, fatigue, heel pain, and stiffness (Eder et al). The presence of these symptoms may help guide focused questioning and examination.

Another recent study has shown that the incidence of Crohn disease and ulcerative colitis are more likely in patients with PsA (Zohar et al). It is another important consideration for our patients, especially with recent concerns regarding onset of inflammatory bowel disease with some of the newer biologics we may use to treat psoriasis.

As newer classes of biologic treatments emerge, it will be interesting to see how effective they are in treating PsA in addition to plaque psoriasis. We should be aggressive about treating our patients with psoriasis using systemic therapy if they develop joint pain.

Suggested Readings

Eder L, Polachek A, Rosen CF, et al. The development of PsA in patients with psoriasis is preceded by a period of non-specific musculoskeletal symptoms: a prospective cohort study [published online October 28, 2016]. Arthritis Rheumatol. doi:10.1002/art.39973.

Zohar A, Cohen AD, Bitterman H, et al. Gastrointestinal comorbidities in patients with psoriatic arthritis [published online August 17, 2016]. Clin Rheumatol. 2016;35:2679-2684.

How does psoriatic arthritis present?

Psoriatic arthritis (PsA) can present in psoriasis patients with an average latency of approximately 10 years. In patients with a strong genetic predisposition, another more severe form of PsA can present earlier in life (<20 years of age). Although PsA generally is classified as a seronegative spondyloarthropathy, more than 10% of patients may in fact be rheumatoid factor-positive. Nail pitting is a feature that can suggest the possibility of PsA, present in almost 90% of patients with PsA.

Who should treat PsA?

Although involving our colleagues in rheumatology is usually beneficial for our patients, in most cases dermatologists can and should effectively manage the care of PsA. The immunology of PsA is the same as psoriasis, which contrasts with rheumatoid arthritis (RA). Although active human immunodeficiency virus infection can trigger widespread psoriasis and PsA, RA conversely improves with the depletion of CD4+ cells. Methotrexate, which is used cavalierly by rheumatologists for RA, has a different effect in psoriasis; liver damage is 3 times as likely in psoriasis versus RA at the same doses, while cirrhosis without transaminitis is much more likely with psoriasis patients. Thus, a dermatologist's experience with using systemic medications to treat psoriasis is paramount in successful treatment of PsA.

What medications can we use to treat PsA?

Because halting the progression of PsA is the key to limiting long-term sequelae, systemic therapy is the mainstay of treatment. Treatment options range from methotrexate to most of the newer biologics. Acitretin tends to be ineffective. Apremilast is approved by the US Food and Drug Administration, and Janus kinase (JAK) inhibitors also have demonstrated efficacy in PsA trials. There are some biologics that are used for PsA but do not have an approval for psoriasis, such as certolizumab pegol.

What's new in PsA?

The literature is well established in the classic progression and presentation of PsA, but there is new evidence that the development of PsA in patients with psoriasis is preceded by a period of nonspecific musculoskeletal symptoms, such as joint pain, arthralgia, fatigue, heel pain, and stiffness (Eder et al). The presence of these symptoms may help guide focused questioning and examination.

Another recent study has shown that the incidence of Crohn disease and ulcerative colitis are more likely in patients with PsA (Zohar et al). It is another important consideration for our patients, especially with recent concerns regarding onset of inflammatory bowel disease with some of the newer biologics we may use to treat psoriasis.

As newer classes of biologic treatments emerge, it will be interesting to see how effective they are in treating PsA in addition to plaque psoriasis. We should be aggressive about treating our patients with psoriasis using systemic therapy if they develop joint pain.

Suggested Readings

Eder L, Polachek A, Rosen CF, et al. The development of PsA in patients with psoriasis is preceded by a period of non-specific musculoskeletal symptoms: a prospective cohort study [published online October 28, 2016]. Arthritis Rheumatol. doi:10.1002/art.39973.

Zohar A, Cohen AD, Bitterman H, et al. Gastrointestinal comorbidities in patients with psoriatic arthritis [published online August 17, 2016]. Clin Rheumatol. 2016;35:2679-2684.

How does psoriatic arthritis present?

Psoriatic arthritis (PsA) can present in psoriasis patients with an average latency of approximately 10 years. In patients with a strong genetic predisposition, another more severe form of PsA can present earlier in life (<20 years of age). Although PsA generally is classified as a seronegative spondyloarthropathy, more than 10% of patients may in fact be rheumatoid factor-positive. Nail pitting is a feature that can suggest the possibility of PsA, present in almost 90% of patients with PsA.

Who should treat PsA?

Although involving our colleagues in rheumatology is usually beneficial for our patients, in most cases dermatologists can and should effectively manage the care of PsA. The immunology of PsA is the same as psoriasis, which contrasts with rheumatoid arthritis (RA). Although active human immunodeficiency virus infection can trigger widespread psoriasis and PsA, RA conversely improves with the depletion of CD4+ cells. Methotrexate, which is used cavalierly by rheumatologists for RA, has a different effect in psoriasis; liver damage is 3 times as likely in psoriasis versus RA at the same doses, while cirrhosis without transaminitis is much more likely with psoriasis patients. Thus, a dermatologist's experience with using systemic medications to treat psoriasis is paramount in successful treatment of PsA.

What medications can we use to treat PsA?

Because halting the progression of PsA is the key to limiting long-term sequelae, systemic therapy is the mainstay of treatment. Treatment options range from methotrexate to most of the newer biologics. Acitretin tends to be ineffective. Apremilast is approved by the US Food and Drug Administration, and Janus kinase (JAK) inhibitors also have demonstrated efficacy in PsA trials. There are some biologics that are used for PsA but do not have an approval for psoriasis, such as certolizumab pegol.

What's new in PsA?

The literature is well established in the classic progression and presentation of PsA, but there is new evidence that the development of PsA in patients with psoriasis is preceded by a period of nonspecific musculoskeletal symptoms, such as joint pain, arthralgia, fatigue, heel pain, and stiffness (Eder et al). The presence of these symptoms may help guide focused questioning and examination.

Another recent study has shown that the incidence of Crohn disease and ulcerative colitis are more likely in patients with PsA (Zohar et al). It is another important consideration for our patients, especially with recent concerns regarding onset of inflammatory bowel disease with some of the newer biologics we may use to treat psoriasis.

As newer classes of biologic treatments emerge, it will be interesting to see how effective they are in treating PsA in addition to plaque psoriasis. We should be aggressive about treating our patients with psoriasis using systemic therapy if they develop joint pain.

Suggested Readings

Eder L, Polachek A, Rosen CF, et al. The development of PsA in patients with psoriasis is preceded by a period of non-specific musculoskeletal symptoms: a prospective cohort study [published online October 28, 2016]. Arthritis Rheumatol. doi:10.1002/art.39973.

Zohar A, Cohen AD, Bitterman H, et al. Gastrointestinal comorbidities in patients with psoriatic arthritis [published online August 17, 2016]. Clin Rheumatol. 2016;35:2679-2684.

An experimental biological agent, GP2015, demonstrated equivalent efficacy and comparable safety to etanercept for moderate to severe plaque psoriasis in a manufacturer-sponsored study, according to a report published online in the British Journal of Dermatology.

These findings should contribute to the confirmation of GP2015 as an etanercept (Enbrel) biosimilar for this patient population. Proposed biosimilars such as GP2015 are follow-on versions of authorized biological products, and regulatory authorities require that they demonstrate similarity with a large body of physiochemical and clinical data before they can be confirmed as biosimilars, said Christopher Griffiths, MD, of the Dermatology Centre, Salford Royal Hospital, University of Manchester (England), and his associates.

To contribute such data, Dr. Griffiths and his associates studied the efficacy and safety of GP2015 compared with etanercept, a tumor necrosis factor blocker, in the 2-year EGALITY trial. They assessed 531 adults at 74 medical centers in 11 European countries and South Africa, all of whom had active but stable chronic plaque psoriasis affecting 10% or more of their body surface area and Psoriasis Area and Severity Index (PASI) scores of 10 or more.

The study participants were randomly assigned in approximately equal numbers in a double-blind fashion to self administer GP2015 or etanercept subcutaneously, twice weekly for 12 weeks. Those who achieved at least a 50% improvement in PASI score were then randomized to continue the same treatment once weekly or to undergo a series of three treatment “switches” between GP2015 and etanercept at 6-week intervals until week 30. During an extension phase of the study, participants could then continue to receive the same treatment they had ended on, until week 52.

The primary efficacy endpoint – the percentage of patients who showed at least a 75% improvement from baseline in PASI score (PASI 75) at 12 weeks – was 73.4% with GP2015 and 75.7% with etanercept, which demonstrated therapeutic equivalence. A secondary efficacy end point – mean change in PASI score from baseline to week 12 – also was similar between the two study drugs. In all treatment groups, both PASI mean scores and change in PASI scores over time were comparable between the two study groups, regardless of switching between the two agents. In addition, in all groups, PASI 75 and PASI 90 scores increased gradually over time until week 30, and then remained stable through week 52, the investigators said (Br J Dermatol. 2016. doi: 10.1111/bjd.15152).

The proportion of patients with at least one treatment-emergent adverse event was similar in the GP2015 and etanercept groups who did not switch agents (59.8% and 57.3%, respectively), and was also similar among those who did switch agents between GP2015 (61%) and etanercept (59.4%).

The rates of serious adverse events and of adverse events that led to withdrawal from the study were similar across all treatment groups. Immunogenicity of GP2015 was similar to etanercept.

However, the rate of “adverse events of special interest” – those referred to in special warnings and precautions on the etanercept label – was markedly higher for continued GP2015 than for continued etanercept (11.0% vs. 4.7%) and for switched GP2015 than for switched etanercept (11.0% vs. 5.2%). One patient who took etanercept throughout the trial developed malignant melanoma.

The results of the study “confirm biosimilarity that was established with all previous analytical comparisons to the reference product in that equivalent efficacy was demonstrated as well as similar safety and immunogenicity of GP2015” with etanercept, “in a highly sensitive, generally immune-competent population,” the authors concluded.

The study was funded by Hexal AG, a Sandoz company, which was involved in the study design, data collection and analysis, and manuscript preparation. Dr. Griffiths reported ties to AbbVie, BMS. Galderma, Janssen, Leo-Pharma, Lilly, MSD, Novartis, Pfizer, Regeneron, Roche, Sandoz, and UCB Pharma, and his associates reported ties to numerous industry sources.

An experimental biological agent, GP2015, demonstrated equivalent efficacy and comparable safety to etanercept for moderate to severe plaque psoriasis in a manufacturer-sponsored study, according to a report published online in the British Journal of Dermatology.

These findings should contribute to the confirmation of GP2015 as an etanercept (Enbrel) biosimilar for this patient population. Proposed biosimilars such as GP2015 are follow-on versions of authorized biological products, and regulatory authorities require that they demonstrate similarity with a large body of physiochemical and clinical data before they can be confirmed as biosimilars, said Christopher Griffiths, MD, of the Dermatology Centre, Salford Royal Hospital, University of Manchester (England), and his associates.

To contribute such data, Dr. Griffiths and his associates studied the efficacy and safety of GP2015 compared with etanercept, a tumor necrosis factor blocker, in the 2-year EGALITY trial. They assessed 531 adults at 74 medical centers in 11 European countries and South Africa, all of whom had active but stable chronic plaque psoriasis affecting 10% or more of their body surface area and Psoriasis Area and Severity Index (PASI) scores of 10 or more.

The study participants were randomly assigned in approximately equal numbers in a double-blind fashion to self administer GP2015 or etanercept subcutaneously, twice weekly for 12 weeks. Those who achieved at least a 50% improvement in PASI score were then randomized to continue the same treatment once weekly or to undergo a series of three treatment “switches” between GP2015 and etanercept at 6-week intervals until week 30. During an extension phase of the study, participants could then continue to receive the same treatment they had ended on, until week 52.

The primary efficacy endpoint – the percentage of patients who showed at least a 75% improvement from baseline in PASI score (PASI 75) at 12 weeks – was 73.4% with GP2015 and 75.7% with etanercept, which demonstrated therapeutic equivalence. A secondary efficacy end point – mean change in PASI score from baseline to week 12 – also was similar between the two study drugs. In all treatment groups, both PASI mean scores and change in PASI scores over time were comparable between the two study groups, regardless of switching between the two agents. In addition, in all groups, PASI 75 and PASI 90 scores increased gradually over time until week 30, and then remained stable through week 52, the investigators said (Br J Dermatol. 2016. doi: 10.1111/bjd.15152).

The proportion of patients with at least one treatment-emergent adverse event was similar in the GP2015 and etanercept groups who did not switch agents (59.8% and 57.3%, respectively), and was also similar among those who did switch agents between GP2015 (61%) and etanercept (59.4%).

The rates of serious adverse events and of adverse events that led to withdrawal from the study were similar across all treatment groups. Immunogenicity of GP2015 was similar to etanercept.

However, the rate of “adverse events of special interest” – those referred to in special warnings and precautions on the etanercept label – was markedly higher for continued GP2015 than for continued etanercept (11.0% vs. 4.7%) and for switched GP2015 than for switched etanercept (11.0% vs. 5.2%). One patient who took etanercept throughout the trial developed malignant melanoma.

The results of the study “confirm biosimilarity that was established with all previous analytical comparisons to the reference product in that equivalent efficacy was demonstrated as well as similar safety and immunogenicity of GP2015” with etanercept, “in a highly sensitive, generally immune-competent population,” the authors concluded.

The study was funded by Hexal AG, a Sandoz company, which was involved in the study design, data collection and analysis, and manuscript preparation. Dr. Griffiths reported ties to AbbVie, BMS. Galderma, Janssen, Leo-Pharma, Lilly, MSD, Novartis, Pfizer, Regeneron, Roche, Sandoz, and UCB Pharma, and his associates reported ties to numerous industry sources.

An experimental biological agent, GP2015, demonstrated equivalent efficacy and comparable safety to etanercept for moderate to severe plaque psoriasis in a manufacturer-sponsored study, according to a report published online in the British Journal of Dermatology.

These findings should contribute to the confirmation of GP2015 as an etanercept (Enbrel) biosimilar for this patient population. Proposed biosimilars such as GP2015 are follow-on versions of authorized biological products, and regulatory authorities require that they demonstrate similarity with a large body of physiochemical and clinical data before they can be confirmed as biosimilars, said Christopher Griffiths, MD, of the Dermatology Centre, Salford Royal Hospital, University of Manchester (England), and his associates.

To contribute such data, Dr. Griffiths and his associates studied the efficacy and safety of GP2015 compared with etanercept, a tumor necrosis factor blocker, in the 2-year EGALITY trial. They assessed 531 adults at 74 medical centers in 11 European countries and South Africa, all of whom had active but stable chronic plaque psoriasis affecting 10% or more of their body surface area and Psoriasis Area and Severity Index (PASI) scores of 10 or more.

The study participants were randomly assigned in approximately equal numbers in a double-blind fashion to self administer GP2015 or etanercept subcutaneously, twice weekly for 12 weeks. Those who achieved at least a 50% improvement in PASI score were then randomized to continue the same treatment once weekly or to undergo a series of three treatment “switches” between GP2015 and etanercept at 6-week intervals until week 30. During an extension phase of the study, participants could then continue to receive the same treatment they had ended on, until week 52.

The primary efficacy endpoint – the percentage of patients who showed at least a 75% improvement from baseline in PASI score (PASI 75) at 12 weeks – was 73.4% with GP2015 and 75.7% with etanercept, which demonstrated therapeutic equivalence. A secondary efficacy end point – mean change in PASI score from baseline to week 12 – also was similar between the two study drugs. In all treatment groups, both PASI mean scores and change in PASI scores over time were comparable between the two study groups, regardless of switching between the two agents. In addition, in all groups, PASI 75 and PASI 90 scores increased gradually over time until week 30, and then remained stable through week 52, the investigators said (Br J Dermatol. 2016. doi: 10.1111/bjd.15152).

The proportion of patients with at least one treatment-emergent adverse event was similar in the GP2015 and etanercept groups who did not switch agents (59.8% and 57.3%, respectively), and was also similar among those who did switch agents between GP2015 (61%) and etanercept (59.4%).

The rates of serious adverse events and of adverse events that led to withdrawal from the study were similar across all treatment groups. Immunogenicity of GP2015 was similar to etanercept.

However, the rate of “adverse events of special interest” – those referred to in special warnings and precautions on the etanercept label – was markedly higher for continued GP2015 than for continued etanercept (11.0% vs. 4.7%) and for switched GP2015 than for switched etanercept (11.0% vs. 5.2%). One patient who took etanercept throughout the trial developed malignant melanoma.

The results of the study “confirm biosimilarity that was established with all previous analytical comparisons to the reference product in that equivalent efficacy was demonstrated as well as similar safety and immunogenicity of GP2015” with etanercept, “in a highly sensitive, generally immune-competent population,” the authors concluded.

The study was funded by Hexal AG, a Sandoz company, which was involved in the study design, data collection and analysis, and manuscript preparation. Dr. Griffiths reported ties to AbbVie, BMS. Galderma, Janssen, Leo-Pharma, Lilly, MSD, Novartis, Pfizer, Regeneron, Roche, Sandoz, and UCB Pharma, and his associates reported ties to numerous industry sources.

Dallas dermatologist Alan Menter, MD, doesn’t boast bullying-prevention superpowers, but what he does have is close enough: An eagerness to get the word out to anyone – parent or principal, psychologist or pediatrician – who can help prevent a child with psoriasis from being bullied.

Over his long career, Dr. Menter has made many calls to adults in positions of influence over children. “I’ve talked to pediatricians, and I’ve even called up schools and talked to principals to try get the bullying situation reduced to an extent where the kids can live happy, normal lives without kids taunting them.”

Dr. Menter, chief of dermatology at Baylor University in Dallas, has plenty of company. Other dermatologists are paying close attention to their youngest patients with psoriasis as researchers work to get a better handle on the bullying problem.

dermnews@frontlinemedcom.com

Dallas dermatologist Alan Menter, MD, doesn’t boast bullying-prevention superpowers, but what he does have is close enough: An eagerness to get the word out to anyone – parent or principal, psychologist or pediatrician – who can help prevent a child with psoriasis from being bullied.

Over his long career, Dr. Menter has made many calls to adults in positions of influence over children. “I’ve talked to pediatricians, and I’ve even called up schools and talked to principals to try get the bullying situation reduced to an extent where the kids can live happy, normal lives without kids taunting them.”

Dr. Menter, chief of dermatology at Baylor University in Dallas, has plenty of company. Other dermatologists are paying close attention to their youngest patients with psoriasis as researchers work to get a better handle on the bullying problem.

dermnews@frontlinemedcom.com

Dallas dermatologist Alan Menter, MD, doesn’t boast bullying-prevention superpowers, but what he does have is close enough: An eagerness to get the word out to anyone – parent or principal, psychologist or pediatrician – who can help prevent a child with psoriasis from being bullied.

Over his long career, Dr. Menter has made many calls to adults in positions of influence over children. “I’ve talked to pediatricians, and I’ve even called up schools and talked to principals to try get the bullying situation reduced to an extent where the kids can live happy, normal lives without kids taunting them.”

Dr. Menter, chief of dermatology at Baylor University in Dallas, has plenty of company. Other dermatologists are paying close attention to their youngest patients with psoriasis as researchers work to get a better handle on the bullying problem.

dermnews@frontlinemedcom.com

LAS VEGAS – Physicians often fail to predict the impact of disease on quality of life in their psoriasis patients, which can help guide treatment, Joel Gelfand, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas dermatology seminar.

“This is true across all medical conditions,” said Dr. Gelfand, professor of dermatology, at the University of Pennsylvania, Philadelphia. For example, some patients with psoriasis may have extensive disease, but it doesn’t bother them, and therefore they may need less treatment, he pointed out.

In his practice, patients with psoriasis are asked to rate physical symptoms (including flaking and itching) and emotional symptoms (including anxiety and depression) related to their disease on a scale of 0 to 10, with 10 being the worst. “The higher those scores are, the more aggressive I’ll be in treating them,” he said. Patient scores can be tracked over time, to review progress with their chosen treatment, he noted.

Dr. Gelfand disclosed relationships with multiple companies including AbbVie, Janssen, Lilly, Novartis, Celgene, Merck, Sanofi, Pfizer, and Valeant.

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

LAS VEGAS – Physicians often fail to predict the impact of disease on quality of life in their psoriasis patients, which can help guide treatment, Joel Gelfand, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas dermatology seminar.

“This is true across all medical conditions,” said Dr. Gelfand, professor of dermatology, at the University of Pennsylvania, Philadelphia. For example, some patients with psoriasis may have extensive disease, but it doesn’t bother them, and therefore they may need less treatment, he pointed out.

In his practice, patients with psoriasis are asked to rate physical symptoms (including flaking and itching) and emotional symptoms (including anxiety and depression) related to their disease on a scale of 0 to 10, with 10 being the worst. “The higher those scores are, the more aggressive I’ll be in treating them,” he said. Patient scores can be tracked over time, to review progress with their chosen treatment, he noted.

Dr. Gelfand disclosed relationships with multiple companies including AbbVie, Janssen, Lilly, Novartis, Celgene, Merck, Sanofi, Pfizer, and Valeant.

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

LAS VEGAS – Physicians often fail to predict the impact of disease on quality of life in their psoriasis patients, which can help guide treatment, Joel Gelfand, MD, said in a video interview at Skin Disease Education Foundation’s annual Las Vegas dermatology seminar.

“This is true across all medical conditions,” said Dr. Gelfand, professor of dermatology, at the University of Pennsylvania, Philadelphia. For example, some patients with psoriasis may have extensive disease, but it doesn’t bother them, and therefore they may need less treatment, he pointed out.

In his practice, patients with psoriasis are asked to rate physical symptoms (including flaking and itching) and emotional symptoms (including anxiety and depression) related to their disease on a scale of 0 to 10, with 10 being the worst. “The higher those scores are, the more aggressive I’ll be in treating them,” he said. Patient scores can be tracked over time, to review progress with their chosen treatment, he noted.

Dr. Gelfand disclosed relationships with multiple companies including AbbVie, Janssen, Lilly, Novartis, Celgene, Merck, Sanofi, Pfizer, and Valeant.

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

CenterWatch (http://www.centerwatch.com/) is an online resource that provides directories, analysis, and market research of medications that are either under clinical evaluation or available for use in patients. A list of currently approved drugs by the US Food and Drug Administration (FDA) also is available by specialty. It is important for dermatologists in-training to know about recently approved drugs and those that are in the pipeline, as these treatments may benefit patients who are unresponsive to other previously used medications. New drugs also may be useful for physicians who have a difficult time getting insurance to cover prescriptions for their patients, as most new medications have built-in patient assistance.

New Drugs in Dermatology

Actinic Keratosis

Ameluz (aminolevulinic acid hydrochloride)(Biofrontera AG) is a new drug that was approved in May 2016 for treatment of mild to moderate actinic keratosis on the face and scalp.¹ It is only intended for in-office use on patients who may not be candidates for other treatment options for actinic keratosis. The product is a gel formulation that should be applied to cover the lesions and approximately 5 mm of the surrounding area with a film of approximately 1-mm thickness. The entire treatment area is then illuminated with a red light source, either with a narrow spectrum around 630 nm with a light dose of approximately 37 J/cm² or a broader and continuous spectrum in the range of 570 to 670 nm with a light dose between 75 and 200 J/cm².¹ Similar to the previously used aminolevulinic acid treatment method for actinic keratosis, the patient may experience a burning stinging sensation throughout the treatment and the skin will then proceed to peel.

Psoriasis and Psoriatic Arthritis

Taltz (ixekizumab)(Eli Lilly and Company) was approved by the FDA in March 2016 for the treatment of moderate to severe plaque psoriasis.² It is a humanized IL-17A antagonist that works when IgG4 monoclonal antibodies selectively bind with IL-17A cytokines and inhibit their interaction with the IL-17 receptor. Although this injectable medication is approved for the treatment of psoriasis, it also can potentially be used off label for the treatment of psoriatic arthritis and rheumatoid arthritis. The approved dosage is 160 mg (two 80-mg injections) at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.² Injectable immunomodulatory medications such as ixekizumab are ideal for patients in whom topical treatments and light therapy failed and they continue to have serious psoriatic discomfort as well as for those who have substantial body surface area coverage.

Melanoma

Cotellic (cobimetinib)(Genentech USA, Inc) was FDA approved in November 2015.⁴ Cobimetinib is a reversible inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase 1. Mitogen-activated protein kinase MEK1 and MEK2 are regulators of the extracellular signal-­related kinase pathway, which promotes cellular proliferation. This pathway is key, as melanomas that have a BRAF V600E and kinase mutation continue to proliferate due to the constitutive activation of MEK1 and MEK2, further promoting cellular proliferation. Cobimetinib is approved for the treatment of melanoma in patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in conjunction with vemurafenib. Zelboraf (vemurafenib)(Genentech USA, Inc), another inhibitor of BRAF V600E, also is used for the treatment of unresectable melanomas and was initially approved in 2011.⁵

BRAF is a serine/threonine protein kinase. When unregulated, it results in the deregulation of cell proliferation. According to Ascierto et al,⁶ 50% of melanomas have a BRAF mutation, with nearly 90% of them with a V600E mutation. Hence, since the advent of direct chemotherapeutic agents such as BRAF inhibitors, clinical trials have shown notable reduction in mortality and morbidity of melanoma patients with BRAF mutations.⁶

Imlygic (talimogene laherparepvec)(Amgen, Inc) is a modified oncolytic viral therapy.⁷ This treatment was approved by the FDA in 2015 and replicates within tumors to produce granulocyte-macrophage colony-stimulating factor protein, which promotes an antitumor immune response within unresectable cutaneous, subcutaneous, and nodal melanoma lesions. Although it is not a gene-directed therapy, the melanoma does not require a specific mutation for treatment. Again, this medication is better served in conjunction with other melanoma chemotherapeutic and surgical interventions.

Submental Fat

Kybella (deoxycholic acid)(Allergan) is a nonhuman, nonanimal, synthetically created compound that is naturally found within the human body for the breakdown and absorption of dietary fat.⁸ This drug was FDA approved in 2015 for the improvement of the appearance of moderate subcutaneous fat under the chin. Patients are evaluated in clinic to determine if the submental fat would be responsive to an injectable or require more radical surgical intervention based on desired outcomes. The treatment is administered as 0.2-mL injections (up to a total of 10 mL) spaced 1-cm apart and ideally is repeated at regular intervals to evaluate for efficacy.

Basal Cell Carcinoma

Odomzo (sonidegib)(Novartis Corporation) was FDA approved in 2015 for locally advanced basal cell carcinoma.⁹ Odomzo is a smoothened antagonist that inhibits the hedgehog signaling pathway. Smoothened is a transmembrane protein that allows for signal transduction of hedgehog proteins.¹⁰ Protein patched homolog 1 binds to smoothened protein and prevents the signal transduction through the cell for Gli family zinc factor 1 to continue protein translation; however, when PTCH is mutated and can no longer bind to smoothened, tumor formation results, specifically basal cell carcinoma. Hence, sonidegib is for the treatment of basal cell carcinomas that have persisted despite radiation treatment and/or surgery as well as for patients who have multiple basal cell carcinomas that can no longer be treated with surgery or radiation.

Final Thoughts

Overall, although there are several medications that can be used in conjunction for treatment of dermatological conditions, it always is recommended to know what is in the pipeline as FDA-approved medications for dermatology.

CenterWatch (http://www.centerwatch.com/) is an online resource that provides directories, analysis, and market research of medications that are either under clinical evaluation or available for use in patients. A list of currently approved drugs by the US Food and Drug Administration (FDA) also is available by specialty. It is important for dermatologists in-training to know about recently approved drugs and those that are in the pipeline, as these treatments may benefit patients who are unresponsive to other previously used medications. New drugs also may be useful for physicians who have a difficult time getting insurance to cover prescriptions for their patients, as most new medications have built-in patient assistance.

New Drugs in Dermatology

Actinic Keratosis

Ameluz (aminolevulinic acid hydrochloride)(Biofrontera AG) is a new drug that was approved in May 2016 for treatment of mild to moderate actinic keratosis on the face and scalp.¹ It is only intended for in-office use on patients who may not be candidates for other treatment options for actinic keratosis. The product is a gel formulation that should be applied to cover the lesions and approximately 5 mm of the surrounding area with a film of approximately 1-mm thickness. The entire treatment area is then illuminated with a red light source, either with a narrow spectrum around 630 nm with a light dose of approximately 37 J/cm² or a broader and continuous spectrum in the range of 570 to 670 nm with a light dose between 75 and 200 J/cm².¹ Similar to the previously used aminolevulinic acid treatment method for actinic keratosis, the patient may experience a burning stinging sensation throughout the treatment and the skin will then proceed to peel.

Psoriasis and Psoriatic Arthritis

Taltz (ixekizumab)(Eli Lilly and Company) was approved by the FDA in March 2016 for the treatment of moderate to severe plaque psoriasis.² It is a humanized IL-17A antagonist that works when IgG4 monoclonal antibodies selectively bind with IL-17A cytokines and inhibit their interaction with the IL-17 receptor. Although this injectable medication is approved for the treatment of psoriasis, it also can potentially be used off label for the treatment of psoriatic arthritis and rheumatoid arthritis. The approved dosage is 160 mg (two 80-mg injections) at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.² Injectable immunomodulatory medications such as ixekizumab are ideal for patients in whom topical treatments and light therapy failed and they continue to have serious psoriatic discomfort as well as for those who have substantial body surface area coverage.

Melanoma

Cotellic (cobimetinib)(Genentech USA, Inc) was FDA approved in November 2015.⁴ Cobimetinib is a reversible inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase 1. Mitogen-activated protein kinase MEK1 and MEK2 are regulators of the extracellular signal-­related kinase pathway, which promotes cellular proliferation. This pathway is key, as melanomas that have a BRAF V600E and kinase mutation continue to proliferate due to the constitutive activation of MEK1 and MEK2, further promoting cellular proliferation. Cobimetinib is approved for the treatment of melanoma in patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in conjunction with vemurafenib. Zelboraf (vemurafenib)(Genentech USA, Inc), another inhibitor of BRAF V600E, also is used for the treatment of unresectable melanomas and was initially approved in 2011.⁵

BRAF is a serine/threonine protein kinase. When unregulated, it results in the deregulation of cell proliferation. According to Ascierto et al,⁶ 50% of melanomas have a BRAF mutation, with nearly 90% of them with a V600E mutation. Hence, since the advent of direct chemotherapeutic agents such as BRAF inhibitors, clinical trials have shown notable reduction in mortality and morbidity of melanoma patients with BRAF mutations.⁶

Imlygic (talimogene laherparepvec)(Amgen, Inc) is a modified oncolytic viral therapy.⁷ This treatment was approved by the FDA in 2015 and replicates within tumors to produce granulocyte-macrophage colony-stimulating factor protein, which promotes an antitumor immune response within unresectable cutaneous, subcutaneous, and nodal melanoma lesions. Although it is not a gene-directed therapy, the melanoma does not require a specific mutation for treatment. Again, this medication is better served in conjunction with other melanoma chemotherapeutic and surgical interventions.

Submental Fat

Kybella (deoxycholic acid)(Allergan) is a nonhuman, nonanimal, synthetically created compound that is naturally found within the human body for the breakdown and absorption of dietary fat.⁸ This drug was FDA approved in 2015 for the improvement of the appearance of moderate subcutaneous fat under the chin. Patients are evaluated in clinic to determine if the submental fat would be responsive to an injectable or require more radical surgical intervention based on desired outcomes. The treatment is administered as 0.2-mL injections (up to a total of 10 mL) spaced 1-cm apart and ideally is repeated at regular intervals to evaluate for efficacy.

Basal Cell Carcinoma

Odomzo (sonidegib)(Novartis Corporation) was FDA approved in 2015 for locally advanced basal cell carcinoma.⁹ Odomzo is a smoothened antagonist that inhibits the hedgehog signaling pathway. Smoothened is a transmembrane protein that allows for signal transduction of hedgehog proteins.¹⁰ Protein patched homolog 1 binds to smoothened protein and prevents the signal transduction through the cell for Gli family zinc factor 1 to continue protein translation; however, when PTCH is mutated and can no longer bind to smoothened, tumor formation results, specifically basal cell carcinoma. Hence, sonidegib is for the treatment of basal cell carcinomas that have persisted despite radiation treatment and/or surgery as well as for patients who have multiple basal cell carcinomas that can no longer be treated with surgery or radiation.

Final Thoughts

Overall, although there are several medications that can be used in conjunction for treatment of dermatological conditions, it always is recommended to know what is in the pipeline as FDA-approved medications for dermatology.

CenterWatch (http://www.centerwatch.com/) is an online resource that provides directories, analysis, and market research of medications that are either under clinical evaluation or available for use in patients. A list of currently approved drugs by the US Food and Drug Administration (FDA) also is available by specialty. It is important for dermatologists in-training to know about recently approved drugs and those that are in the pipeline, as these treatments may benefit patients who are unresponsive to other previously used medications. New drugs also may be useful for physicians who have a difficult time getting insurance to cover prescriptions for their patients, as most new medications have built-in patient assistance.

New Drugs in Dermatology

Actinic Keratosis

Ameluz (aminolevulinic acid hydrochloride)(Biofrontera AG) is a new drug that was approved in May 2016 for treatment of mild to moderate actinic keratosis on the face and scalp.¹ It is only intended for in-office use on patients who may not be candidates for other treatment options for actinic keratosis. The product is a gel formulation that should be applied to cover the lesions and approximately 5 mm of the surrounding area with a film of approximately 1-mm thickness. The entire treatment area is then illuminated with a red light source, either with a narrow spectrum around 630 nm with a light dose of approximately 37 J/cm² or a broader and continuous spectrum in the range of 570 to 670 nm with a light dose between 75 and 200 J/cm².¹ Similar to the previously used aminolevulinic acid treatment method for actinic keratosis, the patient may experience a burning stinging sensation throughout the treatment and the skin will then proceed to peel.

Psoriasis and Psoriatic Arthritis

Taltz (ixekizumab)(Eli Lilly and Company) was approved by the FDA in March 2016 for the treatment of moderate to severe plaque psoriasis.² It is a humanized IL-17A antagonist that works when IgG4 monoclonal antibodies selectively bind with IL-17A cytokines and inhibit their interaction with the IL-17 receptor. Although this injectable medication is approved for the treatment of psoriasis, it also can potentially be used off label for the treatment of psoriatic arthritis and rheumatoid arthritis. The approved dosage is 160 mg (two 80-mg injections) at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.² Injectable immunomodulatory medications such as ixekizumab are ideal for patients in whom topical treatments and light therapy failed and they continue to have serious psoriatic discomfort as well as for those who have substantial body surface area coverage.

Melanoma

Cotellic (cobimetinib)(Genentech USA, Inc) was FDA approved in November 2015.⁴ Cobimetinib is a reversible inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase 1. Mitogen-activated protein kinase MEK1 and MEK2 are regulators of the extracellular signal-­related kinase pathway, which promotes cellular proliferation. This pathway is key, as melanomas that have a BRAF V600E and kinase mutation continue to proliferate due to the constitutive activation of MEK1 and MEK2, further promoting cellular proliferation. Cobimetinib is approved for the treatment of melanoma in patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in conjunction with vemurafenib. Zelboraf (vemurafenib)(Genentech USA, Inc), another inhibitor of BRAF V600E, also is used for the treatment of unresectable melanomas and was initially approved in 2011.⁵

BRAF is a serine/threonine protein kinase. When unregulated, it results in the deregulation of cell proliferation. According to Ascierto et al,⁶ 50% of melanomas have a BRAF mutation, with nearly 90% of them with a V600E mutation. Hence, since the advent of direct chemotherapeutic agents such as BRAF inhibitors, clinical trials have shown notable reduction in mortality and morbidity of melanoma patients with BRAF mutations.⁶

Imlygic (talimogene laherparepvec)(Amgen, Inc) is a modified oncolytic viral therapy.⁷ This treatment was approved by the FDA in 2015 and replicates within tumors to produce granulocyte-macrophage colony-stimulating factor protein, which promotes an antitumor immune response within unresectable cutaneous, subcutaneous, and nodal melanoma lesions. Although it is not a gene-directed therapy, the melanoma does not require a specific mutation for treatment. Again, this medication is better served in conjunction with other melanoma chemotherapeutic and surgical interventions.

Submental Fat

Kybella (deoxycholic acid)(Allergan) is a nonhuman, nonanimal, synthetically created compound that is naturally found within the human body for the breakdown and absorption of dietary fat.⁸ This drug was FDA approved in 2015 for the improvement of the appearance of moderate subcutaneous fat under the chin. Patients are evaluated in clinic to determine if the submental fat would be responsive to an injectable or require more radical surgical intervention based on desired outcomes. The treatment is administered as 0.2-mL injections (up to a total of 10 mL) spaced 1-cm apart and ideally is repeated at regular intervals to evaluate for efficacy.

Basal Cell Carcinoma

Odomzo (sonidegib)(Novartis Corporation) was FDA approved in 2015 for locally advanced basal cell carcinoma.⁹ Odomzo is a smoothened antagonist that inhibits the hedgehog signaling pathway. Smoothened is a transmembrane protein that allows for signal transduction of hedgehog proteins.¹⁰ Protein patched homolog 1 binds to smoothened protein and prevents the signal transduction through the cell for Gli family zinc factor 1 to continue protein translation; however, when PTCH is mutated and can no longer bind to smoothened, tumor formation results, specifically basal cell carcinoma. Hence, sonidegib is for the treatment of basal cell carcinomas that have persisted despite radiation treatment and/or surgery as well as for patients who have multiple basal cell carcinomas that can no longer be treated with surgery or radiation.

Final Thoughts

Overall, although there are several medications that can be used in conjunction for treatment of dermatological conditions, it always is recommended to know what is in the pipeline as FDA-approved medications for dermatology.

VIENNA – Psoriasis in children and adolescents is associated with significantly increased risk of a variety of psychiatric comorbidities, according to a large Danish national study.

This finding has important public health implications. Psoriasis is a common skin disease, and 30% of cases have their onset in childhood or adolescence, Tanja Todberg, MD, observed at the annual congress of the European Academy of Dermatology and Venereology.

VIENNA – Psoriasis in children and adolescents is associated with significantly increased risk of a variety of psychiatric comorbidities, according to a large Danish national study.

This finding has important public health implications. Psoriasis is a common skin disease, and 30% of cases have their onset in childhood or adolescence, Tanja Todberg, MD, observed at the annual congress of the European Academy of Dermatology and Venereology.

VIENNA – Psoriasis in children and adolescents is associated with significantly increased risk of a variety of psychiatric comorbidities, according to a large Danish national study.

This finding has important public health implications. Psoriasis is a common skin disease, and 30% of cases have their onset in childhood or adolescence, Tanja Todberg, MD, observed at the annual congress of the European Academy of Dermatology and Venereology.