Psoriasis

According to the US Food and Drug Administration (FDA), a biosimilar is “highly similar to an FDA-approved biological product, . . . and has no clinically meaningful differences in terms of safety and effectiveness.”¹ The Biologics Price Competition and Innovation (BPCI) Act of 2009 created an expedited pathway for the approval of products shown to be biosimilar to FDA-licensed reference products.² In 2013, the European Medicines Agency approved the first biosimilar modeled on infliximab (Remsima [formerly known as CT-P13], Celltrion Healthcare Co, Ltd) for the same indications as its reference product.³ In 2016, the FDA approved Inflectra (Hospira, a Pfizer Company), an infliximab biosimilar; Erelzi (Sandoz, a Novartis Division), an etanercept biosimilar; and Amjevita (Amgen Inc), an adalimumab biosimilar, all for numerous clinical indications including plaque psoriasis and psoriatic arthritis.^4-6

There has been a substantial amount of distrust surrounding the biosimilars; however, as the patents for the biologic agents expire, new biosimilars will undoubtedly flood the market. In this article, we provide information that will help dermatologists understand the need for and use of these agents.

Biosimilars Versus Generic Drugs

Small-molecule generics can be made in a process that is relatively inexpensive, reproducible, and able to yield identical products with each lot.⁷ In contrast, biosimilars are large complex proteins made in living cells. They differ from their reference product because of changes that occur during manufacturing (eg, purification system, posttranslational modifications).^7-9 Glycosylation is particularly sensitive to manufacturing and can affect the immunogenicity of the product.⁹ The impact of manufacturing can be substantial; for example, during phase 3 trials for efalizumab, a change in the manufacturing facility affected pharmacokinetic properties to such a degree that the FDA required a repeat of the trials.¹⁰

FDA Guidelines on Biosimilarity

The FDA outlines the following approach to demonstrate biosimilarity.² The first step is structural characterization to evaluate the primary, secondary, tertiary, and quaternary structures and posttranslational modifications. The next step utilizes in vivo and/or in vitro functional assays to compare the biosimilar and reference product. The third step is a focus on toxicity and immunogenicity. The fourth step involves clinical studies to study pharmacokinetic and pharmacodynamic data, immunogenicity, safety, and efficacy. After the biosimilar has been approved, there must be a system in place to monitor postmarketing safety. If a biosimilar is tested in one patient population (eg, patients with plaque psoriasis), a request can be made to approve the drug for all the conditions that the reference product was approved for, such as plaque psoriasis, rheumatoid arthritis, and inflammatory bowel disease, even though clinical trials were not performed in all of these patient populations.² The BPCI Act leaves it up to the FDA to determine how much and what type of data (eg, in vitro, in vivo, clinical) are required.¹¹

Extrapolation and Interchangeability

Once a biosimilar has been approved, 2 questions must be answered: First, can its use be extrapolated to all indications for the reference product? The infliximab biosimilar approved by the European Medicines Agency and the FDA had only been studied in patients with ankylosing spondylitis¹² and rheumatoid arthritis,¹³ yet it was granted all the indications for infliximab, including severe plaque psoriasis.¹⁴ As of now, the various regulatory agencies differ on their policies regarding extrapolation. Extrapolation is not automatically bestowed on a biosimilar in the United States but can be requested by the manufacturer.²

Second, can the biosimilar be seamlessly switched with its reference product at the pharmacy level? The BPCI Act allows for the substitution of biosimilars that are deemed interchangeable without notifying the provider, yet individual states ultimately can pass laws regarding this issue.^15,16 An interchangeable agent would “produce the same clinical result as the reference product,” and “the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is not greater than the risk of using the reference product.”¹⁵ Generic drugs are allowed to be substituted without notifying the patient or prescriber¹⁶; however, biosimilars that are not deemed interchangeable would require permission from the prescriber before substitution.¹¹

Biosimilars for Psoriasis

In April 2016, an infliximab biosimilar (Inflectra) became the second biosimilar approved by the FDA.⁴ Inflectra was studied in clinical trials for patients with ankylosing spondylitis¹⁷ and rheumatoid arthritis,¹⁸ and in both trials the biosimilar was found to have similar efficacy and safety profiles to that of the reference product. In August 2016, an etanercept biosimilar (Erelzi) was approved,⁵ and in September 2016, an adalimumab biosimilar (Amjevita) was approved.⁶

The Table summarizes clinical trials (both completed and ongoing) evaluating biosimilars in adults with plaque psoriasis; thus far, there are 2464 participants enrolled across 5 different studies of adalimumab biosimilars (registered at www.clinicaltrials.gov with the identifiers NCT01970488, NCT02016105, NCT02489227, NCT02714322, NCT02581345) and 531 participants in an etanercept biosimilar study (NCT01891864).

A phase 3 double-blind study compared adalimumab to an adalimumab biosimilar (ABP 501) in 350 adults with plaque psoriasis (NCT01970488). Participants received an initial loading dose of adalimumab (n=175) or ABP 501 (n=175) 80 mg subcutaneously on week 1/day 1, followed by 40 mg at week 2 every 2 weeks thereafter. At week 16, participants with psoriasis area and severity index (PASI) 50 or greater remained in the study for up to 52 weeks; those who were receiving adalimumab were re-randomized to receive either ABP 501 or adalimumab. Participants receiving ABP 501 continued to receive the biosimilar. The mean PASI improvement at weeks 16, 32, and 50 was 86.6, 87.6, and 87.2, respectively, in the ABP 501/ABP 501 group (A/A) compared to 88.0, 88.2, and 88.1, respectively, in the adalimumab/adalimumab group (B/B).¹⁹ Autoantibodies developed in 68.4% of participants in the A/A group compared to 74.7% in the B/B group. The incidence of treatment-emergent adverse events (TEAEs) was 86.2% in the A/A group and 78.5% in the B/B group. The most common TEAEs were nasopharyngitis, headache, and upper respiratory tract infection. The incidence of serious TEAEs was 4.6% in the A/A group compared to 5.1% in the B/B group. Overall, the efficacy, safety, and immunogenicity of the adalimumab biosimilar was comparable to the reference product.¹⁹

A second phase 3 trial (ADACCESS) evaluated the adalimumab biosimilar GP2017 (NCT02016105). Participants received an initial dose of 80 mg subcutaneously of either GP2017 or adalimumab at week 0, followed by 40 mg every other week starting at week 1 and ending at week 51. The study has been completed but results are not yet available.

The third trial is evaluating the adalimumab biosimilar CHS-1420 (NCT02489227). Participants in the experimental arm receive two 40-mg doses of CHS-1420 at week 0/day 0, and then 1 dose every 2 weeks from week 1 for 23 weeks. At week 24, participants continue with an open-label study. Participants in the adalimumab group receive two 40-mg doses at week 0/day 0, and then 1 dose every 2 weeks from week 1 to week 15. At week 16, participants will be re-randomized (1:1) to continue adalimumab or start CHS-1420 at one 40-mg dose every 2 weeks during weeks 17 to 23. At week 24, participants will switch to CHS-1420 open label until the end of the study. Study results are not yet available; the study is ongoing but not recruiting.

The fourth ongoing trial is evaluating the adalimumab biosimilar MYL-1401A (NCT02714322). Participants receive an initial dose of 80 mg subcutaneously of either MYL-1401A or adalimumab (2:1), followed by 40 mg every other week starting 1 week after the initial dose. After the 52-week treatment period, there is an 8-week safety follow-up period. Study results are not yet available; the study is ongoing but not recruiting.

A fifth adalimumab biosimilar, M923, also is currently being tested in clinical trials (NCT02581345). Participants receive either M923, adalimumab, or alternate between the 2 agents. Although the study is still ongoing, data released from the manufacturer state that the proportion of participants who achieved PASI 75 after 16 weeks of treatment was equivalent in the 2 treatment groups. The proportion of participants who achieved PASI 90, as well as the type, frequency, and severity of adverse events, also were comparable.²⁰

The EGALITY trial, completed in March 2015, compared the etanercept biosimilar GP2015 to etanercept over a 52-week period (NCT01891864). Participants received either GP2015 or etanercept 50 mg twice weekly for the first 12 weeks. Participants with at least PASI 50 were then re-randomized into 4 groups: the first 2 groups stayed with their current treatments while the other 2 groups alternated treatments every 6 weeks until week 30. Participants then stayed on their last treatment from week 30 to week 52. The adjusted PASI 75 response rate at week 12 was 73.4% in the group receiving GP2015 and 75.7% in the group receiving etanercept.²¹ The percentage change in PASI score at all time points was found to be comparable from baseline until week 52. Importantly, the incidence of TEAEs up to week 52 was comparable and no new safety issues were reported. Additionally, switching participants from etanercept to the biosimilar during the subsequent treatment periods did not cause an increase in formation of antidrug antibodies.²¹

There are 2 upcoming studies involving biosimilars that are not yet recruiting patients. The first (NCT02925338) will analyze the characteristics of patients treated with Inflectra as well as their response to treatment. The second (NCT02762955) will be comparing the efficacy and safety of an adalimumab biosimilar (BCD-057, BIOCAD) to adalimumab.

Economic Advantages of Biosimilars

The annual economic burden of psoriasis in the United States is substantial, with estimates between $35.2 billion²² and $112 billion.²³ Biosimilars can be 25% to 30% cheaper than their reference products^9,11,24 and have the potential to save the US health care system billions of dollars.²⁵ Furthermore, the developers of biosimilars could offer patient assistance programs.¹¹ That being said, drug developers can extend patents for their branded drugs; for instance, 2 patents for Enbrel (Amgen Inc) could protect the drug until 2029.^26,27

Although cost is an important factor in deciding which medications to prescribe for patients, it should never take precedence over safety and efficacy. Manufacturers can develop new drugs with greater efficacy, fewer side effects, or more convenient dosing schedules,^26,27 or they could offer co-payment assistance programs.^26,28 Physicians also must consider how the biosimilars will be integrated into drug formularies. Would patients be required to use a biosimilar before a branded drug?^11,29 Will patients already taking a branded drug be grandfathered in?¹¹ Would they have to pay a premium to continue taking their drug? And finally, could changes in formularies and employer-payer relationships destabilize patient regimens?³⁰

Conclusion

Preliminary results suggest that biosimilars can have similar safety, efficacy, and immunogenicity data compared to their reference products.^19,21 Biosimilars have the potential to greatly reduce the cost burden associated with psoriasis. However, how similar is “highly similar”? Although cost is an important consideration in selecting drug therapies, the reason for using a biosimilar should never be based on cost alone.

According to the US Food and Drug Administration (FDA), a biosimilar is “highly similar to an FDA-approved biological product, . . . and has no clinically meaningful differences in terms of safety and effectiveness.”¹ The Biologics Price Competition and Innovation (BPCI) Act of 2009 created an expedited pathway for the approval of products shown to be biosimilar to FDA-licensed reference products.² In 2013, the European Medicines Agency approved the first biosimilar modeled on infliximab (Remsima [formerly known as CT-P13], Celltrion Healthcare Co, Ltd) for the same indications as its reference product.³ In 2016, the FDA approved Inflectra (Hospira, a Pfizer Company), an infliximab biosimilar; Erelzi (Sandoz, a Novartis Division), an etanercept biosimilar; and Amjevita (Amgen Inc), an adalimumab biosimilar, all for numerous clinical indications including plaque psoriasis and psoriatic arthritis.^4-6

There has been a substantial amount of distrust surrounding the biosimilars; however, as the patents for the biologic agents expire, new biosimilars will undoubtedly flood the market. In this article, we provide information that will help dermatologists understand the need for and use of these agents.

Biosimilars Versus Generic Drugs

Small-molecule generics can be made in a process that is relatively inexpensive, reproducible, and able to yield identical products with each lot.⁷ In contrast, biosimilars are large complex proteins made in living cells. They differ from their reference product because of changes that occur during manufacturing (eg, purification system, posttranslational modifications).^7-9 Glycosylation is particularly sensitive to manufacturing and can affect the immunogenicity of the product.⁹ The impact of manufacturing can be substantial; for example, during phase 3 trials for efalizumab, a change in the manufacturing facility affected pharmacokinetic properties to such a degree that the FDA required a repeat of the trials.¹⁰

FDA Guidelines on Biosimilarity

The FDA outlines the following approach to demonstrate biosimilarity.² The first step is structural characterization to evaluate the primary, secondary, tertiary, and quaternary structures and posttranslational modifications. The next step utilizes in vivo and/or in vitro functional assays to compare the biosimilar and reference product. The third step is a focus on toxicity and immunogenicity. The fourth step involves clinical studies to study pharmacokinetic and pharmacodynamic data, immunogenicity, safety, and efficacy. After the biosimilar has been approved, there must be a system in place to monitor postmarketing safety. If a biosimilar is tested in one patient population (eg, patients with plaque psoriasis), a request can be made to approve the drug for all the conditions that the reference product was approved for, such as plaque psoriasis, rheumatoid arthritis, and inflammatory bowel disease, even though clinical trials were not performed in all of these patient populations.² The BPCI Act leaves it up to the FDA to determine how much and what type of data (eg, in vitro, in vivo, clinical) are required.¹¹

Extrapolation and Interchangeability

Once a biosimilar has been approved, 2 questions must be answered: First, can its use be extrapolated to all indications for the reference product? The infliximab biosimilar approved by the European Medicines Agency and the FDA had only been studied in patients with ankylosing spondylitis¹² and rheumatoid arthritis,¹³ yet it was granted all the indications for infliximab, including severe plaque psoriasis.¹⁴ As of now, the various regulatory agencies differ on their policies regarding extrapolation. Extrapolation is not automatically bestowed on a biosimilar in the United States but can be requested by the manufacturer.²

Second, can the biosimilar be seamlessly switched with its reference product at the pharmacy level? The BPCI Act allows for the substitution of biosimilars that are deemed interchangeable without notifying the provider, yet individual states ultimately can pass laws regarding this issue.^15,16 An interchangeable agent would “produce the same clinical result as the reference product,” and “the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is not greater than the risk of using the reference product.”¹⁵ Generic drugs are allowed to be substituted without notifying the patient or prescriber¹⁶; however, biosimilars that are not deemed interchangeable would require permission from the prescriber before substitution.¹¹

Biosimilars for Psoriasis

In April 2016, an infliximab biosimilar (Inflectra) became the second biosimilar approved by the FDA.⁴ Inflectra was studied in clinical trials for patients with ankylosing spondylitis¹⁷ and rheumatoid arthritis,¹⁸ and in both trials the biosimilar was found to have similar efficacy and safety profiles to that of the reference product. In August 2016, an etanercept biosimilar (Erelzi) was approved,⁵ and in September 2016, an adalimumab biosimilar (Amjevita) was approved.⁶

The Table summarizes clinical trials (both completed and ongoing) evaluating biosimilars in adults with plaque psoriasis; thus far, there are 2464 participants enrolled across 5 different studies of adalimumab biosimilars (registered at www.clinicaltrials.gov with the identifiers NCT01970488, NCT02016105, NCT02489227, NCT02714322, NCT02581345) and 531 participants in an etanercept biosimilar study (NCT01891864).

A phase 3 double-blind study compared adalimumab to an adalimumab biosimilar (ABP 501) in 350 adults with plaque psoriasis (NCT01970488). Participants received an initial loading dose of adalimumab (n=175) or ABP 501 (n=175) 80 mg subcutaneously on week 1/day 1, followed by 40 mg at week 2 every 2 weeks thereafter. At week 16, participants with psoriasis area and severity index (PASI) 50 or greater remained in the study for up to 52 weeks; those who were receiving adalimumab were re-randomized to receive either ABP 501 or adalimumab. Participants receiving ABP 501 continued to receive the biosimilar. The mean PASI improvement at weeks 16, 32, and 50 was 86.6, 87.6, and 87.2, respectively, in the ABP 501/ABP 501 group (A/A) compared to 88.0, 88.2, and 88.1, respectively, in the adalimumab/adalimumab group (B/B).¹⁹ Autoantibodies developed in 68.4% of participants in the A/A group compared to 74.7% in the B/B group. The incidence of treatment-emergent adverse events (TEAEs) was 86.2% in the A/A group and 78.5% in the B/B group. The most common TEAEs were nasopharyngitis, headache, and upper respiratory tract infection. The incidence of serious TEAEs was 4.6% in the A/A group compared to 5.1% in the B/B group. Overall, the efficacy, safety, and immunogenicity of the adalimumab biosimilar was comparable to the reference product.¹⁹

A second phase 3 trial (ADACCESS) evaluated the adalimumab biosimilar GP2017 (NCT02016105). Participants received an initial dose of 80 mg subcutaneously of either GP2017 or adalimumab at week 0, followed by 40 mg every other week starting at week 1 and ending at week 51. The study has been completed but results are not yet available.

The third trial is evaluating the adalimumab biosimilar CHS-1420 (NCT02489227). Participants in the experimental arm receive two 40-mg doses of CHS-1420 at week 0/day 0, and then 1 dose every 2 weeks from week 1 for 23 weeks. At week 24, participants continue with an open-label study. Participants in the adalimumab group receive two 40-mg doses at week 0/day 0, and then 1 dose every 2 weeks from week 1 to week 15. At week 16, participants will be re-randomized (1:1) to continue adalimumab or start CHS-1420 at one 40-mg dose every 2 weeks during weeks 17 to 23. At week 24, participants will switch to CHS-1420 open label until the end of the study. Study results are not yet available; the study is ongoing but not recruiting.

The fourth ongoing trial is evaluating the adalimumab biosimilar MYL-1401A (NCT02714322). Participants receive an initial dose of 80 mg subcutaneously of either MYL-1401A or adalimumab (2:1), followed by 40 mg every other week starting 1 week after the initial dose. After the 52-week treatment period, there is an 8-week safety follow-up period. Study results are not yet available; the study is ongoing but not recruiting.

A fifth adalimumab biosimilar, M923, also is currently being tested in clinical trials (NCT02581345). Participants receive either M923, adalimumab, or alternate between the 2 agents. Although the study is still ongoing, data released from the manufacturer state that the proportion of participants who achieved PASI 75 after 16 weeks of treatment was equivalent in the 2 treatment groups. The proportion of participants who achieved PASI 90, as well as the type, frequency, and severity of adverse events, also were comparable.²⁰

The EGALITY trial, completed in March 2015, compared the etanercept biosimilar GP2015 to etanercept over a 52-week period (NCT01891864). Participants received either GP2015 or etanercept 50 mg twice weekly for the first 12 weeks. Participants with at least PASI 50 were then re-randomized into 4 groups: the first 2 groups stayed with their current treatments while the other 2 groups alternated treatments every 6 weeks until week 30. Participants then stayed on their last treatment from week 30 to week 52. The adjusted PASI 75 response rate at week 12 was 73.4% in the group receiving GP2015 and 75.7% in the group receiving etanercept.²¹ The percentage change in PASI score at all time points was found to be comparable from baseline until week 52. Importantly, the incidence of TEAEs up to week 52 was comparable and no new safety issues were reported. Additionally, switching participants from etanercept to the biosimilar during the subsequent treatment periods did not cause an increase in formation of antidrug antibodies.²¹

There are 2 upcoming studies involving biosimilars that are not yet recruiting patients. The first (NCT02925338) will analyze the characteristics of patients treated with Inflectra as well as their response to treatment. The second (NCT02762955) will be comparing the efficacy and safety of an adalimumab biosimilar (BCD-057, BIOCAD) to adalimumab.

Economic Advantages of Biosimilars

The annual economic burden of psoriasis in the United States is substantial, with estimates between $35.2 billion²² and $112 billion.²³ Biosimilars can be 25% to 30% cheaper than their reference products^9,11,24 and have the potential to save the US health care system billions of dollars.²⁵ Furthermore, the developers of biosimilars could offer patient assistance programs.¹¹ That being said, drug developers can extend patents for their branded drugs; for instance, 2 patents for Enbrel (Amgen Inc) could protect the drug until 2029.^26,27

Although cost is an important factor in deciding which medications to prescribe for patients, it should never take precedence over safety and efficacy. Manufacturers can develop new drugs with greater efficacy, fewer side effects, or more convenient dosing schedules,^26,27 or they could offer co-payment assistance programs.^26,28 Physicians also must consider how the biosimilars will be integrated into drug formularies. Would patients be required to use a biosimilar before a branded drug?^11,29 Will patients already taking a branded drug be grandfathered in?¹¹ Would they have to pay a premium to continue taking their drug? And finally, could changes in formularies and employer-payer relationships destabilize patient regimens?³⁰

Conclusion

Preliminary results suggest that biosimilars can have similar safety, efficacy, and immunogenicity data compared to their reference products.^19,21 Biosimilars have the potential to greatly reduce the cost burden associated with psoriasis. However, how similar is “highly similar”? Although cost is an important consideration in selecting drug therapies, the reason for using a biosimilar should never be based on cost alone.

According to the US Food and Drug Administration (FDA), a biosimilar is “highly similar to an FDA-approved biological product, . . . and has no clinically meaningful differences in terms of safety and effectiveness.”¹ The Biologics Price Competition and Innovation (BPCI) Act of 2009 created an expedited pathway for the approval of products shown to be biosimilar to FDA-licensed reference products.² In 2013, the European Medicines Agency approved the first biosimilar modeled on infliximab (Remsima [formerly known as CT-P13], Celltrion Healthcare Co, Ltd) for the same indications as its reference product.³ In 2016, the FDA approved Inflectra (Hospira, a Pfizer Company), an infliximab biosimilar; Erelzi (Sandoz, a Novartis Division), an etanercept biosimilar; and Amjevita (Amgen Inc), an adalimumab biosimilar, all for numerous clinical indications including plaque psoriasis and psoriatic arthritis.^4-6

There has been a substantial amount of distrust surrounding the biosimilars; however, as the patents for the biologic agents expire, new biosimilars will undoubtedly flood the market. In this article, we provide information that will help dermatologists understand the need for and use of these agents.

Biosimilars Versus Generic Drugs

Small-molecule generics can be made in a process that is relatively inexpensive, reproducible, and able to yield identical products with each lot.⁷ In contrast, biosimilars are large complex proteins made in living cells. They differ from their reference product because of changes that occur during manufacturing (eg, purification system, posttranslational modifications).^7-9 Glycosylation is particularly sensitive to manufacturing and can affect the immunogenicity of the product.⁹ The impact of manufacturing can be substantial; for example, during phase 3 trials for efalizumab, a change in the manufacturing facility affected pharmacokinetic properties to such a degree that the FDA required a repeat of the trials.¹⁰

FDA Guidelines on Biosimilarity

The FDA outlines the following approach to demonstrate biosimilarity.² The first step is structural characterization to evaluate the primary, secondary, tertiary, and quaternary structures and posttranslational modifications. The next step utilizes in vivo and/or in vitro functional assays to compare the biosimilar and reference product. The third step is a focus on toxicity and immunogenicity. The fourth step involves clinical studies to study pharmacokinetic and pharmacodynamic data, immunogenicity, safety, and efficacy. After the biosimilar has been approved, there must be a system in place to monitor postmarketing safety. If a biosimilar is tested in one patient population (eg, patients with plaque psoriasis), a request can be made to approve the drug for all the conditions that the reference product was approved for, such as plaque psoriasis, rheumatoid arthritis, and inflammatory bowel disease, even though clinical trials were not performed in all of these patient populations.² The BPCI Act leaves it up to the FDA to determine how much and what type of data (eg, in vitro, in vivo, clinical) are required.¹¹

Extrapolation and Interchangeability

Once a biosimilar has been approved, 2 questions must be answered: First, can its use be extrapolated to all indications for the reference product? The infliximab biosimilar approved by the European Medicines Agency and the FDA had only been studied in patients with ankylosing spondylitis¹² and rheumatoid arthritis,¹³ yet it was granted all the indications for infliximab, including severe plaque psoriasis.¹⁴ As of now, the various regulatory agencies differ on their policies regarding extrapolation. Extrapolation is not automatically bestowed on a biosimilar in the United States but can be requested by the manufacturer.²

Second, can the biosimilar be seamlessly switched with its reference product at the pharmacy level? The BPCI Act allows for the substitution of biosimilars that are deemed interchangeable without notifying the provider, yet individual states ultimately can pass laws regarding this issue.^15,16 An interchangeable agent would “produce the same clinical result as the reference product,” and “the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is not greater than the risk of using the reference product.”¹⁵ Generic drugs are allowed to be substituted without notifying the patient or prescriber¹⁶; however, biosimilars that are not deemed interchangeable would require permission from the prescriber before substitution.¹¹

Biosimilars for Psoriasis

In April 2016, an infliximab biosimilar (Inflectra) became the second biosimilar approved by the FDA.⁴ Inflectra was studied in clinical trials for patients with ankylosing spondylitis¹⁷ and rheumatoid arthritis,¹⁸ and in both trials the biosimilar was found to have similar efficacy and safety profiles to that of the reference product. In August 2016, an etanercept biosimilar (Erelzi) was approved,⁵ and in September 2016, an adalimumab biosimilar (Amjevita) was approved.⁶

The Table summarizes clinical trials (both completed and ongoing) evaluating biosimilars in adults with plaque psoriasis; thus far, there are 2464 participants enrolled across 5 different studies of adalimumab biosimilars (registered at www.clinicaltrials.gov with the identifiers NCT01970488, NCT02016105, NCT02489227, NCT02714322, NCT02581345) and 531 participants in an etanercept biosimilar study (NCT01891864).

A phase 3 double-blind study compared adalimumab to an adalimumab biosimilar (ABP 501) in 350 adults with plaque psoriasis (NCT01970488). Participants received an initial loading dose of adalimumab (n=175) or ABP 501 (n=175) 80 mg subcutaneously on week 1/day 1, followed by 40 mg at week 2 every 2 weeks thereafter. At week 16, participants with psoriasis area and severity index (PASI) 50 or greater remained in the study for up to 52 weeks; those who were receiving adalimumab were re-randomized to receive either ABP 501 or adalimumab. Participants receiving ABP 501 continued to receive the biosimilar. The mean PASI improvement at weeks 16, 32, and 50 was 86.6, 87.6, and 87.2, respectively, in the ABP 501/ABP 501 group (A/A) compared to 88.0, 88.2, and 88.1, respectively, in the adalimumab/adalimumab group (B/B).¹⁹ Autoantibodies developed in 68.4% of participants in the A/A group compared to 74.7% in the B/B group. The incidence of treatment-emergent adverse events (TEAEs) was 86.2% in the A/A group and 78.5% in the B/B group. The most common TEAEs were nasopharyngitis, headache, and upper respiratory tract infection. The incidence of serious TEAEs was 4.6% in the A/A group compared to 5.1% in the B/B group. Overall, the efficacy, safety, and immunogenicity of the adalimumab biosimilar was comparable to the reference product.¹⁹

A second phase 3 trial (ADACCESS) evaluated the adalimumab biosimilar GP2017 (NCT02016105). Participants received an initial dose of 80 mg subcutaneously of either GP2017 or adalimumab at week 0, followed by 40 mg every other week starting at week 1 and ending at week 51. The study has been completed but results are not yet available.

The third trial is evaluating the adalimumab biosimilar CHS-1420 (NCT02489227). Participants in the experimental arm receive two 40-mg doses of CHS-1420 at week 0/day 0, and then 1 dose every 2 weeks from week 1 for 23 weeks. At week 24, participants continue with an open-label study. Participants in the adalimumab group receive two 40-mg doses at week 0/day 0, and then 1 dose every 2 weeks from week 1 to week 15. At week 16, participants will be re-randomized (1:1) to continue adalimumab or start CHS-1420 at one 40-mg dose every 2 weeks during weeks 17 to 23. At week 24, participants will switch to CHS-1420 open label until the end of the study. Study results are not yet available; the study is ongoing but not recruiting.

The fourth ongoing trial is evaluating the adalimumab biosimilar MYL-1401A (NCT02714322). Participants receive an initial dose of 80 mg subcutaneously of either MYL-1401A or adalimumab (2:1), followed by 40 mg every other week starting 1 week after the initial dose. After the 52-week treatment period, there is an 8-week safety follow-up period. Study results are not yet available; the study is ongoing but not recruiting.

A fifth adalimumab biosimilar, M923, also is currently being tested in clinical trials (NCT02581345). Participants receive either M923, adalimumab, or alternate between the 2 agents. Although the study is still ongoing, data released from the manufacturer state that the proportion of participants who achieved PASI 75 after 16 weeks of treatment was equivalent in the 2 treatment groups. The proportion of participants who achieved PASI 90, as well as the type, frequency, and severity of adverse events, also were comparable.²⁰

The EGALITY trial, completed in March 2015, compared the etanercept biosimilar GP2015 to etanercept over a 52-week period (NCT01891864). Participants received either GP2015 or etanercept 50 mg twice weekly for the first 12 weeks. Participants with at least PASI 50 were then re-randomized into 4 groups: the first 2 groups stayed with their current treatments while the other 2 groups alternated treatments every 6 weeks until week 30. Participants then stayed on their last treatment from week 30 to week 52. The adjusted PASI 75 response rate at week 12 was 73.4% in the group receiving GP2015 and 75.7% in the group receiving etanercept.²¹ The percentage change in PASI score at all time points was found to be comparable from baseline until week 52. Importantly, the incidence of TEAEs up to week 52 was comparable and no new safety issues were reported. Additionally, switching participants from etanercept to the biosimilar during the subsequent treatment periods did not cause an increase in formation of antidrug antibodies.²¹

There are 2 upcoming studies involving biosimilars that are not yet recruiting patients. The first (NCT02925338) will analyze the characteristics of patients treated with Inflectra as well as their response to treatment. The second (NCT02762955) will be comparing the efficacy and safety of an adalimumab biosimilar (BCD-057, BIOCAD) to adalimumab.

Economic Advantages of Biosimilars

The annual economic burden of psoriasis in the United States is substantial, with estimates between $35.2 billion²² and $112 billion.²³ Biosimilars can be 25% to 30% cheaper than their reference products^9,11,24 and have the potential to save the US health care system billions of dollars.²⁵ Furthermore, the developers of biosimilars could offer patient assistance programs.¹¹ That being said, drug developers can extend patents for their branded drugs; for instance, 2 patents for Enbrel (Amgen Inc) could protect the drug until 2029.^26,27

Although cost is an important factor in deciding which medications to prescribe for patients, it should never take precedence over safety and efficacy. Manufacturers can develop new drugs with greater efficacy, fewer side effects, or more convenient dosing schedules,^26,27 or they could offer co-payment assistance programs.^26,28 Physicians also must consider how the biosimilars will be integrated into drug formularies. Would patients be required to use a biosimilar before a branded drug?^11,29 Will patients already taking a branded drug be grandfathered in?¹¹ Would they have to pay a premium to continue taking their drug? And finally, could changes in formularies and employer-payer relationships destabilize patient regimens?³⁰

Conclusion

Preliminary results suggest that biosimilars can have similar safety, efficacy, and immunogenicity data compared to their reference products.^19,21 Biosimilars have the potential to greatly reduce the cost burden associated with psoriasis. However, how similar is “highly similar”? Although cost is an important consideration in selecting drug therapies, the reason for using a biosimilar should never be based on cost alone.

WAILEA, HAWAII – A few attendees at the Hawaii Dermatology Seminar discussed some of the highlights of the presentations during a coffee break at the meeting.

New treatment protocols for psoriasis, details about skin disease in children, managing medication side effects, and promising data about biologics are discussed in this video, as are updates on the latest tips for treating atopic dermatitis.

The interviewees had no conflicts to disclose.

The meeting is provided by Global Academy for Medical Education/Skin Disease Education Foundation. SDEF and this news organization are owned by the same parent company.

WAILEA, HAWAII – A few attendees at the Hawaii Dermatology Seminar discussed some of the highlights of the presentations during a coffee break at the meeting.

New treatment protocols for psoriasis, details about skin disease in children, managing medication side effects, and promising data about biologics are discussed in this video, as are updates on the latest tips for treating atopic dermatitis.

The interviewees had no conflicts to disclose.

The meeting is provided by Global Academy for Medical Education/Skin Disease Education Foundation. SDEF and this news organization are owned by the same parent company.

WAILEA, HAWAII – A few attendees at the Hawaii Dermatology Seminar discussed some of the highlights of the presentations during a coffee break at the meeting.

New treatment protocols for psoriasis, details about skin disease in children, managing medication side effects, and promising data about biologics are discussed in this video, as are updates on the latest tips for treating atopic dermatitis.

The interviewees had no conflicts to disclose.

The meeting is provided by Global Academy for Medical Education/Skin Disease Education Foundation. SDEF and this news organization are owned by the same parent company.

WAILEA, HAWAII – Plaque type psoriasis continues to be the most common type of psoriasis in children, but there are other presentations that should be considered, said Wynnis Tom, MD, a pediatric dermatologist at the University of California, San Diego, and Rady Children’s Hospital, San Diego.

“We certainly see a form of what some people would call napkin dermatitis,” or “diaper psoriasis,” affecting the diaper area in young infants, Dr. Tom said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

So when a child has a more refractory diaper rash, “look around to see if there are other lesions in the surrounding area that might be more typical for psoriasis,” she noted.

“We also see a lot more guttate disease” in children with psoriasis, which is more likely to be related to infections and triggers, Dr. Tom said. The face and scalp are often affected in children, and it is important to attend to these areas early to help avoid social stigma, she added.

Dr. Tom disclosed financial relationships with companies including Celgene, Janssen, and Promius. SDEF and this news organization are owned by the same parent company.

WAILEA, HAWAII – Plaque type psoriasis continues to be the most common type of psoriasis in children, but there are other presentations that should be considered, said Wynnis Tom, MD, a pediatric dermatologist at the University of California, San Diego, and Rady Children’s Hospital, San Diego.

“We certainly see a form of what some people would call napkin dermatitis,” or “diaper psoriasis,” affecting the diaper area in young infants, Dr. Tom said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

So when a child has a more refractory diaper rash, “look around to see if there are other lesions in the surrounding area that might be more typical for psoriasis,” she noted.

“We also see a lot more guttate disease” in children with psoriasis, which is more likely to be related to infections and triggers, Dr. Tom said. The face and scalp are often affected in children, and it is important to attend to these areas early to help avoid social stigma, she added.

Dr. Tom disclosed financial relationships with companies including Celgene, Janssen, and Promius. SDEF and this news organization are owned by the same parent company.

WAILEA, HAWAII – Plaque type psoriasis continues to be the most common type of psoriasis in children, but there are other presentations that should be considered, said Wynnis Tom, MD, a pediatric dermatologist at the University of California, San Diego, and Rady Children’s Hospital, San Diego.

“We certainly see a form of what some people would call napkin dermatitis,” or “diaper psoriasis,” affecting the diaper area in young infants, Dr. Tom said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

So when a child has a more refractory diaper rash, “look around to see if there are other lesions in the surrounding area that might be more typical for psoriasis,” she noted.

“We also see a lot more guttate disease” in children with psoriasis, which is more likely to be related to infections and triggers, Dr. Tom said. The face and scalp are often affected in children, and it is important to attend to these areas early to help avoid social stigma, she added.

Dr. Tom disclosed financial relationships with companies including Celgene, Janssen, and Promius. SDEF and this news organization are owned by the same parent company.

Practice Gap

Early diagnosis of nail psoriasis is challenging because nail changes, including pitting, subungual hyperkeratosis, crumbling, oil spots, salmon patches, onycholysis, and splinter hemorrhages, may be subtle and nonspecific. Furthermore, 5% to 10% of psoriasis patients do not have skin findings, making the diagnosis of nail psoriasis even more difficult. Psoriatic arthritis (PsA) is more common in patients with nail psoriasis than in those with cutaneous psoriasis, and early joint damage may be asymptomatic.¹ Both nail psoriasis and PsA may progress rapidly, leading to functional impairment with poor quality of life.²

Diagnostic Tool

A 36-year-old man presented with a 4-year history of abnormal fingernails. He denied nail pain but stated that the nails felt sensitive at times and it was difficult to pick up small objects. His medical history was notable for type 2 diabetes mellitus, hypertension, and attention deficit disorder. He denied joint pain or skin rash.

Physical examination revealed pitting and onycholysis of the fingernails (Figure, A) without involvement of the toenails. A nail clipping was negative for fungus but revealed an incompletely keratinized nail plate with subungual parakeratotic scale, consistent with nail psoriasis. A radiograph showed erosive changes of the third finger of the right hand that were compatible with PsA (Figure, B).

Practice Implications

A nail clipping may be performed to diagnose nail psoriasis. Imaging and/or referral to a rheumatologist should be performed in all patients with isolated nail psoriasis to evaluate for early arthritic changes. If present, appropriate therapy is initiated to prevent further joint damage. In patients with nail psoriasis with or without associated joint pain, dermatologists should consider using radiograph imaging to screen patients for PsA.

Practice Gap

Early diagnosis of nail psoriasis is challenging because nail changes, including pitting, subungual hyperkeratosis, crumbling, oil spots, salmon patches, onycholysis, and splinter hemorrhages, may be subtle and nonspecific. Furthermore, 5% to 10% of psoriasis patients do not have skin findings, making the diagnosis of nail psoriasis even more difficult. Psoriatic arthritis (PsA) is more common in patients with nail psoriasis than in those with cutaneous psoriasis, and early joint damage may be asymptomatic.¹ Both nail psoriasis and PsA may progress rapidly, leading to functional impairment with poor quality of life.²

Diagnostic Tool

A 36-year-old man presented with a 4-year history of abnormal fingernails. He denied nail pain but stated that the nails felt sensitive at times and it was difficult to pick up small objects. His medical history was notable for type 2 diabetes mellitus, hypertension, and attention deficit disorder. He denied joint pain or skin rash.

Physical examination revealed pitting and onycholysis of the fingernails (Figure, A) without involvement of the toenails. A nail clipping was negative for fungus but revealed an incompletely keratinized nail plate with subungual parakeratotic scale, consistent with nail psoriasis. A radiograph showed erosive changes of the third finger of the right hand that were compatible with PsA (Figure, B).

Practice Implications

A nail clipping may be performed to diagnose nail psoriasis. Imaging and/or referral to a rheumatologist should be performed in all patients with isolated nail psoriasis to evaluate for early arthritic changes. If present, appropriate therapy is initiated to prevent further joint damage. In patients with nail psoriasis with or without associated joint pain, dermatologists should consider using radiograph imaging to screen patients for PsA.

Practice Gap

Early diagnosis of nail psoriasis is challenging because nail changes, including pitting, subungual hyperkeratosis, crumbling, oil spots, salmon patches, onycholysis, and splinter hemorrhages, may be subtle and nonspecific. Furthermore, 5% to 10% of psoriasis patients do not have skin findings, making the diagnosis of nail psoriasis even more difficult. Psoriatic arthritis (PsA) is more common in patients with nail psoriasis than in those with cutaneous psoriasis, and early joint damage may be asymptomatic.¹ Both nail psoriasis and PsA may progress rapidly, leading to functional impairment with poor quality of life.²

Diagnostic Tool

A 36-year-old man presented with a 4-year history of abnormal fingernails. He denied nail pain but stated that the nails felt sensitive at times and it was difficult to pick up small objects. His medical history was notable for type 2 diabetes mellitus, hypertension, and attention deficit disorder. He denied joint pain or skin rash.

Physical examination revealed pitting and onycholysis of the fingernails (Figure, A) without involvement of the toenails. A nail clipping was negative for fungus but revealed an incompletely keratinized nail plate with subungual parakeratotic scale, consistent with nail psoriasis. A radiograph showed erosive changes of the third finger of the right hand that were compatible with PsA (Figure, B).

Practice Implications

A nail clipping may be performed to diagnose nail psoriasis. Imaging and/or referral to a rheumatologist should be performed in all patients with isolated nail psoriasis to evaluate for early arthritic changes. If present, appropriate therapy is initiated to prevent further joint damage. In patients with nail psoriasis with or without associated joint pain, dermatologists should consider using radiograph imaging to screen patients for PsA.

Growing incentives to control health care costs may cause accountable care organizations (ACOs) to reconsider how diseases are best managed. Few studies have examined the cost difference between primary care providers (PCPs) and specialists in managing the same disease. Limited data have suggested that management of some diseases by a PCP may be less costly compared to a specialist^1,2; however, it is not clear if this finding extends to skin disease. This study sought to assess the cost of seeing a dermatologist versus a PCP for diagnosis of the common skin diseases psoriasis and rosacea.

Methods

Patient data were obtained from the Humana database, a large commercial data set for claims and reimbursed costs encompassing 18,162,539 patients covered between January 2007 and December 2014. Our study population consisted of 3,944,465 patients with claims that included International Classification of Diseases, Ninth Revision (ICD-9), codes for dermatological diagnoses (680.0–709.9). We searched by ICD-9 code for US patients with primary diagnoses of psoriasis (696.1) and rosacea (695.3). We narrowed the search to include patients aged 30 to 64 years, as the diagnoses for these diseases are most common in patients older than 30 years. Patients who were older than 64 years were not included in the study, as most are covered by Medicare and therefore costs covered by Humana in this age group would not be as representative as in younger age groups. Total and average diagnosis-related costs per patient were compared between dermatologists and PCPs. Diagnosis-related costs encompassed physician reimbursement; laboratory and imaging costs, including skin biopsies; inpatient hospitalization cost; and any other charge that could be coded or billed by providers and reimbursed by the insurance company. To be eligible for reimbursement from Humana, dermatologists and PCPs must be registered with the insurer according to specialty board certification and practice credentialing, and they are reimbursed differently based on specialty. Drug costs, which would possibly skew the data toward providers using more expensive systemic medications (ie, dermatologists), were not included in this study, as the discussion is better reserved for long-term management of disease rather than diagnosis-related costs. All diagnoses of psoriasis were included in the study, which likely includes all severities of psoriasis, though we did not have the ability to further break down these diagnoses by severity.

Results

We identified 30,217 psoriasis patients and 37,561 rosacea patients. Of those patients with a primary diagnosis of psoriasis, 26,112 (86%) were seen by a dermatologist and 4105 (14%) were seen by a PCP (Table). Of those patients with a primary diagnosis of rosacea, 34,694 (92%) were seen by a dermatologist and 2867 (8%) were seen by a PCP (Table). There was little difference in the average diagnosis-related cost per patient for psoriasis in males (dermatologists, $638; PCPs, $657) versus females (dermatologists, $592; PCPs, $586) or between specialties (Figure). Findings were similar for rosacea in males (dermatologists, $179; PCPs, $168) versus females (dermatologists, $157; PCPs, $161). For these skin diseases, it was concluded that it is not more cost-effective to be diagnosed by a PCP versus a dermatologist.

Comment

For the management of common skin disorders such as psoriasis and rosacea, there is little cost difference in seeing a dermatologist versus a PCP. Through extensive training and repeated exposure to many skin diseases, dermatologists are expected to be more comfortable in diagnosing and managing psoriasis and rosacea. Compared to PCPs, dermatologists have demonstrated increased diagnostic accuracy and efficiency when examining pigmented lesions and other dermatologic diseases in several studies.^3-6 Although the current study shows that diagnosis-related costs for psoriasis and rosacea are essentially equal between dermatologists and PCPs, it actually may be less expensive for patients to see a dermatologist, as unnecessary tests, biopsies, or medications are more likely to be ordered/prescribed when there is less clinical diagnostic certainty.^7,8 Additionally, seeing a PCP for diagnosis of a skin disease may be inefficient if subsequent referral to a dermatologist is needed, a common scenario that occurs when patients see a PCP for skin conditions.⁹

Our study had limitations, which is typical of a study using a claims database. We used ICD-9 codes recorded in patients’ medical claims to determine diagnosis of psoriasis and rosacea; therefore, our study and data are subject to coding errors. We could not assess the severity of disease, only the presence of disease. Further confirmation of diagnosis could have been made through searching for a second ICD-9 code in the patient’s history. Our data also are from a limited time period and may not represent costs from other time periods.

Conclusion

Given the lack of cost difference between both specialties, we conclude that ACOs should consider encouraging patients to seek care for dermatologic diseases by dermatologists who generally are more accurate and efficient skin diagnosticians, particularly if there is a shortage of PCPs within the ACO network.

Growing incentives to control health care costs may cause accountable care organizations (ACOs) to reconsider how diseases are best managed. Few studies have examined the cost difference between primary care providers (PCPs) and specialists in managing the same disease. Limited data have suggested that management of some diseases by a PCP may be less costly compared to a specialist^1,2; however, it is not clear if this finding extends to skin disease. This study sought to assess the cost of seeing a dermatologist versus a PCP for diagnosis of the common skin diseases psoriasis and rosacea.

Methods

Patient data were obtained from the Humana database, a large commercial data set for claims and reimbursed costs encompassing 18,162,539 patients covered between January 2007 and December 2014. Our study population consisted of 3,944,465 patients with claims that included International Classification of Diseases, Ninth Revision (ICD-9), codes for dermatological diagnoses (680.0–709.9). We searched by ICD-9 code for US patients with primary diagnoses of psoriasis (696.1) and rosacea (695.3). We narrowed the search to include patients aged 30 to 64 years, as the diagnoses for these diseases are most common in patients older than 30 years. Patients who were older than 64 years were not included in the study, as most are covered by Medicare and therefore costs covered by Humana in this age group would not be as representative as in younger age groups. Total and average diagnosis-related costs per patient were compared between dermatologists and PCPs. Diagnosis-related costs encompassed physician reimbursement; laboratory and imaging costs, including skin biopsies; inpatient hospitalization cost; and any other charge that could be coded or billed by providers and reimbursed by the insurance company. To be eligible for reimbursement from Humana, dermatologists and PCPs must be registered with the insurer according to specialty board certification and practice credentialing, and they are reimbursed differently based on specialty. Drug costs, which would possibly skew the data toward providers using more expensive systemic medications (ie, dermatologists), were not included in this study, as the discussion is better reserved for long-term management of disease rather than diagnosis-related costs. All diagnoses of psoriasis were included in the study, which likely includes all severities of psoriasis, though we did not have the ability to further break down these diagnoses by severity.

Results

We identified 30,217 psoriasis patients and 37,561 rosacea patients. Of those patients with a primary diagnosis of psoriasis, 26,112 (86%) were seen by a dermatologist and 4105 (14%) were seen by a PCP (Table). Of those patients with a primary diagnosis of rosacea, 34,694 (92%) were seen by a dermatologist and 2867 (8%) were seen by a PCP (Table). There was little difference in the average diagnosis-related cost per patient for psoriasis in males (dermatologists, $638; PCPs, $657) versus females (dermatologists, $592; PCPs, $586) or between specialties (Figure). Findings were similar for rosacea in males (dermatologists, $179; PCPs, $168) versus females (dermatologists, $157; PCPs, $161). For these skin diseases, it was concluded that it is not more cost-effective to be diagnosed by a PCP versus a dermatologist.

Comment

For the management of common skin disorders such as psoriasis and rosacea, there is little cost difference in seeing a dermatologist versus a PCP. Through extensive training and repeated exposure to many skin diseases, dermatologists are expected to be more comfortable in diagnosing and managing psoriasis and rosacea. Compared to PCPs, dermatologists have demonstrated increased diagnostic accuracy and efficiency when examining pigmented lesions and other dermatologic diseases in several studies.^3-6 Although the current study shows that diagnosis-related costs for psoriasis and rosacea are essentially equal between dermatologists and PCPs, it actually may be less expensive for patients to see a dermatologist, as unnecessary tests, biopsies, or medications are more likely to be ordered/prescribed when there is less clinical diagnostic certainty.^7,8 Additionally, seeing a PCP for diagnosis of a skin disease may be inefficient if subsequent referral to a dermatologist is needed, a common scenario that occurs when patients see a PCP for skin conditions.⁹

Our study had limitations, which is typical of a study using a claims database. We used ICD-9 codes recorded in patients’ medical claims to determine diagnosis of psoriasis and rosacea; therefore, our study and data are subject to coding errors. We could not assess the severity of disease, only the presence of disease. Further confirmation of diagnosis could have been made through searching for a second ICD-9 code in the patient’s history. Our data also are from a limited time period and may not represent costs from other time periods.

Conclusion

Given the lack of cost difference between both specialties, we conclude that ACOs should consider encouraging patients to seek care for dermatologic diseases by dermatologists who generally are more accurate and efficient skin diagnosticians, particularly if there is a shortage of PCPs within the ACO network.

Growing incentives to control health care costs may cause accountable care organizations (ACOs) to reconsider how diseases are best managed. Few studies have examined the cost difference between primary care providers (PCPs) and specialists in managing the same disease. Limited data have suggested that management of some diseases by a PCP may be less costly compared to a specialist^1,2; however, it is not clear if this finding extends to skin disease. This study sought to assess the cost of seeing a dermatologist versus a PCP for diagnosis of the common skin diseases psoriasis and rosacea.

Methods

Patient data were obtained from the Humana database, a large commercial data set for claims and reimbursed costs encompassing 18,162,539 patients covered between January 2007 and December 2014. Our study population consisted of 3,944,465 patients with claims that included International Classification of Diseases, Ninth Revision (ICD-9), codes for dermatological diagnoses (680.0–709.9). We searched by ICD-9 code for US patients with primary diagnoses of psoriasis (696.1) and rosacea (695.3). We narrowed the search to include patients aged 30 to 64 years, as the diagnoses for these diseases are most common in patients older than 30 years. Patients who were older than 64 years were not included in the study, as most are covered by Medicare and therefore costs covered by Humana in this age group would not be as representative as in younger age groups. Total and average diagnosis-related costs per patient were compared between dermatologists and PCPs. Diagnosis-related costs encompassed physician reimbursement; laboratory and imaging costs, including skin biopsies; inpatient hospitalization cost; and any other charge that could be coded or billed by providers and reimbursed by the insurance company. To be eligible for reimbursement from Humana, dermatologists and PCPs must be registered with the insurer according to specialty board certification and practice credentialing, and they are reimbursed differently based on specialty. Drug costs, which would possibly skew the data toward providers using more expensive systemic medications (ie, dermatologists), were not included in this study, as the discussion is better reserved for long-term management of disease rather than diagnosis-related costs. All diagnoses of psoriasis were included in the study, which likely includes all severities of psoriasis, though we did not have the ability to further break down these diagnoses by severity.

Results

We identified 30,217 psoriasis patients and 37,561 rosacea patients. Of those patients with a primary diagnosis of psoriasis, 26,112 (86%) were seen by a dermatologist and 4105 (14%) were seen by a PCP (Table). Of those patients with a primary diagnosis of rosacea, 34,694 (92%) were seen by a dermatologist and 2867 (8%) were seen by a PCP (Table). There was little difference in the average diagnosis-related cost per patient for psoriasis in males (dermatologists, $638; PCPs, $657) versus females (dermatologists, $592; PCPs, $586) or between specialties (Figure). Findings were similar for rosacea in males (dermatologists, $179; PCPs, $168) versus females (dermatologists, $157; PCPs, $161). For these skin diseases, it was concluded that it is not more cost-effective to be diagnosed by a PCP versus a dermatologist.

Comment

For the management of common skin disorders such as psoriasis and rosacea, there is little cost difference in seeing a dermatologist versus a PCP. Through extensive training and repeated exposure to many skin diseases, dermatologists are expected to be more comfortable in diagnosing and managing psoriasis and rosacea. Compared to PCPs, dermatologists have demonstrated increased diagnostic accuracy and efficiency when examining pigmented lesions and other dermatologic diseases in several studies.^3-6 Although the current study shows that diagnosis-related costs for psoriasis and rosacea are essentially equal between dermatologists and PCPs, it actually may be less expensive for patients to see a dermatologist, as unnecessary tests, biopsies, or medications are more likely to be ordered/prescribed when there is less clinical diagnostic certainty.^7,8 Additionally, seeing a PCP for diagnosis of a skin disease may be inefficient if subsequent referral to a dermatologist is needed, a common scenario that occurs when patients see a PCP for skin conditions.⁹

Our study had limitations, which is typical of a study using a claims database. We used ICD-9 codes recorded in patients’ medical claims to determine diagnosis of psoriasis and rosacea; therefore, our study and data are subject to coding errors. We could not assess the severity of disease, only the presence of disease. Further confirmation of diagnosis could have been made through searching for a second ICD-9 code in the patient’s history. Our data also are from a limited time period and may not represent costs from other time periods.

Conclusion

Given the lack of cost difference between both specialties, we conclude that ACOs should consider encouraging patients to seek care for dermatologic diseases by dermatologists who generally are more accurate and efficient skin diagnosticians, particularly if there is a shortage of PCPs within the ACO network.

The role of current biologic therapies in psoriasis predicates on the pathogenic role of upregulated, immune-related mechanisms that result in the activation of myeloid dendritic cells, which release IL-17, IL-23, and other cytokines to activate T cells, including helper T cell T_H17. Along with other immune cells, T_H17 produces IL-17. This proinflammatory cascade results in keratinocyte proliferation, angiogenesis, and migration of immune cells toward psoriatic lesions.¹ Thus, the newest classes of biologics target IL-12, IL-23, and IL-17 to disrupt this inflammatory cascade.

We provide an updated review of the most recent clinical efficacy and safety data on the newest IL-23 and IL-17 inhibitors in the pipeline or approved for psoriasis, including risankizumab, guselkumab, tildrakizumab, ixekizumab, and brodalumab (Table). Ustekinumab and adalimumab, which have been previously approved by the US Food and Drug Administration (FDA), will be discussed here only as comparators.

IL-23 Inhibitors

Risankizumab

Risankizumab (formerly known as BI 655066)(Boehringer Ingelheim) is a selective human monoclonal antibody targeting the p19 subunit of IL-23 and currently is undergoing phase 3 trials for psoriasis. A proof-of-concept phase 1 study of 39 participants demonstrated efficacy after 12 weeks of treatment at varying subcutaneous and intravenous doses with placebo control.¹¹ At week 12, 87% (27/31)(P<.001) of all risankizumab-treated participants achieved 75% reduction in psoriasis area and severity index (PASI) score compared to 0% of 8 placebo-treated participants. Common adverse effects (AEs) occurred in 65% (20/31) of risankizumab-treated participants, including non–dose-dependent upper respiratory tract infections, nasopharyngitis, and headache. Serious adverse events (SAEs) that occurred were considered unrelated to the study medication.¹¹

A phase 2 trial of 166 participants compared 3 dosing regimens of subcutaneous risankizumab (single 18-mg dose at week 0; single 90-mg dose at weeks 0, 4, and 16; or single 180-mg dose at weeks 0, 4, and 16) and ustekinumab (weight-based single 45- or 90-mg dose at weeks 0, 4, and 16), demonstrating noninferiority at higher doses of risankizumab.² Preliminary primary end point results at week 12 showed PASI 90 in 32.6% (P=.4667), 73.2% (P=.0013), 81.0% (P<.0001), and 40.0% of the treatment groups, respectively. Participants in the 180-mg risankizumab group achieved PASI 90 eight weeks faster than those on ustekinumab, lasting more than 2 months longer. Adverse effects were similar across all treatment groups and SAEs were unrelated to the study medications.²

Guselkumab

Guselkumab (Janssen Biotech, Inc) is a selective human monoclonal antibody against the p19 subunit of IL-23. The 52-week phase 2 X-PLORE trial compared dose-ranging subcutaneous guselkumab (5 mg at weeks 0 and 4, then every 12 weeks; 15 mg every 8 weeks; 50 mg at weeks 0 and 4, then every 12 weeks; 100 mg every 8 weeks; or 200 mg at weeks 0 and 4, then every 12 weeks), adalimumab (80-mg loading dose, followed by 40 mg at week 1, then every other week), and placebo in 293 randomized participants.⁴ At week 16, 34% (P=.002) of participants in the 5-mg guselkumab group, 61% (P<.001) in the 15-mg group, 79% (P<.001) in the 50-mg group, 86% (P<.001) in the 100-mg group, 83% (P<.001) in the 200-mg group, and 58% (P<.001) in the adalimumab group achieved physician global assessment (PGA) scores of 0 (clear) or 1 (minimal psoriasis) compared to 7% of the placebo group. Achievement of PASI 75 similarly favored the guselkumab (44% [P<.001]; 76% [no P value given]; 81% [P<.001]; 79% [P<.001]; and 81% [P<.001], respectively) and adalimumab treatment arms (70% [P<.001]) compared to 5% in the placebo group. In longer-term comparisons to week 40, participants in the 50-, 100-, and 200-mg guselkumab groups showed significantly greater remission of psoriatic lesions, measured by a PGA score of 0 or 1, than participants in the adalimumab group (71% [P=.05]; 77% [P=.005]; 81% [P=.01]; and 49%, respectively).⁴

Preliminary results from VOYAGE 1 (N=837), the first of several phase 3 trials, further demonstrate the superiority of guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks over adalimumab (standard dosing) and placebo; at week 16, 73.3% (P<.001 for both comparisons) versus 49.7% and 2.9% of participants, respectively, achieved PASI 90, with sustained superiority of skin clearance in guselkumab-treated participants compared to adalimumab and placebo through week 48.³

Long-term safety data showed no dose dependence or trend from 0 to 16 weeks and 16 to 52 weeks of treatment regarding rates of AEs, SAEs, or serious infections.⁴ Between weeks 16 and 52, 48.9% of all guselkumab-treated participants exhibited AEs compared to 60.5% of adalimumab-treated participants and 51.3% of placebo participants. Overall infection rates also were lowest in the guselkumab group at 29.8% compared to 36.8% and 35.9%, respectively. Three participants treated with guselkumab had major cardiovascular events, including a fatal myocardial infarction. No cases of tuberculosis or serious opportunistic infections were reported.⁴

Tildrakizumab

Tildrakizumab (formerly known as MK-3222)(Sun Pharmaceutical Industries Ltd) is a human monoclonal antibody also targeting the p19 subunit of IL-23. In a phase 2 study of 355 participants with chronic plaque psoriasis, participants received 5-, 25-, 100-, or 200-mg subcutaneous tildrakizumab or placebo at weeks 0 and 4 and then every 12 weeks for a total of 52 weeks.⁶ At week 16, PASI 75 results were 33.3%, 64.4%, 66.3%, 74.4%, and 4.4%, respectively (P<.001 for each comparison). Improvement began within the first month of treatment, with median times to PASI 75 of 57 days at 200-mg dosing and 84 days at 100-mg dosing. Of those participants achieving PASI 75 by drug discontinuation at week 52, 96% of the 100-mg group and 93% of the 200-mg group maintained PASI 75 through week 72, suggesting low relapse rates after treatment cessation.⁶

In October 2016, the efficacy results of 2 pivotal phase 3 trials (reSURFACE 1 and reSURFACE 2) involving more than 1800 participants combined revealed PASI 90 achievement in an average of 54% of participants on tildrakizumab 100 mg and 59% of participants on tildrakizumab 200 mg at week 28.⁵ Achievement of PASI 100 occurred in 24% and 30% of participants at week 28, respectively. The second of these trials included an etanercept comparison group and demonstrated head-to-head superiority of 100 and 200 mg subcutaneous tildrakizumab at week 12 by end point measures.⁵

Treatment-related AEs occurred at rates of 25% in tildrakizumab-treated participants and 22% in placebo-treated participants, most frequently nasopharyngitis and headache.⁶ At least 1 AE occurred in 64% of tildrakizumab-treated participants without dose dependence compared to 69% of placebo-treated participants. Severe AEs thought to be drug treatment related were bacterial arthritis, lymphedema, melanoma, stroke, and epiglottitis.⁶

IL-17 Inhibitors

Ixekizumab

Ixekizumab (Eli Lilly and Company), a monoclonal inhibitor of IL-17A, is the most recently approved psoriasis biologic on the market and has been cleared for use in adults with moderate to severe plaque psoriasis. Recommended dosing is 160 mg (given in two 80-mg subcutaneous injections via an autoinjector or prefilled syringe) at week 0, followed by an 80-mg injection at weeks 2, 4, 6, 8, 10, and 12, and then 80 mg every 4 weeks thereafter. The FDA approved ixekizumab in March 2016 following favorable results of several phase 3 trials: UNCOVER-1, UNCOVER-2, and UNCOVER-3.^7,8

In UNCOVER-1, 1296 participants were randomized to 1 of 2 ixekizumab treatment arms—160 mg starting dose at week 0, 80 mg every 2 or 4 weeks thereafter—or placebo.⁷ At week 12, 89.1%, 82.6%, and 3.9% achieved PASI 75, respectively (P<.001 for both). Importantly, high numbers of participants also achieved PASI 90 (70.9% in the 2-week group and 64.6% in the 4-week group vs 0.5% in the placebo group [P<.001]) and PASI 100 (35.3% and 33.6% vs 0%, respectively [P<.001]), suggesting high rates of disease clearance.⁷

UNCOVER-2 (N=1224) and UNCOVER-3 (N=1346) investigated the same 2 dosing regimens of ixekizumab compared to etanercept 50 mg biweekly and placebo.⁸ At week 12, the percentage of participants achieving PASI 90 in UNCOVER-2 was 70.7%, 59.7%, 18.7%, and 0.6%, respectively, and 68.1%, 65.3%, 25.7%, and 3.1%, respectively, in UNCOVER-3 (P<.0001 for all comparisons to placebo and etanercept). At week 12, PASI 100 results also showed striking superiority, with 40.5%, 30.8%, 5.3%, and 0.6% of participants, respectively, in UNCOVER-2, and 37.7%, 35%, 7.3%, and 0%, respectively, in UNCOVER-3, achieving complete clearance of disease (P<.0001 for all comparisons to placebo and etanercept). Responses to ixekizumab were observed as early as weeks 1 and 2, while no participants in the etanercept and placebo treatment groups achieved comparative efficiency.⁸

In an extension of UNCOVER-3, efficacy increased from week 12 to week 60 according to PASI 90 (68%–73% in the 2-week group; 65%–72% in the 4-week group) and PASI 100 measures (38%–55% in the 2-week group; 35%–52% in the 4-week group).⁷

The most common AEs associated with ixekizumab treatment from weeks 0 to 12 occurred at higher rates in the 2-week and 4-week ixekizumab groups compared to placebo, including nasopharyngitis (9.5% and 9% vs 8.7%, respectively), upper respiratory tract infection (4.4% and 3.9% vs 3.5%, respectively), injection-site reaction (10% and 7.7% vs 1%, respectively), arthralgia (4.4% and 4.3% vs 2.9%, respectively), and headache (2.5% and 1.9% vs 2.1%, respectively). Infections, including candidal, oral, vulvovaginal, and cutaneous, occurred in 27% of the 2-week dosing group and 27.4% of the 4-week dosing group compared to 22.9% of the placebo group during weeks 0 to 12, with candidal infections in particular occurring more frequently in the active treatment groups and exhibiting dose dependence. Other AEs of special interest that occurred among all ixekizumab-treated participants (n=3736) from weeks 0 to 60 were cardiovascular and cerebrovascular events (22 [0.6%]), inflammatory bowel disease (11 [0.3%]), non–skin cancer malignancy (14 [0.4%]), and nonmelanoma skin cancer (20 [0.5%]). Neutropenia occurred at higher rates in ixekizumab-treated participants (9.3% in the 2-week group and 8.6% in the 4-week group) compared to placebo (3.3%) and occurred in 11.5% of all ixekizumab participants over 60 weeks.⁷

Brodalumab

Brodalumab (Valeant Pharmaceuticals International, Inc) is a human monoclonal antibody targeting the IL-17A receptor currently under review for FDA approval after undergoing phase 3 trials. The first of these trials, AMAGINE-1, showed efficacy of subcutaneous brodalumab (140 or 210 mg administered every 2 weeks with an extra dose at week 1) compared to placebo in 661 participants.⁹ At week 12, 60%, 83%, and 3%, respectively, achieved PASI 75; 43%, 70%, and 1%, respectively, achieved PASI 90; and 23%, 42%, and 1%, respectively, achieved PASI 100 (P<.001 for all respective comparisons to placebo). These effects were retained through 52 weeks of treatment. The median time to complete disease clearance in participants reaching PASI 100 was 12 weeks. Conversely, participants who were re-randomized to placebo after week 12 of brodalumab treatment relapsed within weeks to months.⁹

AMAGINE-2 and AMAGINE-3 further demonstrated the efficacy of brodalumab (140 or 210 mg every 2 weeks with extra dose at week 1) compared to ustekinumab (45 or 90 mg weight-based standard dosing) and placebo in 1831 participants, respectively.¹⁰ In AMAGINE-2, 49% of participants in the 140-mg group (P<.001 vs placebo), 70% in the 210-mg group (P<.001 vs placebo), 47% in the ustekinumab group, and 3% in the placebo group achieved PASI 90 at week 12. Similarly, in AMAGINE-3, 52% of participants in the 140-mg group (P<.001), 69% in the 210-mg group (P<.001), 48% in the ustekinumab group, and 2% in the placebo group achieved PASI 90. Impressively, complete clearance (PASI 100) at week 12 occurred in 26% of the 140-mg group (P<.001 vs placebo), 44% of the 210-mg group (P<.001 vs placebo), and 22% of the ustekinumab group compared to 2% of the placebo group in AMAGINE-2, with similar rates in AMAGINE-3. Brodalumab was significantly superior to ustekinumab at the 210-mg dose by PASI 90 measures (P<.001) in both studies and at the 140-mg dose by PASI 100 measures (P=.007) in AMAGINE-3 only.¹⁰

Common AEs were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia, all occurring at grossly similar rates (49%–60%) across all experimental groups in AMAGINE-1, AMAGINE-2, and AMAGINE-3 during the first 12-week treatment period.^9,10 Brodalumab treatment groups had high rates of specific interest AEs compared to ustekinumab and placebo groups, including neutropenia (0.8%, 1.1%, 0.3%, and 0%, respectively) and candidal infections (0.8%, 1.3%, 0.3%, and 0.3%, respectively). Induction phase (weeks 0–12) depression rates were concerning, with 6 cases each in AMAGINE-2 (4 [0.7%] in the 140-mg group, 2 [0.3%] in the 210-mg group) and AMAGINE-3 (4 [0.6%] in the 140-mg group, 2 [0.3%] in the 210-mg group). Cases of neutropenia were mild, were not associated with major infection, and were transient or reversible. Depression rates after 52 weeks of treatment were 1.7% (23/1567) of brodalumab participants in AMAGINE-2 and 1.8% (21/1613) in AMAGINE-3. Three participants, all on constant 210-mg dosing through week 52, attempted suicide with 1 completion¹⁰; however, because no other IL-17 inhibitors were associated with depression or suicide in other trials, it has been suggested that these cases were incidental and not treatment related.¹² An FDA advisory panel recommended approval of brodalumab in July 2016 despite ongoing concerns of depression and suicide.¹³

Conclusion

The robust investigation into IL-23 and IL-17 inhibitors to treat plaque psoriasis has yielded promising results, including the unprecedented rates of PASI 100 achievement with these new biologics. Risankizumab, ixekizumab, and brodalumab have demonstrated superior efficacy in trials compared to ustekinumab. Tildrakizumab has shown low disease relapse after drug cessation. Ixekizumab and brodalumab have shown high rates of total disease clearance. Thus far, safety findings for these pipeline biologics have been consistent with those of ustekinumab. With ixekizumab approved in 2016 and brodalumab under review, new options in biologic therapy will offer patients and clinicians greater choices in treating severe and recalcitrant psoriasis.

The role of current biologic therapies in psoriasis predicates on the pathogenic role of upregulated, immune-related mechanisms that result in the activation of myeloid dendritic cells, which release IL-17, IL-23, and other cytokines to activate T cells, including helper T cell T_H17. Along with other immune cells, T_H17 produces IL-17. This proinflammatory cascade results in keratinocyte proliferation, angiogenesis, and migration of immune cells toward psoriatic lesions.¹ Thus, the newest classes of biologics target IL-12, IL-23, and IL-17 to disrupt this inflammatory cascade.

We provide an updated review of the most recent clinical efficacy and safety data on the newest IL-23 and IL-17 inhibitors in the pipeline or approved for psoriasis, including risankizumab, guselkumab, tildrakizumab, ixekizumab, and brodalumab (Table). Ustekinumab and adalimumab, which have been previously approved by the US Food and Drug Administration (FDA), will be discussed here only as comparators.

IL-23 Inhibitors

Risankizumab

Risankizumab (formerly known as BI 655066)(Boehringer Ingelheim) is a selective human monoclonal antibody targeting the p19 subunit of IL-23 and currently is undergoing phase 3 trials for psoriasis. A proof-of-concept phase 1 study of 39 participants demonstrated efficacy after 12 weeks of treatment at varying subcutaneous and intravenous doses with placebo control.¹¹ At week 12, 87% (27/31)(P<.001) of all risankizumab-treated participants achieved 75% reduction in psoriasis area and severity index (PASI) score compared to 0% of 8 placebo-treated participants. Common adverse effects (AEs) occurred in 65% (20/31) of risankizumab-treated participants, including non–dose-dependent upper respiratory tract infections, nasopharyngitis, and headache. Serious adverse events (SAEs) that occurred were considered unrelated to the study medication.¹¹

A phase 2 trial of 166 participants compared 3 dosing regimens of subcutaneous risankizumab (single 18-mg dose at week 0; single 90-mg dose at weeks 0, 4, and 16; or single 180-mg dose at weeks 0, 4, and 16) and ustekinumab (weight-based single 45- or 90-mg dose at weeks 0, 4, and 16), demonstrating noninferiority at higher doses of risankizumab.² Preliminary primary end point results at week 12 showed PASI 90 in 32.6% (P=.4667), 73.2% (P=.0013), 81.0% (P<.0001), and 40.0% of the treatment groups, respectively. Participants in the 180-mg risankizumab group achieved PASI 90 eight weeks faster than those on ustekinumab, lasting more than 2 months longer. Adverse effects were similar across all treatment groups and SAEs were unrelated to the study medications.²

Guselkumab

Guselkumab (Janssen Biotech, Inc) is a selective human monoclonal antibody against the p19 subunit of IL-23. The 52-week phase 2 X-PLORE trial compared dose-ranging subcutaneous guselkumab (5 mg at weeks 0 and 4, then every 12 weeks; 15 mg every 8 weeks; 50 mg at weeks 0 and 4, then every 12 weeks; 100 mg every 8 weeks; or 200 mg at weeks 0 and 4, then every 12 weeks), adalimumab (80-mg loading dose, followed by 40 mg at week 1, then every other week), and placebo in 293 randomized participants.⁴ At week 16, 34% (P=.002) of participants in the 5-mg guselkumab group, 61% (P<.001) in the 15-mg group, 79% (P<.001) in the 50-mg group, 86% (P<.001) in the 100-mg group, 83% (P<.001) in the 200-mg group, and 58% (P<.001) in the adalimumab group achieved physician global assessment (PGA) scores of 0 (clear) or 1 (minimal psoriasis) compared to 7% of the placebo group. Achievement of PASI 75 similarly favored the guselkumab (44% [P<.001]; 76% [no P value given]; 81% [P<.001]; 79% [P<.001]; and 81% [P<.001], respectively) and adalimumab treatment arms (70% [P<.001]) compared to 5% in the placebo group. In longer-term comparisons to week 40, participants in the 50-, 100-, and 200-mg guselkumab groups showed significantly greater remission of psoriatic lesions, measured by a PGA score of 0 or 1, than participants in the adalimumab group (71% [P=.05]; 77% [P=.005]; 81% [P=.01]; and 49%, respectively).⁴

Preliminary results from VOYAGE 1 (N=837), the first of several phase 3 trials, further demonstrate the superiority of guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks over adalimumab (standard dosing) and placebo; at week 16, 73.3% (P<.001 for both comparisons) versus 49.7% and 2.9% of participants, respectively, achieved PASI 90, with sustained superiority of skin clearance in guselkumab-treated participants compared to adalimumab and placebo through week 48.³

Long-term safety data showed no dose dependence or trend from 0 to 16 weeks and 16 to 52 weeks of treatment regarding rates of AEs, SAEs, or serious infections.⁴ Between weeks 16 and 52, 48.9% of all guselkumab-treated participants exhibited AEs compared to 60.5% of adalimumab-treated participants and 51.3% of placebo participants. Overall infection rates also were lowest in the guselkumab group at 29.8% compared to 36.8% and 35.9%, respectively. Three participants treated with guselkumab had major cardiovascular events, including a fatal myocardial infarction. No cases of tuberculosis or serious opportunistic infections were reported.⁴

Tildrakizumab

Tildrakizumab (formerly known as MK-3222)(Sun Pharmaceutical Industries Ltd) is a human monoclonal antibody also targeting the p19 subunit of IL-23. In a phase 2 study of 355 participants with chronic plaque psoriasis, participants received 5-, 25-, 100-, or 200-mg subcutaneous tildrakizumab or placebo at weeks 0 and 4 and then every 12 weeks for a total of 52 weeks.⁶ At week 16, PASI 75 results were 33.3%, 64.4%, 66.3%, 74.4%, and 4.4%, respectively (P<.001 for each comparison). Improvement began within the first month of treatment, with median times to PASI 75 of 57 days at 200-mg dosing and 84 days at 100-mg dosing. Of those participants achieving PASI 75 by drug discontinuation at week 52, 96% of the 100-mg group and 93% of the 200-mg group maintained PASI 75 through week 72, suggesting low relapse rates after treatment cessation.⁶

In October 2016, the efficacy results of 2 pivotal phase 3 trials (reSURFACE 1 and reSURFACE 2) involving more than 1800 participants combined revealed PASI 90 achievement in an average of 54% of participants on tildrakizumab 100 mg and 59% of participants on tildrakizumab 200 mg at week 28.⁵ Achievement of PASI 100 occurred in 24% and 30% of participants at week 28, respectively. The second of these trials included an etanercept comparison group and demonstrated head-to-head superiority of 100 and 200 mg subcutaneous tildrakizumab at week 12 by end point measures.⁵

Treatment-related AEs occurred at rates of 25% in tildrakizumab-treated participants and 22% in placebo-treated participants, most frequently nasopharyngitis and headache.⁶ At least 1 AE occurred in 64% of tildrakizumab-treated participants without dose dependence compared to 69% of placebo-treated participants. Severe AEs thought to be drug treatment related were bacterial arthritis, lymphedema, melanoma, stroke, and epiglottitis.⁶

IL-17 Inhibitors

Ixekizumab

Ixekizumab (Eli Lilly and Company), a monoclonal inhibitor of IL-17A, is the most recently approved psoriasis biologic on the market and has been cleared for use in adults with moderate to severe plaque psoriasis. Recommended dosing is 160 mg (given in two 80-mg subcutaneous injections via an autoinjector or prefilled syringe) at week 0, followed by an 80-mg injection at weeks 2, 4, 6, 8, 10, and 12, and then 80 mg every 4 weeks thereafter. The FDA approved ixekizumab in March 2016 following favorable results of several phase 3 trials: UNCOVER-1, UNCOVER-2, and UNCOVER-3.^7,8

In UNCOVER-1, 1296 participants were randomized to 1 of 2 ixekizumab treatment arms—160 mg starting dose at week 0, 80 mg every 2 or 4 weeks thereafter—or placebo.⁷ At week 12, 89.1%, 82.6%, and 3.9% achieved PASI 75, respectively (P<.001 for both). Importantly, high numbers of participants also achieved PASI 90 (70.9% in the 2-week group and 64.6% in the 4-week group vs 0.5% in the placebo group [P<.001]) and PASI 100 (35.3% and 33.6% vs 0%, respectively [P<.001]), suggesting high rates of disease clearance.⁷

UNCOVER-2 (N=1224) and UNCOVER-3 (N=1346) investigated the same 2 dosing regimens of ixekizumab compared to etanercept 50 mg biweekly and placebo.⁸ At week 12, the percentage of participants achieving PASI 90 in UNCOVER-2 was 70.7%, 59.7%, 18.7%, and 0.6%, respectively, and 68.1%, 65.3%, 25.7%, and 3.1%, respectively, in UNCOVER-3 (P<.0001 for all comparisons to placebo and etanercept). At week 12, PASI 100 results also showed striking superiority, with 40.5%, 30.8%, 5.3%, and 0.6% of participants, respectively, in UNCOVER-2, and 37.7%, 35%, 7.3%, and 0%, respectively, in UNCOVER-3, achieving complete clearance of disease (P<.0001 for all comparisons to placebo and etanercept). Responses to ixekizumab were observed as early as weeks 1 and 2, while no participants in the etanercept and placebo treatment groups achieved comparative efficiency.⁸

In an extension of UNCOVER-3, efficacy increased from week 12 to week 60 according to PASI 90 (68%–73% in the 2-week group; 65%–72% in the 4-week group) and PASI 100 measures (38%–55% in the 2-week group; 35%–52% in the 4-week group).⁷

The most common AEs associated with ixekizumab treatment from weeks 0 to 12 occurred at higher rates in the 2-week and 4-week ixekizumab groups compared to placebo, including nasopharyngitis (9.5% and 9% vs 8.7%, respectively), upper respiratory tract infection (4.4% and 3.9% vs 3.5%, respectively), injection-site reaction (10% and 7.7% vs 1%, respectively), arthralgia (4.4% and 4.3% vs 2.9%, respectively), and headache (2.5% and 1.9% vs 2.1%, respectively). Infections, including candidal, oral, vulvovaginal, and cutaneous, occurred in 27% of the 2-week dosing group and 27.4% of the 4-week dosing group compared to 22.9% of the placebo group during weeks 0 to 12, with candidal infections in particular occurring more frequently in the active treatment groups and exhibiting dose dependence. Other AEs of special interest that occurred among all ixekizumab-treated participants (n=3736) from weeks 0 to 60 were cardiovascular and cerebrovascular events (22 [0.6%]), inflammatory bowel disease (11 [0.3%]), non–skin cancer malignancy (14 [0.4%]), and nonmelanoma skin cancer (20 [0.5%]). Neutropenia occurred at higher rates in ixekizumab-treated participants (9.3% in the 2-week group and 8.6% in the 4-week group) compared to placebo (3.3%) and occurred in 11.5% of all ixekizumab participants over 60 weeks.⁷

Brodalumab

Brodalumab (Valeant Pharmaceuticals International, Inc) is a human monoclonal antibody targeting the IL-17A receptor currently under review for FDA approval after undergoing phase 3 trials. The first of these trials, AMAGINE-1, showed efficacy of subcutaneous brodalumab (140 or 210 mg administered every 2 weeks with an extra dose at week 1) compared to placebo in 661 participants.⁹ At week 12, 60%, 83%, and 3%, respectively, achieved PASI 75; 43%, 70%, and 1%, respectively, achieved PASI 90; and 23%, 42%, and 1%, respectively, achieved PASI 100 (P<.001 for all respective comparisons to placebo). These effects were retained through 52 weeks of treatment. The median time to complete disease clearance in participants reaching PASI 100 was 12 weeks. Conversely, participants who were re-randomized to placebo after week 12 of brodalumab treatment relapsed within weeks to months.⁹

AMAGINE-2 and AMAGINE-3 further demonstrated the efficacy of brodalumab (140 or 210 mg every 2 weeks with extra dose at week 1) compared to ustekinumab (45 or 90 mg weight-based standard dosing) and placebo in 1831 participants, respectively.¹⁰ In AMAGINE-2, 49% of participants in the 140-mg group (P<.001 vs placebo), 70% in the 210-mg group (P<.001 vs placebo), 47% in the ustekinumab group, and 3% in the placebo group achieved PASI 90 at week 12. Similarly, in AMAGINE-3, 52% of participants in the 140-mg group (P<.001), 69% in the 210-mg group (P<.001), 48% in the ustekinumab group, and 2% in the placebo group achieved PASI 90. Impressively, complete clearance (PASI 100) at week 12 occurred in 26% of the 140-mg group (P<.001 vs placebo), 44% of the 210-mg group (P<.001 vs placebo), and 22% of the ustekinumab group compared to 2% of the placebo group in AMAGINE-2, with similar rates in AMAGINE-3. Brodalumab was significantly superior to ustekinumab at the 210-mg dose by PASI 90 measures (P<.001) in both studies and at the 140-mg dose by PASI 100 measures (P=.007) in AMAGINE-3 only.¹⁰

Common AEs were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia, all occurring at grossly similar rates (49%–60%) across all experimental groups in AMAGINE-1, AMAGINE-2, and AMAGINE-3 during the first 12-week treatment period.^9,10 Brodalumab treatment groups had high rates of specific interest AEs compared to ustekinumab and placebo groups, including neutropenia (0.8%, 1.1%, 0.3%, and 0%, respectively) and candidal infections (0.8%, 1.3%, 0.3%, and 0.3%, respectively). Induction phase (weeks 0–12) depression rates were concerning, with 6 cases each in AMAGINE-2 (4 [0.7%] in the 140-mg group, 2 [0.3%] in the 210-mg group) and AMAGINE-3 (4 [0.6%] in the 140-mg group, 2 [0.3%] in the 210-mg group). Cases of neutropenia were mild, were not associated with major infection, and were transient or reversible. Depression rates after 52 weeks of treatment were 1.7% (23/1567) of brodalumab participants in AMAGINE-2 and 1.8% (21/1613) in AMAGINE-3. Three participants, all on constant 210-mg dosing through week 52, attempted suicide with 1 completion¹⁰; however, because no other IL-17 inhibitors were associated with depression or suicide in other trials, it has been suggested that these cases were incidental and not treatment related.¹² An FDA advisory panel recommended approval of brodalumab in July 2016 despite ongoing concerns of depression and suicide.¹³

Conclusion

The robust investigation into IL-23 and IL-17 inhibitors to treat plaque psoriasis has yielded promising results, including the unprecedented rates of PASI 100 achievement with these new biologics. Risankizumab, ixekizumab, and brodalumab have demonstrated superior efficacy in trials compared to ustekinumab. Tildrakizumab has shown low disease relapse after drug cessation. Ixekizumab and brodalumab have shown high rates of total disease clearance. Thus far, safety findings for these pipeline biologics have been consistent with those of ustekinumab. With ixekizumab approved in 2016 and brodalumab under review, new options in biologic therapy will offer patients and clinicians greater choices in treating severe and recalcitrant psoriasis.

The role of current biologic therapies in psoriasis predicates on the pathogenic role of upregulated, immune-related mechanisms that result in the activation of myeloid dendritic cells, which release IL-17, IL-23, and other cytokines to activate T cells, including helper T cell T_H17. Along with other immune cells, T_H17 produces IL-17. This proinflammatory cascade results in keratinocyte proliferation, angiogenesis, and migration of immune cells toward psoriatic lesions.¹ Thus, the newest classes of biologics target IL-12, IL-23, and IL-17 to disrupt this inflammatory cascade.

We provide an updated review of the most recent clinical efficacy and safety data on the newest IL-23 and IL-17 inhibitors in the pipeline or approved for psoriasis, including risankizumab, guselkumab, tildrakizumab, ixekizumab, and brodalumab (Table). Ustekinumab and adalimumab, which have been previously approved by the US Food and Drug Administration (FDA), will be discussed here only as comparators.

IL-23 Inhibitors

Risankizumab

Risankizumab (formerly known as BI 655066)(Boehringer Ingelheim) is a selective human monoclonal antibody targeting the p19 subunit of IL-23 and currently is undergoing phase 3 trials for psoriasis. A proof-of-concept phase 1 study of 39 participants demonstrated efficacy after 12 weeks of treatment at varying subcutaneous and intravenous doses with placebo control.¹¹ At week 12, 87% (27/31)(P<.001) of all risankizumab-treated participants achieved 75% reduction in psoriasis area and severity index (PASI) score compared to 0% of 8 placebo-treated participants. Common adverse effects (AEs) occurred in 65% (20/31) of risankizumab-treated participants, including non–dose-dependent upper respiratory tract infections, nasopharyngitis, and headache. Serious adverse events (SAEs) that occurred were considered unrelated to the study medication.¹¹

A phase 2 trial of 166 participants compared 3 dosing regimens of subcutaneous risankizumab (single 18-mg dose at week 0; single 90-mg dose at weeks 0, 4, and 16; or single 180-mg dose at weeks 0, 4, and 16) and ustekinumab (weight-based single 45- or 90-mg dose at weeks 0, 4, and 16), demonstrating noninferiority at higher doses of risankizumab.² Preliminary primary end point results at week 12 showed PASI 90 in 32.6% (P=.4667), 73.2% (P=.0013), 81.0% (P<.0001), and 40.0% of the treatment groups, respectively. Participants in the 180-mg risankizumab group achieved PASI 90 eight weeks faster than those on ustekinumab, lasting more than 2 months longer. Adverse effects were similar across all treatment groups and SAEs were unrelated to the study medications.²

Guselkumab

Guselkumab (Janssen Biotech, Inc) is a selective human monoclonal antibody against the p19 subunit of IL-23. The 52-week phase 2 X-PLORE trial compared dose-ranging subcutaneous guselkumab (5 mg at weeks 0 and 4, then every 12 weeks; 15 mg every 8 weeks; 50 mg at weeks 0 and 4, then every 12 weeks; 100 mg every 8 weeks; or 200 mg at weeks 0 and 4, then every 12 weeks), adalimumab (80-mg loading dose, followed by 40 mg at week 1, then every other week), and placebo in 293 randomized participants.⁴ At week 16, 34% (P=.002) of participants in the 5-mg guselkumab group, 61% (P<.001) in the 15-mg group, 79% (P<.001) in the 50-mg group, 86% (P<.001) in the 100-mg group, 83% (P<.001) in the 200-mg group, and 58% (P<.001) in the adalimumab group achieved physician global assessment (PGA) scores of 0 (clear) or 1 (minimal psoriasis) compared to 7% of the placebo group. Achievement of PASI 75 similarly favored the guselkumab (44% [P<.001]; 76% [no P value given]; 81% [P<.001]; 79% [P<.001]; and 81% [P<.001], respectively) and adalimumab treatment arms (70% [P<.001]) compared to 5% in the placebo group. In longer-term comparisons to week 40, participants in the 50-, 100-, and 200-mg guselkumab groups showed significantly greater remission of psoriatic lesions, measured by a PGA score of 0 or 1, than participants in the adalimumab group (71% [P=.05]; 77% [P=.005]; 81% [P=.01]; and 49%, respectively).⁴

Preliminary results from VOYAGE 1 (N=837), the first of several phase 3 trials, further demonstrate the superiority of guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks over adalimumab (standard dosing) and placebo; at week 16, 73.3% (P<.001 for both comparisons) versus 49.7% and 2.9% of participants, respectively, achieved PASI 90, with sustained superiority of skin clearance in guselkumab-treated participants compared to adalimumab and placebo through week 48.³

Long-term safety data showed no dose dependence or trend from 0 to 16 weeks and 16 to 52 weeks of treatment regarding rates of AEs, SAEs, or serious infections.⁴ Between weeks 16 and 52, 48.9% of all guselkumab-treated participants exhibited AEs compared to 60.5% of adalimumab-treated participants and 51.3% of placebo participants. Overall infection rates also were lowest in the guselkumab group at 29.8% compared to 36.8% and 35.9%, respectively. Three participants treated with guselkumab had major cardiovascular events, including a fatal myocardial infarction. No cases of tuberculosis or serious opportunistic infections were reported.⁴

Tildrakizumab

Tildrakizumab (formerly known as MK-3222)(Sun Pharmaceutical Industries Ltd) is a human monoclonal antibody also targeting the p19 subunit of IL-23. In a phase 2 study of 355 participants with chronic plaque psoriasis, participants received 5-, 25-, 100-, or 200-mg subcutaneous tildrakizumab or placebo at weeks 0 and 4 and then every 12 weeks for a total of 52 weeks.⁶ At week 16, PASI 75 results were 33.3%, 64.4%, 66.3%, 74.4%, and 4.4%, respectively (P<.001 for each comparison). Improvement began within the first month of treatment, with median times to PASI 75 of 57 days at 200-mg dosing and 84 days at 100-mg dosing. Of those participants achieving PASI 75 by drug discontinuation at week 52, 96% of the 100-mg group and 93% of the 200-mg group maintained PASI 75 through week 72, suggesting low relapse rates after treatment cessation.⁶

In October 2016, the efficacy results of 2 pivotal phase 3 trials (reSURFACE 1 and reSURFACE 2) involving more than 1800 participants combined revealed PASI 90 achievement in an average of 54% of participants on tildrakizumab 100 mg and 59% of participants on tildrakizumab 200 mg at week 28.⁵ Achievement of PASI 100 occurred in 24% and 30% of participants at week 28, respectively. The second of these trials included an etanercept comparison group and demonstrated head-to-head superiority of 100 and 200 mg subcutaneous tildrakizumab at week 12 by end point measures.⁵

Treatment-related AEs occurred at rates of 25% in tildrakizumab-treated participants and 22% in placebo-treated participants, most frequently nasopharyngitis and headache.⁶ At least 1 AE occurred in 64% of tildrakizumab-treated participants without dose dependence compared to 69% of placebo-treated participants. Severe AEs thought to be drug treatment related were bacterial arthritis, lymphedema, melanoma, stroke, and epiglottitis.⁶

IL-17 Inhibitors

Ixekizumab

Ixekizumab (Eli Lilly and Company), a monoclonal inhibitor of IL-17A, is the most recently approved psoriasis biologic on the market and has been cleared for use in adults with moderate to severe plaque psoriasis. Recommended dosing is 160 mg (given in two 80-mg subcutaneous injections via an autoinjector or prefilled syringe) at week 0, followed by an 80-mg injection at weeks 2, 4, 6, 8, 10, and 12, and then 80 mg every 4 weeks thereafter. The FDA approved ixekizumab in March 2016 following favorable results of several phase 3 trials: UNCOVER-1, UNCOVER-2, and UNCOVER-3.^7,8

In UNCOVER-1, 1296 participants were randomized to 1 of 2 ixekizumab treatment arms—160 mg starting dose at week 0, 80 mg every 2 or 4 weeks thereafter—or placebo.⁷ At week 12, 89.1%, 82.6%, and 3.9% achieved PASI 75, respectively (P<.001 for both). Importantly, high numbers of participants also achieved PASI 90 (70.9% in the 2-week group and 64.6% in the 4-week group vs 0.5% in the placebo group [P<.001]) and PASI 100 (35.3% and 33.6% vs 0%, respectively [P<.001]), suggesting high rates of disease clearance.⁷

UNCOVER-2 (N=1224) and UNCOVER-3 (N=1346) investigated the same 2 dosing regimens of ixekizumab compared to etanercept 50 mg biweekly and placebo.⁸ At week 12, the percentage of participants achieving PASI 90 in UNCOVER-2 was 70.7%, 59.7%, 18.7%, and 0.6%, respectively, and 68.1%, 65.3%, 25.7%, and 3.1%, respectively, in UNCOVER-3 (P<.0001 for all comparisons to placebo and etanercept). At week 12, PASI 100 results also showed striking superiority, with 40.5%, 30.8%, 5.3%, and 0.6% of participants, respectively, in UNCOVER-2, and 37.7%, 35%, 7.3%, and 0%, respectively, in UNCOVER-3, achieving complete clearance of disease (P<.0001 for all comparisons to placebo and etanercept). Responses to ixekizumab were observed as early as weeks 1 and 2, while no participants in the etanercept and placebo treatment groups achieved comparative efficiency.⁸

In an extension of UNCOVER-3, efficacy increased from week 12 to week 60 according to PASI 90 (68%–73% in the 2-week group; 65%–72% in the 4-week group) and PASI 100 measures (38%–55% in the 2-week group; 35%–52% in the 4-week group).⁷

The most common AEs associated with ixekizumab treatment from weeks 0 to 12 occurred at higher rates in the 2-week and 4-week ixekizumab groups compared to placebo, including nasopharyngitis (9.5% and 9% vs 8.7%, respectively), upper respiratory tract infection (4.4% and 3.9% vs 3.5%, respectively), injection-site reaction (10% and 7.7% vs 1%, respectively), arthralgia (4.4% and 4.3% vs 2.9%, respectively), and headache (2.5% and 1.9% vs 2.1%, respectively). Infections, including candidal, oral, vulvovaginal, and cutaneous, occurred in 27% of the 2-week dosing group and 27.4% of the 4-week dosing group compared to 22.9% of the placebo group during weeks 0 to 12, with candidal infections in particular occurring more frequently in the active treatment groups and exhibiting dose dependence. Other AEs of special interest that occurred among all ixekizumab-treated participants (n=3736) from weeks 0 to 60 were cardiovascular and cerebrovascular events (22 [0.6%]), inflammatory bowel disease (11 [0.3%]), non–skin cancer malignancy (14 [0.4%]), and nonmelanoma skin cancer (20 [0.5%]). Neutropenia occurred at higher rates in ixekizumab-treated participants (9.3% in the 2-week group and 8.6% in the 4-week group) compared to placebo (3.3%) and occurred in 11.5% of all ixekizumab participants over 60 weeks.⁷

Brodalumab

Brodalumab (Valeant Pharmaceuticals International, Inc) is a human monoclonal antibody targeting the IL-17A receptor currently under review for FDA approval after undergoing phase 3 trials. The first of these trials, AMAGINE-1, showed efficacy of subcutaneous brodalumab (140 or 210 mg administered every 2 weeks with an extra dose at week 1) compared to placebo in 661 participants.⁹ At week 12, 60%, 83%, and 3%, respectively, achieved PASI 75; 43%, 70%, and 1%, respectively, achieved PASI 90; and 23%, 42%, and 1%, respectively, achieved PASI 100 (P<.001 for all respective comparisons to placebo). These effects were retained through 52 weeks of treatment. The median time to complete disease clearance in participants reaching PASI 100 was 12 weeks. Conversely, participants who were re-randomized to placebo after week 12 of brodalumab treatment relapsed within weeks to months.⁹

AMAGINE-2 and AMAGINE-3 further demonstrated the efficacy of brodalumab (140 or 210 mg every 2 weeks with extra dose at week 1) compared to ustekinumab (45 or 90 mg weight-based standard dosing) and placebo in 1831 participants, respectively.¹⁰ In AMAGINE-2, 49% of participants in the 140-mg group (P<.001 vs placebo), 70% in the 210-mg group (P<.001 vs placebo), 47% in the ustekinumab group, and 3% in the placebo group achieved PASI 90 at week 12. Similarly, in AMAGINE-3, 52% of participants in the 140-mg group (P<.001), 69% in the 210-mg group (P<.001), 48% in the ustekinumab group, and 2% in the placebo group achieved PASI 90. Impressively, complete clearance (PASI 100) at week 12 occurred in 26% of the 140-mg group (P<.001 vs placebo), 44% of the 210-mg group (P<.001 vs placebo), and 22% of the ustekinumab group compared to 2% of the placebo group in AMAGINE-2, with similar rates in AMAGINE-3. Brodalumab was significantly superior to ustekinumab at the 210-mg dose by PASI 90 measures (P<.001) in both studies and at the 140-mg dose by PASI 100 measures (P=.007) in AMAGINE-3 only.¹⁰

Common AEs were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia, all occurring at grossly similar rates (49%–60%) across all experimental groups in AMAGINE-1, AMAGINE-2, and AMAGINE-3 during the first 12-week treatment period.^9,10 Brodalumab treatment groups had high rates of specific interest AEs compared to ustekinumab and placebo groups, including neutropenia (0.8%, 1.1%, 0.3%, and 0%, respectively) and candidal infections (0.8%, 1.3%, 0.3%, and 0.3%, respectively). Induction phase (weeks 0–12) depression rates were concerning, with 6 cases each in AMAGINE-2 (4 [0.7%] in the 140-mg group, 2 [0.3%] in the 210-mg group) and AMAGINE-3 (4 [0.6%] in the 140-mg group, 2 [0.3%] in the 210-mg group). Cases of neutropenia were mild, were not associated with major infection, and were transient or reversible. Depression rates after 52 weeks of treatment were 1.7% (23/1567) of brodalumab participants in AMAGINE-2 and 1.8% (21/1613) in AMAGINE-3. Three participants, all on constant 210-mg dosing through week 52, attempted suicide with 1 completion¹⁰; however, because no other IL-17 inhibitors were associated with depression or suicide in other trials, it has been suggested that these cases were incidental and not treatment related.¹² An FDA advisory panel recommended approval of brodalumab in July 2016 despite ongoing concerns of depression and suicide.¹³

Conclusion

The robust investigation into IL-23 and IL-17 inhibitors to treat plaque psoriasis has yielded promising results, including the unprecedented rates of PASI 100 achievement with these new biologics. Risankizumab, ixekizumab, and brodalumab have demonstrated superior efficacy in trials compared to ustekinumab. Tildrakizumab has shown low disease relapse after drug cessation. Ixekizumab and brodalumab have shown high rates of total disease clearance. Thus far, safety findings for these pipeline biologics have been consistent with those of ustekinumab. With ixekizumab approved in 2016 and brodalumab under review, new options in biologic therapy will offer patients and clinicians greater choices in treating severe and recalcitrant psoriasis.

WAILEA, Hawaii – The first approval of a biologic for pediatric psoriasis, and ongoing clinical trials of other biologics in children with psoriasis, are among the encouraging therapeutic developments for this patient population, Wynnis Tom, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“We are incredibly excited ... as pediatric dermatologists that we’re finally seeing breakthroughs” in terms of Food and Drug Administration activity regarding the use of biologics for treating psoriasis in children, Dr. Tom said in a video interview at the seminar.

Etanercept (Enbrel) is now approved for children with psoriasis, the first biologic indicated for pediatric psoriasis, and clinical trials of other biologics that have been available for adults and nonbiologic products for pediatric psoriasis are underway, she said.

However, getting insurance coverage can still be a challenge, although having long-term efficacy and safety data helps, noted Dr. Tom of the department of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego. Also helpful is sending letters to insurers on behalf of the patient, describing the patient’s quality of life, descriptions of treatments that have been unsuccessful, and even photos documenting the disease in the child, she added.

Dr. Tom disclosed ties with Promius, Celgene, and Janssen.

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

WAILEA, Hawaii – The first approval of a biologic for pediatric psoriasis, and ongoing clinical trials of other biologics in children with psoriasis, are among the encouraging therapeutic developments for this patient population, Wynnis Tom, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“We are incredibly excited ... as pediatric dermatologists that we’re finally seeing breakthroughs” in terms of Food and Drug Administration activity regarding the use of biologics for treating psoriasis in children, Dr. Tom said in a video interview at the seminar.

Etanercept (Enbrel) is now approved for children with psoriasis, the first biologic indicated for pediatric psoriasis, and clinical trials of other biologics that have been available for adults and nonbiologic products for pediatric psoriasis are underway, she said.

However, getting insurance coverage can still be a challenge, although having long-term efficacy and safety data helps, noted Dr. Tom of the department of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego. Also helpful is sending letters to insurers on behalf of the patient, describing the patient’s quality of life, descriptions of treatments that have been unsuccessful, and even photos documenting the disease in the child, she added.

Dr. Tom disclosed ties with Promius, Celgene, and Janssen.

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

WAILEA, Hawaii – The first approval of a biologic for pediatric psoriasis, and ongoing clinical trials of other biologics in children with psoriasis, are among the encouraging therapeutic developments for this patient population, Wynnis Tom, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“We are incredibly excited ... as pediatric dermatologists that we’re finally seeing breakthroughs” in terms of Food and Drug Administration activity regarding the use of biologics for treating psoriasis in children, Dr. Tom said in a video interview at the seminar.

Etanercept (Enbrel) is now approved for children with psoriasis, the first biologic indicated for pediatric psoriasis, and clinical trials of other biologics that have been available for adults and nonbiologic products for pediatric psoriasis are underway, she said.

However, getting insurance coverage can still be a challenge, although having long-term efficacy and safety data helps, noted Dr. Tom of the department of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego. Also helpful is sending letters to insurers on behalf of the patient, describing the patient’s quality of life, descriptions of treatments that have been unsuccessful, and even photos documenting the disease in the child, she added.

Dr. Tom disclosed ties with Promius, Celgene, and Janssen.

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

The cardiovascular comorbidities associated with psoriasis have been well documented; however, the mechanism by which psoriasis increases the risk for cardiovascular disease (CVD) remains unclear. Elevated systemic inflammatory cytokines and mediators may play a key role in their association, which prompts the questions: Do systemic medications have a protective effect? Do patients on systemic antipsoriatic treatment have a decreased risk for major adverse cardiovascular events (MACEs) compared with untreated patients?

We believe the shared inflammatory processes involved in psoriasis and atherosclerosis formation are potential targets for therapy in reducing the incidence of CVD and its associated complications. A growing amount of evidence suggests cardioprotective effects associated with antipsoriatic treatments such as tumor necrosis factor (TNF) inhibitors and methotrexate. Gkalpakiotis et al¹ demonstrated a reduction in serum E-selectin (mean [standard deviation], 53.04 [23.54] ng/mL vs 35.32 [8.70] ng/mL; P<.001) and IL-22 (25.11 [19.9] pg/mL vs 12.83 [8.42] pg/mL; P<.001) after 3 months of adalimumab administration in patients with moderate to severe psoriasis. Both E-selectin and IL-22 are associated with the development of atherosclerosis, endothelial dysfunction, and an increased incidence of CVD. Similarly, Wu et al² demonstrated a statistically significant reduction (–5.04 mg/dL [95% confidence interval [CI], –8.24 to –2.12; P<.01) in C-reactive protein in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis after concurrent use of methotrexate and TNF inhibitors.

Solomon et al³ compared the rate of newly diagnosed diabetes mellitus among psoriasis and rheumatoid arthritis patients treated with TNF inhibitors, methotrexate, hydroxychloroquine, and other nonbiologic disease-modifying antirheumatic drugs. The authors’ findings suggest that those who take a TNF inhibitor (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91) and hydroxychloroquine (HR, 0.54; 95% CI, 0.36-0.80) are at lower risk for diabetes mellitus compared to those treated with nonbiologic disease-modifying antirheumatic drugs. Conversely, the methotrexate (HR, 0.77; 95% CI, 0.53-1.13) cohort did not show a statistically significant reduction in diabetes risk.³

Pina et al⁴ revealed improvement in endothelial function after 6 months of adalimumab use in patients with moderate to severe psoriasis. To evaluate the presence of subclinical endothelial dysfunction, the authors assessed brachial artery reactivity by measuring flow-mediated dilation and carotid artery stiffness by pulse wave velocity. Patients showed an increase in flow-mediated dilation (mean [SD], 6.19% [2.44%] vs 7.46% [2.43%]; P=.008) and reduction in pulse wave velocity (6.28 [1.04] m/s vs 5.69 [1.31] m/s; P=.03) compared to baseline measurements, indicating an improvement of endothelial function.⁴

Ahlehoff et al⁵ observed for improvements in subclinical left ventricular dysfunction in psoriasis patients after treatment with biologics. Using echocardiography, they assessed for changes in diastolic function and left ventricular systolic deformation (defined by global longitudinal strain). Of patients who received 3 months of biologic therapy (TNF inhibitor orIL-12/23 inhibitor) and maintained at minimum a psoriasis area and severity index 50 response, all demonstrated an improvement in diastolic function (mean [SD], 8.1 [2.1] vs 6.7 [1.9]; P<.001) and global longitudinal strain (mean [SD], –16.8% [2.1%] vs –18.3% [2.3%]; P<.001). Of note, patients who did not achieve a psoriasis area and severity index 50 response at follow-up did not exhibit an improvement in subclinical myocardial function.⁵

Moreover, a Danish nationwide study with up to 5-year follow-up evaluated the risk for MACE (ie, cardiovascular death, myocardial infarction, stroke) in patients with severe psoriasis receiving systemic anti-inflammatory medications and nonsystemic therapies including topical treatments, phototherapy, and climate therapy.⁶ Compared to nonsystemic therapies, methotrexate use (HR, 0.53; 95% CI, 0.34-0.83) was associated with a decreased risk for cardiovascular events. However, a protective decreased risk was not found among patients who used systemic cyclosporine (HR, 1.06; 95% CI, 0.26-4.27) or retinoids (HR, 1.80; 95% CI, 1.03-2.96). Any biological drug use had a comparable but nonsignificant reduction of cardiovascular events (HR, 0.58; 95% CI, 0.30-1.10). After multivariable adjustment, TNF inhibitors were associated with a statistically significant decreased risk for cardiovascular events (HR, 0.46; 95% CI, 0.22-0.98; P=.04) compared to nonsystemic therapies. The IL-12/23 inhibitor did not demonstrate this relationship (HR, 1.52; 95% CI, 0.47-4.94).⁶

Lastly, Wu et al⁷ compared the risk for MACE (ie, myocardial infarction, stroke, unstable angina, transient ischemic attack) between patients with psoriasis who received TNF inhibitors or methotrexate. The TNF inhibitor and methotrexate cohorts were observed for a median of 12 months and 9 months, respectively. After adjusting for potential confounding factors, they found a 45% reduction (HR, 0.55; 95% CI, 0.45-0.67) in cardiovascular event risk in the TNF inhibitor cohort compared with the methotrexate cohort. Notably, analyses also showed comparatively fewer cardiovascular events in the TNF inhibitor cohort throughout all time points—6, 12, 18, 24, 60 months—in the observation period. Regression analysis revealed an 11% reduction in cardiovascular events (HR, 0.89; 95% CI, 0.80-0.98) with each additional 6 months of cumulative TNF inhibitor exposure.

The current sum of evidence suggests cardioprotective effects of TNF inhibitor and methotrexate use. However, given the cumulative systemic toxicity and inferior cutaneous efficacy of methotrexate, TNF inhibitors will likely play a more significant role going forward. The role of methotrexate may be for its simultaneous use with biologic therapies to limit immunogenicity. Newer biologic agents such as IL-12/23 and IL-17 inhibitors have not yet been as extensively studied for their effects on cardiovascular risk as their TNF inhibitor counterparts. However, because of their shared ability to target specific immunological pathways, it is plausible that IL-12/23 and IL-17 agents may exhibit cardioprotective effects.⁸

Patients with psoriasis should be counseled and educated about the increased risk for CVD and its associated morbidity and mortality risk. Screening for modifiable risk factors and recommending therapeutic lifestyle changes also is appropriate. Future studies should help define the role of specific systemic drugs in reducing the risk for CVD in patients with psoriasis. Despite the expanding amount of evidence in the current literature implicating the use of TNF inhibitors for cardiovascular risk prevention, there is still a need for long-term, randomized, placebo-controlled trials to provide more authoritative evidence-based recommendations.

The cardiovascular comorbidities associated with psoriasis have been well documented; however, the mechanism by which psoriasis increases the risk for cardiovascular disease (CVD) remains unclear. Elevated systemic inflammatory cytokines and mediators may play a key role in their association, which prompts the questions: Do systemic medications have a protective effect? Do patients on systemic antipsoriatic treatment have a decreased risk for major adverse cardiovascular events (MACEs) compared with untreated patients?

We believe the shared inflammatory processes involved in psoriasis and atherosclerosis formation are potential targets for therapy in reducing the incidence of CVD and its associated complications. A growing amount of evidence suggests cardioprotective effects associated with antipsoriatic treatments such as tumor necrosis factor (TNF) inhibitors and methotrexate. Gkalpakiotis et al¹ demonstrated a reduction in serum E-selectin (mean [standard deviation], 53.04 [23.54] ng/mL vs 35.32 [8.70] ng/mL; P<.001) and IL-22 (25.11 [19.9] pg/mL vs 12.83 [8.42] pg/mL; P<.001) after 3 months of adalimumab administration in patients with moderate to severe psoriasis. Both E-selectin and IL-22 are associated with the development of atherosclerosis, endothelial dysfunction, and an increased incidence of CVD. Similarly, Wu et al² demonstrated a statistically significant reduction (–5.04 mg/dL [95% confidence interval [CI], –8.24 to –2.12; P<.01) in C-reactive protein in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis after concurrent use of methotrexate and TNF inhibitors.

Solomon et al³ compared the rate of newly diagnosed diabetes mellitus among psoriasis and rheumatoid arthritis patients treated with TNF inhibitors, methotrexate, hydroxychloroquine, and other nonbiologic disease-modifying antirheumatic drugs. The authors’ findings suggest that those who take a TNF inhibitor (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91) and hydroxychloroquine (HR, 0.54; 95% CI, 0.36-0.80) are at lower risk for diabetes mellitus compared to those treated with nonbiologic disease-modifying antirheumatic drugs. Conversely, the methotrexate (HR, 0.77; 95% CI, 0.53-1.13) cohort did not show a statistically significant reduction in diabetes risk.³

Pina et al⁴ revealed improvement in endothelial function after 6 months of adalimumab use in patients with moderate to severe psoriasis. To evaluate the presence of subclinical endothelial dysfunction, the authors assessed brachial artery reactivity by measuring flow-mediated dilation and carotid artery stiffness by pulse wave velocity. Patients showed an increase in flow-mediated dilation (mean [SD], 6.19% [2.44%] vs 7.46% [2.43%]; P=.008) and reduction in pulse wave velocity (6.28 [1.04] m/s vs 5.69 [1.31] m/s; P=.03) compared to baseline measurements, indicating an improvement of endothelial function.⁴

Ahlehoff et al⁵ observed for improvements in subclinical left ventricular dysfunction in psoriasis patients after treatment with biologics. Using echocardiography, they assessed for changes in diastolic function and left ventricular systolic deformation (defined by global longitudinal strain). Of patients who received 3 months of biologic therapy (TNF inhibitor orIL-12/23 inhibitor) and maintained at minimum a psoriasis area and severity index 50 response, all demonstrated an improvement in diastolic function (mean [SD], 8.1 [2.1] vs 6.7 [1.9]; P<.001) and global longitudinal strain (mean [SD], –16.8% [2.1%] vs –18.3% [2.3%]; P<.001). Of note, patients who did not achieve a psoriasis area and severity index 50 response at follow-up did not exhibit an improvement in subclinical myocardial function.⁵

Moreover, a Danish nationwide study with up to 5-year follow-up evaluated the risk for MACE (ie, cardiovascular death, myocardial infarction, stroke) in patients with severe psoriasis receiving systemic anti-inflammatory medications and nonsystemic therapies including topical treatments, phototherapy, and climate therapy.⁶ Compared to nonsystemic therapies, methotrexate use (HR, 0.53; 95% CI, 0.34-0.83) was associated with a decreased risk for cardiovascular events. However, a protective decreased risk was not found among patients who used systemic cyclosporine (HR, 1.06; 95% CI, 0.26-4.27) or retinoids (HR, 1.80; 95% CI, 1.03-2.96). Any biological drug use had a comparable but nonsignificant reduction of cardiovascular events (HR, 0.58; 95% CI, 0.30-1.10). After multivariable adjustment, TNF inhibitors were associated with a statistically significant decreased risk for cardiovascular events (HR, 0.46; 95% CI, 0.22-0.98; P=.04) compared to nonsystemic therapies. The IL-12/23 inhibitor did not demonstrate this relationship (HR, 1.52; 95% CI, 0.47-4.94).⁶

Lastly, Wu et al⁷ compared the risk for MACE (ie, myocardial infarction, stroke, unstable angina, transient ischemic attack) between patients with psoriasis who received TNF inhibitors or methotrexate. The TNF inhibitor and methotrexate cohorts were observed for a median of 12 months and 9 months, respectively. After adjusting for potential confounding factors, they found a 45% reduction (HR, 0.55; 95% CI, 0.45-0.67) in cardiovascular event risk in the TNF inhibitor cohort compared with the methotrexate cohort. Notably, analyses also showed comparatively fewer cardiovascular events in the TNF inhibitor cohort throughout all time points—6, 12, 18, 24, 60 months—in the observation period. Regression analysis revealed an 11% reduction in cardiovascular events (HR, 0.89; 95% CI, 0.80-0.98) with each additional 6 months of cumulative TNF inhibitor exposure.

The current sum of evidence suggests cardioprotective effects of TNF inhibitor and methotrexate use. However, given the cumulative systemic toxicity and inferior cutaneous efficacy of methotrexate, TNF inhibitors will likely play a more significant role going forward. The role of methotrexate may be for its simultaneous use with biologic therapies to limit immunogenicity. Newer biologic agents such as IL-12/23 and IL-17 inhibitors have not yet been as extensively studied for their effects on cardiovascular risk as their TNF inhibitor counterparts. However, because of their shared ability to target specific immunological pathways, it is plausible that IL-12/23 and IL-17 agents may exhibit cardioprotective effects.⁸

Patients with psoriasis should be counseled and educated about the increased risk for CVD and its associated morbidity and mortality risk. Screening for modifiable risk factors and recommending therapeutic lifestyle changes also is appropriate. Future studies should help define the role of specific systemic drugs in reducing the risk for CVD in patients with psoriasis. Despite the expanding amount of evidence in the current literature implicating the use of TNF inhibitors for cardiovascular risk prevention, there is still a need for long-term, randomized, placebo-controlled trials to provide more authoritative evidence-based recommendations.

The cardiovascular comorbidities associated with psoriasis have been well documented; however, the mechanism by which psoriasis increases the risk for cardiovascular disease (CVD) remains unclear. Elevated systemic inflammatory cytokines and mediators may play a key role in their association, which prompts the questions: Do systemic medications have a protective effect? Do patients on systemic antipsoriatic treatment have a decreased risk for major adverse cardiovascular events (MACEs) compared with untreated patients?

We believe the shared inflammatory processes involved in psoriasis and atherosclerosis formation are potential targets for therapy in reducing the incidence of CVD and its associated complications. A growing amount of evidence suggests cardioprotective effects associated with antipsoriatic treatments such as tumor necrosis factor (TNF) inhibitors and methotrexate. Gkalpakiotis et al¹ demonstrated a reduction in serum E-selectin (mean [standard deviation], 53.04 [23.54] ng/mL vs 35.32 [8.70] ng/mL; P<.001) and IL-22 (25.11 [19.9] pg/mL vs 12.83 [8.42] pg/mL; P<.001) after 3 months of adalimumab administration in patients with moderate to severe psoriasis. Both E-selectin and IL-22 are associated with the development of atherosclerosis, endothelial dysfunction, and an increased incidence of CVD. Similarly, Wu et al² demonstrated a statistically significant reduction (–5.04 mg/dL [95% confidence interval [CI], –8.24 to –2.12; P<.01) in C-reactive protein in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis after concurrent use of methotrexate and TNF inhibitors.

Solomon et al³ compared the rate of newly diagnosed diabetes mellitus among psoriasis and rheumatoid arthritis patients treated with TNF inhibitors, methotrexate, hydroxychloroquine, and other nonbiologic disease-modifying antirheumatic drugs. The authors’ findings suggest that those who take a TNF inhibitor (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91) and hydroxychloroquine (HR, 0.54; 95% CI, 0.36-0.80) are at lower risk for diabetes mellitus compared to those treated with nonbiologic disease-modifying antirheumatic drugs. Conversely, the methotrexate (HR, 0.77; 95% CI, 0.53-1.13) cohort did not show a statistically significant reduction in diabetes risk.³

Pina et al⁴ revealed improvement in endothelial function after 6 months of adalimumab use in patients with moderate to severe psoriasis. To evaluate the presence of subclinical endothelial dysfunction, the authors assessed brachial artery reactivity by measuring flow-mediated dilation and carotid artery stiffness by pulse wave velocity. Patients showed an increase in flow-mediated dilation (mean [SD], 6.19% [2.44%] vs 7.46% [2.43%]; P=.008) and reduction in pulse wave velocity (6.28 [1.04] m/s vs 5.69 [1.31] m/s; P=.03) compared to baseline measurements, indicating an improvement of endothelial function.⁴

Ahlehoff et al⁵ observed for improvements in subclinical left ventricular dysfunction in psoriasis patients after treatment with biologics. Using echocardiography, they assessed for changes in diastolic function and left ventricular systolic deformation (defined by global longitudinal strain). Of patients who received 3 months of biologic therapy (TNF inhibitor orIL-12/23 inhibitor) and maintained at minimum a psoriasis area and severity index 50 response, all demonstrated an improvement in diastolic function (mean [SD], 8.1 [2.1] vs 6.7 [1.9]; P<.001) and global longitudinal strain (mean [SD], –16.8% [2.1%] vs –18.3% [2.3%]; P<.001). Of note, patients who did not achieve a psoriasis area and severity index 50 response at follow-up did not exhibit an improvement in subclinical myocardial function.⁵

Moreover, a Danish nationwide study with up to 5-year follow-up evaluated the risk for MACE (ie, cardiovascular death, myocardial infarction, stroke) in patients with severe psoriasis receiving systemic anti-inflammatory medications and nonsystemic therapies including topical treatments, phototherapy, and climate therapy.⁶ Compared to nonsystemic therapies, methotrexate use (HR, 0.53; 95% CI, 0.34-0.83) was associated with a decreased risk for cardiovascular events. However, a protective decreased risk was not found among patients who used systemic cyclosporine (HR, 1.06; 95% CI, 0.26-4.27) or retinoids (HR, 1.80; 95% CI, 1.03-2.96). Any biological drug use had a comparable but nonsignificant reduction of cardiovascular events (HR, 0.58; 95% CI, 0.30-1.10). After multivariable adjustment, TNF inhibitors were associated with a statistically significant decreased risk for cardiovascular events (HR, 0.46; 95% CI, 0.22-0.98; P=.04) compared to nonsystemic therapies. The IL-12/23 inhibitor did not demonstrate this relationship (HR, 1.52; 95% CI, 0.47-4.94).⁶

Lastly, Wu et al⁷ compared the risk for MACE (ie, myocardial infarction, stroke, unstable angina, transient ischemic attack) between patients with psoriasis who received TNF inhibitors or methotrexate. The TNF inhibitor and methotrexate cohorts were observed for a median of 12 months and 9 months, respectively. After adjusting for potential confounding factors, they found a 45% reduction (HR, 0.55; 95% CI, 0.45-0.67) in cardiovascular event risk in the TNF inhibitor cohort compared with the methotrexate cohort. Notably, analyses also showed comparatively fewer cardiovascular events in the TNF inhibitor cohort throughout all time points—6, 12, 18, 24, 60 months—in the observation period. Regression analysis revealed an 11% reduction in cardiovascular events (HR, 0.89; 95% CI, 0.80-0.98) with each additional 6 months of cumulative TNF inhibitor exposure.

The current sum of evidence suggests cardioprotective effects of TNF inhibitor and methotrexate use. However, given the cumulative systemic toxicity and inferior cutaneous efficacy of methotrexate, TNF inhibitors will likely play a more significant role going forward. The role of methotrexate may be for its simultaneous use with biologic therapies to limit immunogenicity. Newer biologic agents such as IL-12/23 and IL-17 inhibitors have not yet been as extensively studied for their effects on cardiovascular risk as their TNF inhibitor counterparts. However, because of their shared ability to target specific immunological pathways, it is plausible that IL-12/23 and IL-17 agents may exhibit cardioprotective effects.⁸

Patients with psoriasis should be counseled and educated about the increased risk for CVD and its associated morbidity and mortality risk. Screening for modifiable risk factors and recommending therapeutic lifestyle changes also is appropriate. Future studies should help define the role of specific systemic drugs in reducing the risk for CVD in patients with psoriasis. Despite the expanding amount of evidence in the current literature implicating the use of TNF inhibitors for cardiovascular risk prevention, there is still a need for long-term, randomized, placebo-controlled trials to provide more authoritative evidence-based recommendations.

WAILEA, Hawaii – Combining methotrexate with a biologic is an off-label use for psoriasis patients but is supported by information from the psoriatic arthritis literature, said J. Mark Jackson, MD, of the University of Louisville (Ky.).

In fact, the combination treatment may improve symptoms in patients with both psoriasis and arthritis not well controlled with one drug, Dr. Jackson explained in a video interview at the meeting, provided by Global Academy for Medical Education/Skin Disease Education Foundation.

As for dosage, “I do think we can use less methotrexate in combination” with a biologic for psoriasis when using methotrexate alone, he noted. “It’s like the addition of a spice to the right dish,” he added. Patients may need “just a little bit to get them over the edge and really get them to that efficacy point that creates the success that you need.”

Dr. Jackson disclosed financial relationships with companies including AbbVie, Amgen, Celgene, Dermira, Galderma, Genentech, Janssen, Lilly, Medimetriks, Merck, Novartis, Pfizer, Promius, and Top MD.

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

WAILEA, Hawaii – Combining methotrexate with a biologic is an off-label use for psoriasis patients but is supported by information from the psoriatic arthritis literature, said J. Mark Jackson, MD, of the University of Louisville (Ky.).

In fact, the combination treatment may improve symptoms in patients with both psoriasis and arthritis not well controlled with one drug, Dr. Jackson explained in a video interview at the meeting, provided by Global Academy for Medical Education/Skin Disease Education Foundation.

As for dosage, “I do think we can use less methotrexate in combination” with a biologic for psoriasis when using methotrexate alone, he noted. “It’s like the addition of a spice to the right dish,” he added. Patients may need “just a little bit to get them over the edge and really get them to that efficacy point that creates the success that you need.”

Dr. Jackson disclosed financial relationships with companies including AbbVie, Amgen, Celgene, Dermira, Galderma, Genentech, Janssen, Lilly, Medimetriks, Merck, Novartis, Pfizer, Promius, and Top MD.

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

WAILEA, Hawaii – Combining methotrexate with a biologic is an off-label use for psoriasis patients but is supported by information from the psoriatic arthritis literature, said J. Mark Jackson, MD, of the University of Louisville (Ky.).

In fact, the combination treatment may improve symptoms in patients with both psoriasis and arthritis not well controlled with one drug, Dr. Jackson explained in a video interview at the meeting, provided by Global Academy for Medical Education/Skin Disease Education Foundation.

As for dosage, “I do think we can use less methotrexate in combination” with a biologic for psoriasis when using methotrexate alone, he noted. “It’s like the addition of a spice to the right dish,” he added. Patients may need “just a little bit to get them over the edge and really get them to that efficacy point that creates the success that you need.”

Dr. Jackson disclosed financial relationships with companies including AbbVie, Amgen, Celgene, Dermira, Galderma, Genentech, Janssen, Lilly, Medimetriks, Merck, Novartis, Pfizer, Promius, and Top MD.

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

WAILEA, Hawaii – Biosimilars are coming to dermatology, but their impact from a clinical and insurance standpoint has yet to be determined, according to Kenneth B. Gordon, MD, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

Biosimilars seem to have reasonably good efficacy, and safety to date has been “pretty consistent” with safety associated with the parent compounds, but a key issue will be how they are used in patients on anti-TNF agents who have been doing well over time, Dr. Gordon said in a video interview. Because these medicines cross react in terms of immunogenicity and are not quite the same, “trying to use them interchangeably, as many insurance companies will ask us to do, is going to be difficult,” he noted.

His concern does not apply to a new patient starting on a biosimilar. “The problem I see is when insurance companies and pharmacies start mandating us going back and forth between medicines, and running into difficulty with loss of effect of those drugs,” he explained. “It’s not a safety issue, it’s more of an issue of losing efficacy of a formerly active drug,” he said at the meeting provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. Gordon disclosed financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Janssen, Lilly, Celgene, Novartis, and Sun.

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

WAILEA, Hawaii – Biosimilars are coming to dermatology, but their impact from a clinical and insurance standpoint has yet to be determined, according to Kenneth B. Gordon, MD, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

Biosimilars seem to have reasonably good efficacy, and safety to date has been “pretty consistent” with safety associated with the parent compounds, but a key issue will be how they are used in patients on anti-TNF agents who have been doing well over time, Dr. Gordon said in a video interview. Because these medicines cross react in terms of immunogenicity and are not quite the same, “trying to use them interchangeably, as many insurance companies will ask us to do, is going to be difficult,” he noted.

His concern does not apply to a new patient starting on a biosimilar. “The problem I see is when insurance companies and pharmacies start mandating us going back and forth between medicines, and running into difficulty with loss of effect of those drugs,” he explained. “It’s not a safety issue, it’s more of an issue of losing efficacy of a formerly active drug,” he said at the meeting provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. Gordon disclosed financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Janssen, Lilly, Celgene, Novartis, and Sun.

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

WAILEA, Hawaii – Biosimilars are coming to dermatology, but their impact from a clinical and insurance standpoint has yet to be determined, according to Kenneth B. Gordon, MD, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

Biosimilars seem to have reasonably good efficacy, and safety to date has been “pretty consistent” with safety associated with the parent compounds, but a key issue will be how they are used in patients on anti-TNF agents who have been doing well over time, Dr. Gordon said in a video interview. Because these medicines cross react in terms of immunogenicity and are not quite the same, “trying to use them interchangeably, as many insurance companies will ask us to do, is going to be difficult,” he noted.

His concern does not apply to a new patient starting on a biosimilar. “The problem I see is when insurance companies and pharmacies start mandating us going back and forth between medicines, and running into difficulty with loss of effect of those drugs,” he explained. “It’s not a safety issue, it’s more of an issue of losing efficacy of a formerly active drug,” he said at the meeting provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. Gordon disclosed financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Janssen, Lilly, Celgene, Novartis, and Sun.

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