Psoriasis Collection

Despite following guidelines aimed at reducing the likelihood of tuberculosis infection in patients with psoriasis treated with tumor necrosis factor antagonists, a French study has identified a number of active TB cases in this patient group.

The nationwide retrospective study identified 12 cases of tuberculosis in individuals with psoriasis during treatment with a TNF-antagonist between 2006 and 2014 – 9 men and 3 women, whose mean age was 49 years – according to Dr. E. Guinard of the dermatology service, CHU Toulouse Larrey at Paul Sabatier University, Toulouse, France, and associates (J Eur Acad Dermatol Venereol. 2016 Jun 3. doi: 10.1111/jdv.13633).

The investigators identified the cases from a national pharmacosurveillance database and by contacting members of the psoriasis research group in France’s national dermatology society and the national college of French dermatology professors.

Before starting anti-TNF therapy, all 12 patients had been screened for latent TB based on French guidelines: three patients were tested with the tuberculosis skin test alone, six were tested with QuantiFERON-TB Gold test, and three patients had both the skin test and QuantiFERON-TB. Each had a pretreatment chest x-ray.

Based on this testing, three were diagnosed with latent TB and received chemoprophylaxis; the other nine patients tested negative.

Information on TB risk factors was not available for all 12 cases, but three people had had contact with someone with TB during treatment. Three of the individuals had traveled to or were born in areas where TB was endemic, and one patient had had a case of TB in the family in the year before starting anti-TNF therapy. Nine patients had a known history of BCG vaccination, the investigators said.

The time between starting anti-TNF therapy and the appearance of TB symptoms ranged from 2 to 176 weeks (mean, 23 weeks), and diagnosis was based on clinical signs – such as fever, night sweats, and cough – and on imaging and laboratory investigations. Most (10) of the cases were extrapulmonary presentations, and two were pleuropulmonary. When diagnosed with tuberculosis, seven of the patients were being treated with infliximab, four were being treated with adalimumab, and one was being treated with certolizumab. All stopped anti-TNF therapy once they were diagnosed with tuberculosis.

Dr. Guinard and associates noted that the low sensitivity of Mycobacterium tuberculosis diagnostic tests was “a striking feature” of these cases. Only one-third of the patients showed a positive direct Ziehl-Neelsen stain for acid-fast bacilli and half had a positive culture.

“According to this study and published experience, in a patient with suggestive symptoms, a negative Mycobacterium tuberculosis test should not delay the decision to initiate anti-tuberculosis treatment,” they wrote. “This is particularly important considering the high mortality of tuberculosis in patients treated with TNF antagonists,” which ranges from 6%-17%, they added.

Two of the twelve patients – aged 77 and 32 years – died of disseminated tuberculosis disease during treatment for TB.

“This is the largest study of tuberculosis in psoriasis patients treated with TNF antagonists,” according to the authors.

No conflicts of interest were declared, and the study had no funding source.

Despite following guidelines aimed at reducing the likelihood of tuberculosis infection in patients with psoriasis treated with tumor necrosis factor antagonists, a French study has identified a number of active TB cases in this patient group.

The nationwide retrospective study identified 12 cases of tuberculosis in individuals with psoriasis during treatment with a TNF-antagonist between 2006 and 2014 – 9 men and 3 women, whose mean age was 49 years – according to Dr. E. Guinard of the dermatology service, CHU Toulouse Larrey at Paul Sabatier University, Toulouse, France, and associates (J Eur Acad Dermatol Venereol. 2016 Jun 3. doi: 10.1111/jdv.13633).

The investigators identified the cases from a national pharmacosurveillance database and by contacting members of the psoriasis research group in France’s national dermatology society and the national college of French dermatology professors.

Before starting anti-TNF therapy, all 12 patients had been screened for latent TB based on French guidelines: three patients were tested with the tuberculosis skin test alone, six were tested with QuantiFERON-TB Gold test, and three patients had both the skin test and QuantiFERON-TB. Each had a pretreatment chest x-ray.

Based on this testing, three were diagnosed with latent TB and received chemoprophylaxis; the other nine patients tested negative.

Information on TB risk factors was not available for all 12 cases, but three people had had contact with someone with TB during treatment. Three of the individuals had traveled to or were born in areas where TB was endemic, and one patient had had a case of TB in the family in the year before starting anti-TNF therapy. Nine patients had a known history of BCG vaccination, the investigators said.

The time between starting anti-TNF therapy and the appearance of TB symptoms ranged from 2 to 176 weeks (mean, 23 weeks), and diagnosis was based on clinical signs – such as fever, night sweats, and cough – and on imaging and laboratory investigations. Most (10) of the cases were extrapulmonary presentations, and two were pleuropulmonary. When diagnosed with tuberculosis, seven of the patients were being treated with infliximab, four were being treated with adalimumab, and one was being treated with certolizumab. All stopped anti-TNF therapy once they were diagnosed with tuberculosis.

Dr. Guinard and associates noted that the low sensitivity of Mycobacterium tuberculosis diagnostic tests was “a striking feature” of these cases. Only one-third of the patients showed a positive direct Ziehl-Neelsen stain for acid-fast bacilli and half had a positive culture.

“According to this study and published experience, in a patient with suggestive symptoms, a negative Mycobacterium tuberculosis test should not delay the decision to initiate anti-tuberculosis treatment,” they wrote. “This is particularly important considering the high mortality of tuberculosis in patients treated with TNF antagonists,” which ranges from 6%-17%, they added.

Two of the twelve patients – aged 77 and 32 years – died of disseminated tuberculosis disease during treatment for TB.

“This is the largest study of tuberculosis in psoriasis patients treated with TNF antagonists,” according to the authors.

No conflicts of interest were declared, and the study had no funding source.

Despite following guidelines aimed at reducing the likelihood of tuberculosis infection in patients with psoriasis treated with tumor necrosis factor antagonists, a French study has identified a number of active TB cases in this patient group.

The nationwide retrospective study identified 12 cases of tuberculosis in individuals with psoriasis during treatment with a TNF-antagonist between 2006 and 2014 – 9 men and 3 women, whose mean age was 49 years – according to Dr. E. Guinard of the dermatology service, CHU Toulouse Larrey at Paul Sabatier University, Toulouse, France, and associates (J Eur Acad Dermatol Venereol. 2016 Jun 3. doi: 10.1111/jdv.13633).

The investigators identified the cases from a national pharmacosurveillance database and by contacting members of the psoriasis research group in France’s national dermatology society and the national college of French dermatology professors.

Before starting anti-TNF therapy, all 12 patients had been screened for latent TB based on French guidelines: three patients were tested with the tuberculosis skin test alone, six were tested with QuantiFERON-TB Gold test, and three patients had both the skin test and QuantiFERON-TB. Each had a pretreatment chest x-ray.

Based on this testing, three were diagnosed with latent TB and received chemoprophylaxis; the other nine patients tested negative.

Information on TB risk factors was not available for all 12 cases, but three people had had contact with someone with TB during treatment. Three of the individuals had traveled to or were born in areas where TB was endemic, and one patient had had a case of TB in the family in the year before starting anti-TNF therapy. Nine patients had a known history of BCG vaccination, the investigators said.

The time between starting anti-TNF therapy and the appearance of TB symptoms ranged from 2 to 176 weeks (mean, 23 weeks), and diagnosis was based on clinical signs – such as fever, night sweats, and cough – and on imaging and laboratory investigations. Most (10) of the cases were extrapulmonary presentations, and two were pleuropulmonary. When diagnosed with tuberculosis, seven of the patients were being treated with infliximab, four were being treated with adalimumab, and one was being treated with certolizumab. All stopped anti-TNF therapy once they were diagnosed with tuberculosis.

Dr. Guinard and associates noted that the low sensitivity of Mycobacterium tuberculosis diagnostic tests was “a striking feature” of these cases. Only one-third of the patients showed a positive direct Ziehl-Neelsen stain for acid-fast bacilli and half had a positive culture.

“According to this study and published experience, in a patient with suggestive symptoms, a negative Mycobacterium tuberculosis test should not delay the decision to initiate anti-tuberculosis treatment,” they wrote. “This is particularly important considering the high mortality of tuberculosis in patients treated with TNF antagonists,” which ranges from 6%-17%, they added.

Two of the twelve patients – aged 77 and 32 years – died of disseminated tuberculosis disease during treatment for TB.

“This is the largest study of tuberculosis in psoriasis patients treated with TNF antagonists,” according to the authors.

No conflicts of interest were declared, and the study had no funding source.

Rheumatoid arthritis patients on anti–tumor necrosis factor medications had approximately twice the rate of serious adverse events as did psoriasis patients on the same medications, based on data from a pair of prospective studies of about 4,000 adults.

The findings were published online in the British Journal of Dermatology.

“Current trends are to extrapolate the abundant literature existing on the safety of TNF antagonists in RA to define safety management for psoriasis,” wrote Dr. Ignacio García-Doval of the Fundación Academia Española de Dermatología y Venereología, Madrid, and colleagues. However, data on the similarity of risk associated with anti-TNF medications in RA and psoriasis are limited, the investigators said (BJD. 2016. doi: 10.1111/bjd.14776).

The researchers compared data from two similarly designed, overlapping prospective safety registry studies of anti-TNF medications in RA patients (the BIOBADASER study) and psoriasis patients (the BIOBADADERM study).

In the cohort of 3,171 RA patients, the researchers identified 1,248 serious or fatal adverse events during 16,230 person-years of follow-up; in the cohort of 946 psoriasis patients, they identified 124 serious or fatal adverse events during 2,760 person-years of follow-up. The resulting incidence rate ratio of psoriasis to RA was 0.6. The increased risk of serious adverse events for RA patients compared with psoriasis patients remained after the investigators controlled for confounding factors including age, sex, treatments, and comorbid conditions including hypertension, diabetes, hypercholesterolemia, and methotrexate therapy, for a hazard ratio of 0.54.

Moreover, the types of serious adverse events were different between the RA and psoriasis groups. Among those with RA, the rates of serious infections, cardiac disorders, respiratory disorders, and infusion reactions were significantly greater among those with RA, while psoriatic patients “had more skin and subcutaneous tissue disorders and hepatobiliary disorders,” the researchers noted.

By contrast, “rates of nonserious adverse events cannot be compared between the two cohorts,” because of differences in definitions, they pointed out. These differences resulted in a nonserious adverse event rate that was more than twice as high in the psoriasis group as in the RA group (582.2 events per 1,000 patient-years vs. 242.8 events per 1,000 patient-years).

Based on the findings, “published safety results of TNF-antagonists in RA cannot be fully extrapolated to psoriasis, as patients with RA have a higher risk and a different pattern of serious adverse events,” they concluded.

The BIOBADADERM project is promoted by the Fundación Academia Española de Dermatología y Venereología, which is supported by the Spanish Medicines and Health Products Agency and by multiple pharmaceutical companies. BIOBADASER received funding from Fundacion Española de Reumatología and the Spanish Medicines and Health Products Agency and grants from numerous pharmaceutical companies. Lead author Dr. Garcia-Doval disclosed travel grants for congresses from Merck/Schering-Plough Pharmaceuticals, Pfizer, and Janssen; the remaining two authors disclosed being a speaker and/or a consultant for several companies, including AbbVie.

Rheumatoid arthritis patients on anti–tumor necrosis factor medications had approximately twice the rate of serious adverse events as did psoriasis patients on the same medications, based on data from a pair of prospective studies of about 4,000 adults.

The findings were published online in the British Journal of Dermatology.

“Current trends are to extrapolate the abundant literature existing on the safety of TNF antagonists in RA to define safety management for psoriasis,” wrote Dr. Ignacio García-Doval of the Fundación Academia Española de Dermatología y Venereología, Madrid, and colleagues. However, data on the similarity of risk associated with anti-TNF medications in RA and psoriasis are limited, the investigators said (BJD. 2016. doi: 10.1111/bjd.14776).

The researchers compared data from two similarly designed, overlapping prospective safety registry studies of anti-TNF medications in RA patients (the BIOBADASER study) and psoriasis patients (the BIOBADADERM study).

In the cohort of 3,171 RA patients, the researchers identified 1,248 serious or fatal adverse events during 16,230 person-years of follow-up; in the cohort of 946 psoriasis patients, they identified 124 serious or fatal adverse events during 2,760 person-years of follow-up. The resulting incidence rate ratio of psoriasis to RA was 0.6. The increased risk of serious adverse events for RA patients compared with psoriasis patients remained after the investigators controlled for confounding factors including age, sex, treatments, and comorbid conditions including hypertension, diabetes, hypercholesterolemia, and methotrexate therapy, for a hazard ratio of 0.54.

Moreover, the types of serious adverse events were different between the RA and psoriasis groups. Among those with RA, the rates of serious infections, cardiac disorders, respiratory disorders, and infusion reactions were significantly greater among those with RA, while psoriatic patients “had more skin and subcutaneous tissue disorders and hepatobiliary disorders,” the researchers noted.

By contrast, “rates of nonserious adverse events cannot be compared between the two cohorts,” because of differences in definitions, they pointed out. These differences resulted in a nonserious adverse event rate that was more than twice as high in the psoriasis group as in the RA group (582.2 events per 1,000 patient-years vs. 242.8 events per 1,000 patient-years).

Based on the findings, “published safety results of TNF-antagonists in RA cannot be fully extrapolated to psoriasis, as patients with RA have a higher risk and a different pattern of serious adverse events,” they concluded.

The BIOBADADERM project is promoted by the Fundación Academia Española de Dermatología y Venereología, which is supported by the Spanish Medicines and Health Products Agency and by multiple pharmaceutical companies. BIOBADASER received funding from Fundacion Española de Reumatología and the Spanish Medicines and Health Products Agency and grants from numerous pharmaceutical companies. Lead author Dr. Garcia-Doval disclosed travel grants for congresses from Merck/Schering-Plough Pharmaceuticals, Pfizer, and Janssen; the remaining two authors disclosed being a speaker and/or a consultant for several companies, including AbbVie.

Rheumatoid arthritis patients on anti–tumor necrosis factor medications had approximately twice the rate of serious adverse events as did psoriasis patients on the same medications, based on data from a pair of prospective studies of about 4,000 adults.

The findings were published online in the British Journal of Dermatology.

“Current trends are to extrapolate the abundant literature existing on the safety of TNF antagonists in RA to define safety management for psoriasis,” wrote Dr. Ignacio García-Doval of the Fundación Academia Española de Dermatología y Venereología, Madrid, and colleagues. However, data on the similarity of risk associated with anti-TNF medications in RA and psoriasis are limited, the investigators said (BJD. 2016. doi: 10.1111/bjd.14776).

The researchers compared data from two similarly designed, overlapping prospective safety registry studies of anti-TNF medications in RA patients (the BIOBADASER study) and psoriasis patients (the BIOBADADERM study).

In the cohort of 3,171 RA patients, the researchers identified 1,248 serious or fatal adverse events during 16,230 person-years of follow-up; in the cohort of 946 psoriasis patients, they identified 124 serious or fatal adverse events during 2,760 person-years of follow-up. The resulting incidence rate ratio of psoriasis to RA was 0.6. The increased risk of serious adverse events for RA patients compared with psoriasis patients remained after the investigators controlled for confounding factors including age, sex, treatments, and comorbid conditions including hypertension, diabetes, hypercholesterolemia, and methotrexate therapy, for a hazard ratio of 0.54.

Moreover, the types of serious adverse events were different between the RA and psoriasis groups. Among those with RA, the rates of serious infections, cardiac disorders, respiratory disorders, and infusion reactions were significantly greater among those with RA, while psoriatic patients “had more skin and subcutaneous tissue disorders and hepatobiliary disorders,” the researchers noted.

By contrast, “rates of nonserious adverse events cannot be compared between the two cohorts,” because of differences in definitions, they pointed out. These differences resulted in a nonserious adverse event rate that was more than twice as high in the psoriasis group as in the RA group (582.2 events per 1,000 patient-years vs. 242.8 events per 1,000 patient-years).

Based on the findings, “published safety results of TNF-antagonists in RA cannot be fully extrapolated to psoriasis, as patients with RA have a higher risk and a different pattern of serious adverse events,” they concluded.

The BIOBADADERM project is promoted by the Fundación Academia Española de Dermatología y Venereología, which is supported by the Spanish Medicines and Health Products Agency and by multiple pharmaceutical companies. BIOBADASER received funding from Fundacion Española de Reumatología and the Spanish Medicines and Health Products Agency and grants from numerous pharmaceutical companies. Lead author Dr. Garcia-Doval disclosed travel grants for congresses from Merck/Schering-Plough Pharmaceuticals, Pfizer, and Janssen; the remaining two authors disclosed being a speaker and/or a consultant for several companies, including AbbVie.

More than half of the patients treated with the interleukin-17A antagonist, ixekizumab, achieved full resolution of skin plaques after a year of 2- to 4-week dosing, according to the latest analysis of data from the three UNCOVER trials of almost 4,000 patients with moderate to severe psoriasis.

The results of the three randomized, double-blind placebo-controlled pivotal trials were published online in the New England Journal of Medicine (doi: 10.1056/NEJMoa1512711).

Ixekizumab was approved in March for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy; it is marketed as Taltz by Eli Lilly. Some of the UNCOVER data have been previously reported. The UNCOVER studies were conducted at more than 100 sites in 21 countries.

Patients in the UNCOVER trials were randomized to 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg, 80 mg every 4 weeks after the same starting dose, or subcutaneous placebo injections, for 12 weeks.

In the UNCOVER-2 and UNCOVER-3 trials, additional cohorts were also randomized to twice-weekly etanercept (50 mg). All three trials also included a long-term extension period to 60 weeks, which was randomly assigned in UNCOVER-3 (where patients received 80 mg of ixekizumab every 4 weeks), or was implemented for all patients who responded to ixekizumab in the other two trials (where patients were randomized to 80 mg every 4 or 12 weeks, or placebo).

In the UNCOVER-1 trial in 1,296 patients, 89.1% of patients in the 2-week dosing group and 82.6% of the 4-week dosing group had achieved a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75) by week 12, compared with 3.9% in the placebo group (P less than .0001 for all). Similarly, 35.3% of patients in the 2-week dosing group and 33.6% of those in the 4-week dosing group achieved a PASI score of 100 by week 12.

The high response rates seen during the induction period “were generally maintained during the long-term extension period in UNCOVER-3,” wrote Dr. Kenneth B. Gordon, professor of dermatology, Northwestern University, Chicago, and his coauthors. In the analysis of the long-term data from UNCOVER-3, the researchers reported that by week 60, 55% of patients receiving 80 mg of ixekizumab every 2 weeks during the induction period had achieved a PASI 100, and 52% of patients receiving ixekizumab every 4 weeks during the induction period had achieved a PASI 100.

Patients randomized to 80 mg of ixekizumab every 12 weeks after the first 12 weeks of treatment also showed significant long-term responses in the UNCOVER-1 and -2 trials. Nearly half (49.1%) of those who were initiated on 2-week dosing and 44.9% of those initiated on 4-week dosing achieved a PASI score of 75 on the 12-week dosing schedule, compared with 8%-9% of those randomized to placebo from week 12 through week 60.

The authors concluded that ixekizumab “provided high levels of clinical response at week 12 and through week 60,” adding, however, that “as with any treatment, the benefits need to be weighed against the adverse events, and the safety profile of longer-term treatment with ixekizumab should be examined.”

Although low serum IL-17 levels have previously been linked with cardiovascular disease, the study found no significant differences between the treatment and placebo groups in adverse cardiovascular events. Candidal infections were more common among those treated with ixekizumab, “a finding that is consistent with the role of IL-17A in the mucocutaneous defense against fungal infections,” they wrote.

There were 11 cases of inflammatory bowel disease reported among patients during treatment with ixekizumab and another three cases in patients receiving placebo during a randomized withdrawal period, who had received ixekizumab during the induction* period. These results “suggest that further evaluation is needed to understand the relationship between IL-17A inhibitors and inflammatory bowel disease,” the investigators said.

The authors of the study include Eli Lilly employees, several of whom also have stock options; the other authors declared a range of funding, advisory board positions, and speakers fees from pharmaceutical companies, including Eli Lilly. The UNCOVER studies were sponsored by Eli Lilly.

*A previous version of this article misstated the period during which three placebo patients received ixekizumab.

More than half of the patients treated with the interleukin-17A antagonist, ixekizumab, achieved full resolution of skin plaques after a year of 2- to 4-week dosing, according to the latest analysis of data from the three UNCOVER trials of almost 4,000 patients with moderate to severe psoriasis.

The results of the three randomized, double-blind placebo-controlled pivotal trials were published online in the New England Journal of Medicine (doi: 10.1056/NEJMoa1512711).

Ixekizumab was approved in March for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy; it is marketed as Taltz by Eli Lilly. Some of the UNCOVER data have been previously reported. The UNCOVER studies were conducted at more than 100 sites in 21 countries.

Patients in the UNCOVER trials were randomized to 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg, 80 mg every 4 weeks after the same starting dose, or subcutaneous placebo injections, for 12 weeks.

In the UNCOVER-2 and UNCOVER-3 trials, additional cohorts were also randomized to twice-weekly etanercept (50 mg). All three trials also included a long-term extension period to 60 weeks, which was randomly assigned in UNCOVER-3 (where patients received 80 mg of ixekizumab every 4 weeks), or was implemented for all patients who responded to ixekizumab in the other two trials (where patients were randomized to 80 mg every 4 or 12 weeks, or placebo).

In the UNCOVER-1 trial in 1,296 patients, 89.1% of patients in the 2-week dosing group and 82.6% of the 4-week dosing group had achieved a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75) by week 12, compared with 3.9% in the placebo group (P less than .0001 for all). Similarly, 35.3% of patients in the 2-week dosing group and 33.6% of those in the 4-week dosing group achieved a PASI score of 100 by week 12.

The high response rates seen during the induction period “were generally maintained during the long-term extension period in UNCOVER-3,” wrote Dr. Kenneth B. Gordon, professor of dermatology, Northwestern University, Chicago, and his coauthors. In the analysis of the long-term data from UNCOVER-3, the researchers reported that by week 60, 55% of patients receiving 80 mg of ixekizumab every 2 weeks during the induction period had achieved a PASI 100, and 52% of patients receiving ixekizumab every 4 weeks during the induction period had achieved a PASI 100.

Patients randomized to 80 mg of ixekizumab every 12 weeks after the first 12 weeks of treatment also showed significant long-term responses in the UNCOVER-1 and -2 trials. Nearly half (49.1%) of those who were initiated on 2-week dosing and 44.9% of those initiated on 4-week dosing achieved a PASI score of 75 on the 12-week dosing schedule, compared with 8%-9% of those randomized to placebo from week 12 through week 60.

The authors concluded that ixekizumab “provided high levels of clinical response at week 12 and through week 60,” adding, however, that “as with any treatment, the benefits need to be weighed against the adverse events, and the safety profile of longer-term treatment with ixekizumab should be examined.”

Although low serum IL-17 levels have previously been linked with cardiovascular disease, the study found no significant differences between the treatment and placebo groups in adverse cardiovascular events. Candidal infections were more common among those treated with ixekizumab, “a finding that is consistent with the role of IL-17A in the mucocutaneous defense against fungal infections,” they wrote.

There were 11 cases of inflammatory bowel disease reported among patients during treatment with ixekizumab and another three cases in patients receiving placebo during a randomized withdrawal period, who had received ixekizumab during the induction* period. These results “suggest that further evaluation is needed to understand the relationship between IL-17A inhibitors and inflammatory bowel disease,” the investigators said.

The authors of the study include Eli Lilly employees, several of whom also have stock options; the other authors declared a range of funding, advisory board positions, and speakers fees from pharmaceutical companies, including Eli Lilly. The UNCOVER studies were sponsored by Eli Lilly.

*A previous version of this article misstated the period during which three placebo patients received ixekizumab.

More than half of the patients treated with the interleukin-17A antagonist, ixekizumab, achieved full resolution of skin plaques after a year of 2- to 4-week dosing, according to the latest analysis of data from the three UNCOVER trials of almost 4,000 patients with moderate to severe psoriasis.

The results of the three randomized, double-blind placebo-controlled pivotal trials were published online in the New England Journal of Medicine (doi: 10.1056/NEJMoa1512711).

Ixekizumab was approved in March for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy; it is marketed as Taltz by Eli Lilly. Some of the UNCOVER data have been previously reported. The UNCOVER studies were conducted at more than 100 sites in 21 countries.

Patients in the UNCOVER trials were randomized to 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg, 80 mg every 4 weeks after the same starting dose, or subcutaneous placebo injections, for 12 weeks.

In the UNCOVER-2 and UNCOVER-3 trials, additional cohorts were also randomized to twice-weekly etanercept (50 mg). All three trials also included a long-term extension period to 60 weeks, which was randomly assigned in UNCOVER-3 (where patients received 80 mg of ixekizumab every 4 weeks), or was implemented for all patients who responded to ixekizumab in the other two trials (where patients were randomized to 80 mg every 4 or 12 weeks, or placebo).

In the UNCOVER-1 trial in 1,296 patients, 89.1% of patients in the 2-week dosing group and 82.6% of the 4-week dosing group had achieved a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75) by week 12, compared with 3.9% in the placebo group (P less than .0001 for all). Similarly, 35.3% of patients in the 2-week dosing group and 33.6% of those in the 4-week dosing group achieved a PASI score of 100 by week 12.

The high response rates seen during the induction period “were generally maintained during the long-term extension period in UNCOVER-3,” wrote Dr. Kenneth B. Gordon, professor of dermatology, Northwestern University, Chicago, and his coauthors. In the analysis of the long-term data from UNCOVER-3, the researchers reported that by week 60, 55% of patients receiving 80 mg of ixekizumab every 2 weeks during the induction period had achieved a PASI 100, and 52% of patients receiving ixekizumab every 4 weeks during the induction period had achieved a PASI 100.

Patients randomized to 80 mg of ixekizumab every 12 weeks after the first 12 weeks of treatment also showed significant long-term responses in the UNCOVER-1 and -2 trials. Nearly half (49.1%) of those who were initiated on 2-week dosing and 44.9% of those initiated on 4-week dosing achieved a PASI score of 75 on the 12-week dosing schedule, compared with 8%-9% of those randomized to placebo from week 12 through week 60.

The authors concluded that ixekizumab “provided high levels of clinical response at week 12 and through week 60,” adding, however, that “as with any treatment, the benefits need to be weighed against the adverse events, and the safety profile of longer-term treatment with ixekizumab should be examined.”

Although low serum IL-17 levels have previously been linked with cardiovascular disease, the study found no significant differences between the treatment and placebo groups in adverse cardiovascular events. Candidal infections were more common among those treated with ixekizumab, “a finding that is consistent with the role of IL-17A in the mucocutaneous defense against fungal infections,” they wrote.

There were 11 cases of inflammatory bowel disease reported among patients during treatment with ixekizumab and another three cases in patients receiving placebo during a randomized withdrawal period, who had received ixekizumab during the induction* period. These results “suggest that further evaluation is needed to understand the relationship between IL-17A inhibitors and inflammatory bowel disease,” the investigators said.

The authors of the study include Eli Lilly employees, several of whom also have stock options; the other authors declared a range of funding, advisory board positions, and speakers fees from pharmaceutical companies, including Eli Lilly. The UNCOVER studies were sponsored by Eli Lilly.

*A previous version of this article misstated the period during which three placebo patients received ixekizumab.

In a study published online on April 14 in Arteriosclerosis, Thrombosis, and Vascular Biology, Khalid et al evaluated the risk for AAA in patients with psoriasis in a nationwide cohort study in Denmark. The study participants were Danish residents 18 years and older who were observed from January 1, 1997 until diagnosis of AAA; December 31, 2011; migration; or death. Incidence rates for AAA were calculated, and incidence rate ratios were adjusted for age, sex, comorbidity, medications, socioeconomic status, and smoking.

A total of 5,495,203 individuals were eligible for this study. Of them, Khalid et al identified 59,423 patients with mild psoriasis and 11,566 patients with severe psoriasis. The overall incidence rates of AAA were 3.72, 7.30, and 9.87 per 10,000 person-years for the reference population (23,696 cases), mild psoriasis (240 cases), and severe psoriasis (50 cases), respectively. The corresponding adjusted incidence rate ratios for AAA were increased in patients with psoriasis with incidence rate ratios of 1.20 (95% CI, 1.03-1.39) and 1.67 (95% CI, 1.21-2.32) for individuals with mild and severe disease, respectively.

Khalid et al concluded that psoriasis was associated with a disease severity–dependent increased risk for AAA; however, the mechanisms and consequences of this novel finding require further investigation.

What’s the issue?

Another example of an association of a comorbidity with psoriasis, this finding emphasizes the need for cardiovascular referral in psoriasis patients with risk factors such as hypertension and diabetes mellitus. How will these data influence your evaluation of psoriasis patients?

We want to know your views! Tell us what you think.

In a study published online on April 14 in Arteriosclerosis, Thrombosis, and Vascular Biology, Khalid et al evaluated the risk for AAA in patients with psoriasis in a nationwide cohort study in Denmark. The study participants were Danish residents 18 years and older who were observed from January 1, 1997 until diagnosis of AAA; December 31, 2011; migration; or death. Incidence rates for AAA were calculated, and incidence rate ratios were adjusted for age, sex, comorbidity, medications, socioeconomic status, and smoking.

A total of 5,495,203 individuals were eligible for this study. Of them, Khalid et al identified 59,423 patients with mild psoriasis and 11,566 patients with severe psoriasis. The overall incidence rates of AAA were 3.72, 7.30, and 9.87 per 10,000 person-years for the reference population (23,696 cases), mild psoriasis (240 cases), and severe psoriasis (50 cases), respectively. The corresponding adjusted incidence rate ratios for AAA were increased in patients with psoriasis with incidence rate ratios of 1.20 (95% CI, 1.03-1.39) and 1.67 (95% CI, 1.21-2.32) for individuals with mild and severe disease, respectively.

Khalid et al concluded that psoriasis was associated with a disease severity–dependent increased risk for AAA; however, the mechanisms and consequences of this novel finding require further investigation.

What’s the issue?

Another example of an association of a comorbidity with psoriasis, this finding emphasizes the need for cardiovascular referral in psoriasis patients with risk factors such as hypertension and diabetes mellitus. How will these data influence your evaluation of psoriasis patients?

We want to know your views! Tell us what you think.

In a study published online on April 14 in Arteriosclerosis, Thrombosis, and Vascular Biology, Khalid et al evaluated the risk for AAA in patients with psoriasis in a nationwide cohort study in Denmark. The study participants were Danish residents 18 years and older who were observed from January 1, 1997 until diagnosis of AAA; December 31, 2011; migration; or death. Incidence rates for AAA were calculated, and incidence rate ratios were adjusted for age, sex, comorbidity, medications, socioeconomic status, and smoking.

A total of 5,495,203 individuals were eligible for this study. Of them, Khalid et al identified 59,423 patients with mild psoriasis and 11,566 patients with severe psoriasis. The overall incidence rates of AAA were 3.72, 7.30, and 9.87 per 10,000 person-years for the reference population (23,696 cases), mild psoriasis (240 cases), and severe psoriasis (50 cases), respectively. The corresponding adjusted incidence rate ratios for AAA were increased in patients with psoriasis with incidence rate ratios of 1.20 (95% CI, 1.03-1.39) and 1.67 (95% CI, 1.21-2.32) for individuals with mild and severe disease, respectively.

Khalid et al concluded that psoriasis was associated with a disease severity–dependent increased risk for AAA; however, the mechanisms and consequences of this novel finding require further investigation.

What’s the issue?

Another example of an association of a comorbidity with psoriasis, this finding emphasizes the need for cardiovascular referral in psoriasis patients with risk factors such as hypertension and diabetes mellitus. How will these data influence your evaluation of psoriasis patients?

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SCOTTSDALE, ARIZ. – From enterocolitis to MRSA, serious infections are on the rise among inpatients with psoriasis, and psoriasis is an independent risk factor for serious infections, according to findings from large retrospective studies from the United States and the United Kingdom.

Inpatients with psoriasis in the United States also were at greater risk of serious infections, compared with nonpsoriatic inpatients at every time point studied, and serious infections were associated with increased hospital costs, length of stay, and risk of mortality, reported Derek Hsu, a medical student at Northwestern University, Chicago, and his associates. “Research is needed to determine how to reduce the risk of serious infections in patients with psoriasis,” the investigators emphasized.

©David Parr/ thinkstockphotos.com

Psoriasis affects some 7 million adults in the United States. Biologics, which are transforming the treatment landscape for moderate-to-severe psoriasis, “should reduce inherent infectious risk by controlling the inflammatory process and reducing disease severity, [but] these effects may be immunosuppressing and increase the risk of infection in other ways,” according to Mr. Hsu and his associates. For their study, they analyzed data for 2002-2012 from the Nationwide Inpatient Sample, which covers 20% of hospitalizations in the United States. They extracted validated ICD-9 codes for psoriasis and serious infections, and calculated costs of care after adjusting for 2014 inflation, based on the United States Consumer Price Index.

Overall rates of serious infection and rates of pneumonia, MRSA, septicemia, diverticulitis, enterocolitis, encephalitis, and any viral or fungal infection rose significantly among inpatients with psoriasis between 2002 and 2012 (all P-values less than .05). Predictors of serious infections among inpatients with psoriasis included diabetes mellitus, obesity, and being of non-Caucasian race or ethnicity, female, older than 60 years, and on Medicare or Medicaid, the researchers reported at the annual meeting of the Society for Investigative Dermatology.

Furthermore, after controlling for age, sex, and race, psoriasis was a significant risk factor for many different types of serious infections. Among these were cellulitis, herpes simplex virus, infectious arthritis, osteomyelitis, meningitis, influenza, encephalitis, septicemia, enterocolitis, MRSA, methicillin-sensitive Staphylococcus aureus infections, and Clostridium difficile. Further, inpatients with psoriasis were more prone to urinary tract infection, peritonitis or intestinal abscess, appendicitis, tuberculosis, and viral and fungal infections (all P-values less than .05). The average cost of hospital stay for inpatients with psoriasis was more than $2,200 greater when they were diagnosed with one or more serious infections than otherwise, and their average length of hospital stay was 2 days longer.

The study in the United Kingdom included nearly 200,000 patients with psoriasis and almost 1 million patients without psoriasis from The Health Improvement Network electronic medical record database. Between 2002 and 2013, patients without psoriasis developed an estimated 78.5 serious infections per 100,000 person-years, compared with 88.9, 85.7, and 145.7 serious infections per 100,000 person-years, respectively, for all psoriasis patients, patients with mild disease, and patients with severe disease requiring systemic or phototherapy, said Dr. Junko Takeshita and her colleagues at the University of Pennsylvania in Philadelphia. After controlling for many potential demographic and clinical confounders, psoriasis increased the risk of serious infection by about 21% (hazard ratio, 1.21; 95% confidence interval, 1.18-1.23). Patients with severe psoriasis had a 63% greater risk of infection than patients without psoriasis, compared with an 18% increase for patients with mild psoriasis.

The findings show “serious infection, particularly respiratory and skin or soft tissue infections, to be an important and common cause of morbidity among patients with psoriasis, especially those with more severe disease,” Dr. Takeshita and her associates said. Notably, the link between psoriasis and risk of serious infection persisted after excluding patients on immunosuppressive therapies, suggesting “that the greater infection risk is at least partially attributable to more severe psoriasis, itself,” they added.

The analysis of Nationwide Inpatient Sample data was funded by the Agency for Healthcare Research and Quality and by the Dermatology Foundation. The analysis of Health Improvement Network data was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, which is part of the National Institutes of Health, and by the Dermatology Foundation. None of the investigators reported conflicts of interest.

SCOTTSDALE, ARIZ. – From enterocolitis to MRSA, serious infections are on the rise among inpatients with psoriasis, and psoriasis is an independent risk factor for serious infections, according to findings from large retrospective studies from the United States and the United Kingdom.

Inpatients with psoriasis in the United States also were at greater risk of serious infections, compared with nonpsoriatic inpatients at every time point studied, and serious infections were associated with increased hospital costs, length of stay, and risk of mortality, reported Derek Hsu, a medical student at Northwestern University, Chicago, and his associates. “Research is needed to determine how to reduce the risk of serious infections in patients with psoriasis,” the investigators emphasized.

©David Parr/ thinkstockphotos.com

Psoriasis affects some 7 million adults in the United States. Biologics, which are transforming the treatment landscape for moderate-to-severe psoriasis, “should reduce inherent infectious risk by controlling the inflammatory process and reducing disease severity, [but] these effects may be immunosuppressing and increase the risk of infection in other ways,” according to Mr. Hsu and his associates. For their study, they analyzed data for 2002-2012 from the Nationwide Inpatient Sample, which covers 20% of hospitalizations in the United States. They extracted validated ICD-9 codes for psoriasis and serious infections, and calculated costs of care after adjusting for 2014 inflation, based on the United States Consumer Price Index.

Overall rates of serious infection and rates of pneumonia, MRSA, septicemia, diverticulitis, enterocolitis, encephalitis, and any viral or fungal infection rose significantly among inpatients with psoriasis between 2002 and 2012 (all P-values less than .05). Predictors of serious infections among inpatients with psoriasis included diabetes mellitus, obesity, and being of non-Caucasian race or ethnicity, female, older than 60 years, and on Medicare or Medicaid, the researchers reported at the annual meeting of the Society for Investigative Dermatology.

Furthermore, after controlling for age, sex, and race, psoriasis was a significant risk factor for many different types of serious infections. Among these were cellulitis, herpes simplex virus, infectious arthritis, osteomyelitis, meningitis, influenza, encephalitis, septicemia, enterocolitis, MRSA, methicillin-sensitive Staphylococcus aureus infections, and Clostridium difficile. Further, inpatients with psoriasis were more prone to urinary tract infection, peritonitis or intestinal abscess, appendicitis, tuberculosis, and viral and fungal infections (all P-values less than .05). The average cost of hospital stay for inpatients with psoriasis was more than $2,200 greater when they were diagnosed with one or more serious infections than otherwise, and their average length of hospital stay was 2 days longer.

The study in the United Kingdom included nearly 200,000 patients with psoriasis and almost 1 million patients without psoriasis from The Health Improvement Network electronic medical record database. Between 2002 and 2013, patients without psoriasis developed an estimated 78.5 serious infections per 100,000 person-years, compared with 88.9, 85.7, and 145.7 serious infections per 100,000 person-years, respectively, for all psoriasis patients, patients with mild disease, and patients with severe disease requiring systemic or phototherapy, said Dr. Junko Takeshita and her colleagues at the University of Pennsylvania in Philadelphia. After controlling for many potential demographic and clinical confounders, psoriasis increased the risk of serious infection by about 21% (hazard ratio, 1.21; 95% confidence interval, 1.18-1.23). Patients with severe psoriasis had a 63% greater risk of infection than patients without psoriasis, compared with an 18% increase for patients with mild psoriasis.

The findings show “serious infection, particularly respiratory and skin or soft tissue infections, to be an important and common cause of morbidity among patients with psoriasis, especially those with more severe disease,” Dr. Takeshita and her associates said. Notably, the link between psoriasis and risk of serious infection persisted after excluding patients on immunosuppressive therapies, suggesting “that the greater infection risk is at least partially attributable to more severe psoriasis, itself,” they added.

The analysis of Nationwide Inpatient Sample data was funded by the Agency for Healthcare Research and Quality and by the Dermatology Foundation. The analysis of Health Improvement Network data was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, which is part of the National Institutes of Health, and by the Dermatology Foundation. None of the investigators reported conflicts of interest.

SCOTTSDALE, ARIZ. – From enterocolitis to MRSA, serious infections are on the rise among inpatients with psoriasis, and psoriasis is an independent risk factor for serious infections, according to findings from large retrospective studies from the United States and the United Kingdom.

Inpatients with psoriasis in the United States also were at greater risk of serious infections, compared with nonpsoriatic inpatients at every time point studied, and serious infections were associated with increased hospital costs, length of stay, and risk of mortality, reported Derek Hsu, a medical student at Northwestern University, Chicago, and his associates. “Research is needed to determine how to reduce the risk of serious infections in patients with psoriasis,” the investigators emphasized.

©David Parr/ thinkstockphotos.com

Psoriasis affects some 7 million adults in the United States. Biologics, which are transforming the treatment landscape for moderate-to-severe psoriasis, “should reduce inherent infectious risk by controlling the inflammatory process and reducing disease severity, [but] these effects may be immunosuppressing and increase the risk of infection in other ways,” according to Mr. Hsu and his associates. For their study, they analyzed data for 2002-2012 from the Nationwide Inpatient Sample, which covers 20% of hospitalizations in the United States. They extracted validated ICD-9 codes for psoriasis and serious infections, and calculated costs of care after adjusting for 2014 inflation, based on the United States Consumer Price Index.

Overall rates of serious infection and rates of pneumonia, MRSA, septicemia, diverticulitis, enterocolitis, encephalitis, and any viral or fungal infection rose significantly among inpatients with psoriasis between 2002 and 2012 (all P-values less than .05). Predictors of serious infections among inpatients with psoriasis included diabetes mellitus, obesity, and being of non-Caucasian race or ethnicity, female, older than 60 years, and on Medicare or Medicaid, the researchers reported at the annual meeting of the Society for Investigative Dermatology.

Furthermore, after controlling for age, sex, and race, psoriasis was a significant risk factor for many different types of serious infections. Among these were cellulitis, herpes simplex virus, infectious arthritis, osteomyelitis, meningitis, influenza, encephalitis, septicemia, enterocolitis, MRSA, methicillin-sensitive Staphylococcus aureus infections, and Clostridium difficile. Further, inpatients with psoriasis were more prone to urinary tract infection, peritonitis or intestinal abscess, appendicitis, tuberculosis, and viral and fungal infections (all P-values less than .05). The average cost of hospital stay for inpatients with psoriasis was more than $2,200 greater when they were diagnosed with one or more serious infections than otherwise, and their average length of hospital stay was 2 days longer.

The study in the United Kingdom included nearly 200,000 patients with psoriasis and almost 1 million patients without psoriasis from The Health Improvement Network electronic medical record database. Between 2002 and 2013, patients without psoriasis developed an estimated 78.5 serious infections per 100,000 person-years, compared with 88.9, 85.7, and 145.7 serious infections per 100,000 person-years, respectively, for all psoriasis patients, patients with mild disease, and patients with severe disease requiring systemic or phototherapy, said Dr. Junko Takeshita and her colleagues at the University of Pennsylvania in Philadelphia. After controlling for many potential demographic and clinical confounders, psoriasis increased the risk of serious infection by about 21% (hazard ratio, 1.21; 95% confidence interval, 1.18-1.23). Patients with severe psoriasis had a 63% greater risk of infection than patients without psoriasis, compared with an 18% increase for patients with mild psoriasis.

The findings show “serious infection, particularly respiratory and skin or soft tissue infections, to be an important and common cause of morbidity among patients with psoriasis, especially those with more severe disease,” Dr. Takeshita and her associates said. Notably, the link between psoriasis and risk of serious infection persisted after excluding patients on immunosuppressive therapies, suggesting “that the greater infection risk is at least partially attributable to more severe psoriasis, itself,” they added.

The analysis of Nationwide Inpatient Sample data was funded by the Agency for Healthcare Research and Quality and by the Dermatology Foundation. The analysis of Health Improvement Network data was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, which is part of the National Institutes of Health, and by the Dermatology Foundation. None of the investigators reported conflicts of interest.

In recent years federal laws have been enacted to help provide more treatment options and possibly lower costs to patients for therapeutic biological products. You have likely heard or read about “biosimilars” on the U.S. drug market. But are you ready to make informed treatment decisions and answer patients’ questions about these new drugs?

Biosimilars are not “generic biologics.” Although the shared goal of making biosimilars and generic drugs available is to provide more treatment options, there are important differences between the two approval pathways. For instance, unlike generic drugs, which are “bioequivalent” to their reference listed drug, biosimilar products can be either “biosimilar” to or “interchangeable” with their reference product. The differences may seem subtle based on the terminology, but the differences are important, and health care professionals who prescribe, dispense, or administer these products will need to understand them – as well as other aspects of these new therapies.

To help busy health care professionals better understand biosimilar and interchangeable products, the FDA has created a free 1.5-hour continuing education program titled, FDA Overview of Biosimilar Products. The course describes the important characteristics of biological products, particularly their complexity. For instance, a single molecule of a biological product, such as a monoclonal antibody, can easily be many hundreds of times larger and much more complex than that of a “small molecule” drug such as aspirin. Their increased complexity is one reason they are regulated differently than generics – and why, in the case of biosimilars, the law allows some differences from the reference product in clinically inactive components. The CE course discusses the “inherent variability” in the production of all biological products – both reference and biosimilar – and how the FDA accounts for these differences in assessing safety and efficacy of the products. The course also provides detailed definitions of important terms – such as “biosimilar” and “interchangeable” – and an overview of the standards the FDA has established for reviewing and approving biosimilar and interchangeable products. It also outlines the FDA review and approval standards for biosimilars and interchangeable products to help practitioners be assured that these products have been demonstrated to be safe and effective treatment options for their patients.

Some of our most important and expensive drugs are biological products used to treat patients who have serious medical conditions that are often life threatening and usually life altering. In April 2016, the Food and Drug Administration approved Inflectra (infliximab-dyyb) to help treat certain patients with certain gastrointestinal disorders, such as Crohn’s disease, and for other indications such as treatment of psoriasis and rheumatoid arthritis. The product is approved but not yet marketed in the United States. However, last year, Zarxio (filgrastim-sndz) became the first biosimilar actually available in the U.S. marketplace – approved to help boost white blood cell production for patients with severe neutropenia as well as for patients receiving various cancer therapies. These products are “biosimilar” to already-approved biological products called “reference products.” Inflectra is biosimilar to the reference product, Remicade (infliximab), and Zarxio is biosimilar to Neupogen (filgrastim).

Use of safe and effective biosimilar and interchangeable biological products can potentially make treatment more affordable for patients in need and improve public health. As patients begin to ask about the use of biosimilar and interchangeable products, the FDA hopes this course will help prepare health care practitioners to make informed decisions on behalf of their patients.

Dr. Christl is Associate Director for Therapeutic Biologics at the Office of New Drugs, Center for Drug Evaluation and Research, FDA.

In recent years federal laws have been enacted to help provide more treatment options and possibly lower costs to patients for therapeutic biological products. You have likely heard or read about “biosimilars” on the U.S. drug market. But are you ready to make informed treatment decisions and answer patients’ questions about these new drugs?

Biosimilars are not “generic biologics.” Although the shared goal of making biosimilars and generic drugs available is to provide more treatment options, there are important differences between the two approval pathways. For instance, unlike generic drugs, which are “bioequivalent” to their reference listed drug, biosimilar products can be either “biosimilar” to or “interchangeable” with their reference product. The differences may seem subtle based on the terminology, but the differences are important, and health care professionals who prescribe, dispense, or administer these products will need to understand them – as well as other aspects of these new therapies.

To help busy health care professionals better understand biosimilar and interchangeable products, the FDA has created a free 1.5-hour continuing education program titled, FDA Overview of Biosimilar Products. The course describes the important characteristics of biological products, particularly their complexity. For instance, a single molecule of a biological product, such as a monoclonal antibody, can easily be many hundreds of times larger and much more complex than that of a “small molecule” drug such as aspirin. Their increased complexity is one reason they are regulated differently than generics – and why, in the case of biosimilars, the law allows some differences from the reference product in clinically inactive components. The CE course discusses the “inherent variability” in the production of all biological products – both reference and biosimilar – and how the FDA accounts for these differences in assessing safety and efficacy of the products. The course also provides detailed definitions of important terms – such as “biosimilar” and “interchangeable” – and an overview of the standards the FDA has established for reviewing and approving biosimilar and interchangeable products. It also outlines the FDA review and approval standards for biosimilars and interchangeable products to help practitioners be assured that these products have been demonstrated to be safe and effective treatment options for their patients.

Some of our most important and expensive drugs are biological products used to treat patients who have serious medical conditions that are often life threatening and usually life altering. In April 2016, the Food and Drug Administration approved Inflectra (infliximab-dyyb) to help treat certain patients with certain gastrointestinal disorders, such as Crohn’s disease, and for other indications such as treatment of psoriasis and rheumatoid arthritis. The product is approved but not yet marketed in the United States. However, last year, Zarxio (filgrastim-sndz) became the first biosimilar actually available in the U.S. marketplace – approved to help boost white blood cell production for patients with severe neutropenia as well as for patients receiving various cancer therapies. These products are “biosimilar” to already-approved biological products called “reference products.” Inflectra is biosimilar to the reference product, Remicade (infliximab), and Zarxio is biosimilar to Neupogen (filgrastim).

Use of safe and effective biosimilar and interchangeable biological products can potentially make treatment more affordable for patients in need and improve public health. As patients begin to ask about the use of biosimilar and interchangeable products, the FDA hopes this course will help prepare health care practitioners to make informed decisions on behalf of their patients.

Dr. Christl is Associate Director for Therapeutic Biologics at the Office of New Drugs, Center for Drug Evaluation and Research, FDA.

In recent years federal laws have been enacted to help provide more treatment options and possibly lower costs to patients for therapeutic biological products. You have likely heard or read about “biosimilars” on the U.S. drug market. But are you ready to make informed treatment decisions and answer patients’ questions about these new drugs?

Biosimilars are not “generic biologics.” Although the shared goal of making biosimilars and generic drugs available is to provide more treatment options, there are important differences between the two approval pathways. For instance, unlike generic drugs, which are “bioequivalent” to their reference listed drug, biosimilar products can be either “biosimilar” to or “interchangeable” with their reference product. The differences may seem subtle based on the terminology, but the differences are important, and health care professionals who prescribe, dispense, or administer these products will need to understand them – as well as other aspects of these new therapies.

To help busy health care professionals better understand biosimilar and interchangeable products, the FDA has created a free 1.5-hour continuing education program titled, FDA Overview of Biosimilar Products. The course describes the important characteristics of biological products, particularly their complexity. For instance, a single molecule of a biological product, such as a monoclonal antibody, can easily be many hundreds of times larger and much more complex than that of a “small molecule” drug such as aspirin. Their increased complexity is one reason they are regulated differently than generics – and why, in the case of biosimilars, the law allows some differences from the reference product in clinically inactive components. The CE course discusses the “inherent variability” in the production of all biological products – both reference and biosimilar – and how the FDA accounts for these differences in assessing safety and efficacy of the products. The course also provides detailed definitions of important terms – such as “biosimilar” and “interchangeable” – and an overview of the standards the FDA has established for reviewing and approving biosimilar and interchangeable products. It also outlines the FDA review and approval standards for biosimilars and interchangeable products to help practitioners be assured that these products have been demonstrated to be safe and effective treatment options for their patients.

Some of our most important and expensive drugs are biological products used to treat patients who have serious medical conditions that are often life threatening and usually life altering. In April 2016, the Food and Drug Administration approved Inflectra (infliximab-dyyb) to help treat certain patients with certain gastrointestinal disorders, such as Crohn’s disease, and for other indications such as treatment of psoriasis and rheumatoid arthritis. The product is approved but not yet marketed in the United States. However, last year, Zarxio (filgrastim-sndz) became the first biosimilar actually available in the U.S. marketplace – approved to help boost white blood cell production for patients with severe neutropenia as well as for patients receiving various cancer therapies. These products are “biosimilar” to already-approved biological products called “reference products.” Inflectra is biosimilar to the reference product, Remicade (infliximab), and Zarxio is biosimilar to Neupogen (filgrastim).

Use of safe and effective biosimilar and interchangeable biological products can potentially make treatment more affordable for patients in need and improve public health. As patients begin to ask about the use of biosimilar and interchangeable products, the FDA hopes this course will help prepare health care practitioners to make informed decisions on behalf of their patients.

Dr. Christl is Associate Director for Therapeutic Biologics at the Office of New Drugs, Center for Drug Evaluation and Research, FDA.

The investigational interleukin-17 inhibitor brodalumab was safe and effective in a small phase III Japanese study of adults with two rare and severe types of psoriasis, generalized pustular psoriasis (GPP) and psoriatic erythroderma (PsE). The results were published in the British Journal of Dermatology.

The 52-week open label studyevaluated the safety and efficacy of brodalumab in 30 Japanese adults (mean age 48 years) with GPP (12 patients) and PsE (18 patients). Brodalumab, a human monoclonal antibody against human IL-17RA that blocks the biologic activities of IL-17, was administered by subcutaneous injection. Efficacy was assessed via Clinical Global Impression of Improvement (CGI) scores, the primary endpoint (Br J Dermatol. 2016 April 23. doi: 10.1111/bjd.14702).

A high proportion of patients with either disease achieved “improved” or “remission” CGI scores at weeks 2, 12, and 52, reported Dr. Kenshi Yamasaki, of the department of dermatology at Tohoku University, Miyagi, Japan, and his associates

At week 52, almost 92% of those with GPP and 100% of those with PsE had achieved “improved” or “remission” scores. The most common adverse event was nasopharyngitis, which occurred in one-third of patients. Infection-related adverse events were grade 1 or 2, no adverse events were fatal, and none of the five serious adverse events noted were considered to be attributable to treatment, they added. Although anti-brodalumab neutralizing antibodies were not detected, one patient tested positive for anti-brodalumab binding antibodies.

Noting that treatment with brodalumab has been associated with significant improvements in patients with plaque psoriasis and psoriatic arthritis in phase II and III studies, “results from this study confirm that brodalumab can improve patient symptoms not long after treatment is initiated,” in patients with GPP and PsE, the authors concluded. While acknowledging the study limitations, including the open label design and a small sample size, they added, “IL-17RA blocking will be a promising therapeutic target in patients with GPP and PsE.”

The safety profile and low expression of anti-brodalumab antibodies indicated that brodalumab was suitable for long-term use, they said.

The study was funded by Kyowa Hakko Kirin. All authors disclosed ties to pharmaceutical companies, including the funding source; one author is an employee of the company.

The investigational interleukin-17 inhibitor brodalumab was safe and effective in a small phase III Japanese study of adults with two rare and severe types of psoriasis, generalized pustular psoriasis (GPP) and psoriatic erythroderma (PsE). The results were published in the British Journal of Dermatology.

The 52-week open label studyevaluated the safety and efficacy of brodalumab in 30 Japanese adults (mean age 48 years) with GPP (12 patients) and PsE (18 patients). Brodalumab, a human monoclonal antibody against human IL-17RA that blocks the biologic activities of IL-17, was administered by subcutaneous injection. Efficacy was assessed via Clinical Global Impression of Improvement (CGI) scores, the primary endpoint (Br J Dermatol. 2016 April 23. doi: 10.1111/bjd.14702).

A high proportion of patients with either disease achieved “improved” or “remission” CGI scores at weeks 2, 12, and 52, reported Dr. Kenshi Yamasaki, of the department of dermatology at Tohoku University, Miyagi, Japan, and his associates

At week 52, almost 92% of those with GPP and 100% of those with PsE had achieved “improved” or “remission” scores. The most common adverse event was nasopharyngitis, which occurred in one-third of patients. Infection-related adverse events were grade 1 or 2, no adverse events were fatal, and none of the five serious adverse events noted were considered to be attributable to treatment, they added. Although anti-brodalumab neutralizing antibodies were not detected, one patient tested positive for anti-brodalumab binding antibodies.

Noting that treatment with brodalumab has been associated with significant improvements in patients with plaque psoriasis and psoriatic arthritis in phase II and III studies, “results from this study confirm that brodalumab can improve patient symptoms not long after treatment is initiated,” in patients with GPP and PsE, the authors concluded. While acknowledging the study limitations, including the open label design and a small sample size, they added, “IL-17RA blocking will be a promising therapeutic target in patients with GPP and PsE.”

The safety profile and low expression of anti-brodalumab antibodies indicated that brodalumab was suitable for long-term use, they said.

The study was funded by Kyowa Hakko Kirin. All authors disclosed ties to pharmaceutical companies, including the funding source; one author is an employee of the company.

The investigational interleukin-17 inhibitor brodalumab was safe and effective in a small phase III Japanese study of adults with two rare and severe types of psoriasis, generalized pustular psoriasis (GPP) and psoriatic erythroderma (PsE). The results were published in the British Journal of Dermatology.

The 52-week open label studyevaluated the safety and efficacy of brodalumab in 30 Japanese adults (mean age 48 years) with GPP (12 patients) and PsE (18 patients). Brodalumab, a human monoclonal antibody against human IL-17RA that blocks the biologic activities of IL-17, was administered by subcutaneous injection. Efficacy was assessed via Clinical Global Impression of Improvement (CGI) scores, the primary endpoint (Br J Dermatol. 2016 April 23. doi: 10.1111/bjd.14702).

A high proportion of patients with either disease achieved “improved” or “remission” CGI scores at weeks 2, 12, and 52, reported Dr. Kenshi Yamasaki, of the department of dermatology at Tohoku University, Miyagi, Japan, and his associates

At week 52, almost 92% of those with GPP and 100% of those with PsE had achieved “improved” or “remission” scores. The most common adverse event was nasopharyngitis, which occurred in one-third of patients. Infection-related adverse events were grade 1 or 2, no adverse events were fatal, and none of the five serious adverse events noted were considered to be attributable to treatment, they added. Although anti-brodalumab neutralizing antibodies were not detected, one patient tested positive for anti-brodalumab binding antibodies.

Noting that treatment with brodalumab has been associated with significant improvements in patients with plaque psoriasis and psoriatic arthritis in phase II and III studies, “results from this study confirm that brodalumab can improve patient symptoms not long after treatment is initiated,” in patients with GPP and PsE, the authors concluded. While acknowledging the study limitations, including the open label design and a small sample size, they added, “IL-17RA blocking will be a promising therapeutic target in patients with GPP and PsE.”

The safety profile and low expression of anti-brodalumab antibodies indicated that brodalumab was suitable for long-term use, they said.

The study was funded by Kyowa Hakko Kirin. All authors disclosed ties to pharmaceutical companies, including the funding source; one author is an employee of the company.

CHICAGO – Improvement in psoriasis was associated with a significant reduction in coronary plaque burden within 1 year in a pilot study conducted at the National Heart, Lung, and Blood Institute, Joseph B. Lerman reported at the annual meeting of the American College of Cardiology.

“If you look at psoriatic plaque on the skin, it’s spewing out cytokines such as tumor necrosis factor–alpha and interleukin-17 which are highly linked to atherosclerosis. What we’ve found is that if you treat those plaques and reduce the severity of psoriasis, we’ve noticed small but statistically significant regression in the early noncalcified plaque. It’s a very exciting observation,” said Mr. Lerman, a medical student at Mount Sinai School of Medicine, New York.

Bruce Jancin/Frontline Medical News

He presented an observational study involving 50 consecutive patients with mild to moderate psoriasis of roughly 20 years duration and a median baseline Framingham Risk Score of 4. They underwent measurement of coronary plaque burden by coronary CT angiography at baseline and 1 year later.

During the study year, 33 patients showed significant improvement in their psoriasis as reflected in a decline in their mean Psoriasis Area and Severity Index score from 5.6 to 3.1. Those patients also showed significant improvement in their total and noncalcified plaque burden, with total plaque burden adjusted for luminal attenuation declining from 126 mm² to 117 mm². The association remained significant even after adjustment for traditional cardiovascular risk factors, the use of statin therapy, body mass index, and the use of systemic psoriasis therapies, including biologic agents.

Importantly, the reduction in plaque burden appeared to be largely concentrated in the subgroup of 31 patients on methotrexate or a biologic. And while this was a naturalistic observational study, the investigators have followed up with a prospective study of psoriasis patients placed on tumor necrosis factor inhibitors and confirmed that they, too, experienced a reduction in coronary plaque as measured by coronary CT angiography.

The investigators plan to expand the size of the study in order to confirm the findings. Mr. Lerman said the next question they would like to address is, how early does a measurable reduction in coronary plaque burden occur in response to clinical improvement in psoriasis? In order to explore this, the investigators will have to obtain institutional approval of a new investigative protocol which permits more frequent use of coronary CT angiography. At present the imaging study can be conducted only once per year due to the radiation exposure.

Mr. Lerman was involved in the psoriasis study while participating in the National Institutes of Health Medical Research Scholars Program. Senior investigator in the pilot study was Dr. Nehal Mehta, chief of the Section of Inflammation and Metabolic Disease at NHLBI in Bethesda, Md.

Mr. Lerman reported having no financial conflicts of interest.

[email protected]

CHICAGO – Improvement in psoriasis was associated with a significant reduction in coronary plaque burden within 1 year in a pilot study conducted at the National Heart, Lung, and Blood Institute, Joseph B. Lerman reported at the annual meeting of the American College of Cardiology.

“If you look at psoriatic plaque on the skin, it’s spewing out cytokines such as tumor necrosis factor–alpha and interleukin-17 which are highly linked to atherosclerosis. What we’ve found is that if you treat those plaques and reduce the severity of psoriasis, we’ve noticed small but statistically significant regression in the early noncalcified plaque. It’s a very exciting observation,” said Mr. Lerman, a medical student at Mount Sinai School of Medicine, New York.

Bruce Jancin/Frontline Medical News

He presented an observational study involving 50 consecutive patients with mild to moderate psoriasis of roughly 20 years duration and a median baseline Framingham Risk Score of 4. They underwent measurement of coronary plaque burden by coronary CT angiography at baseline and 1 year later.

During the study year, 33 patients showed significant improvement in their psoriasis as reflected in a decline in their mean Psoriasis Area and Severity Index score from 5.6 to 3.1. Those patients also showed significant improvement in their total and noncalcified plaque burden, with total plaque burden adjusted for luminal attenuation declining from 126 mm² to 117 mm². The association remained significant even after adjustment for traditional cardiovascular risk factors, the use of statin therapy, body mass index, and the use of systemic psoriasis therapies, including biologic agents.

Importantly, the reduction in plaque burden appeared to be largely concentrated in the subgroup of 31 patients on methotrexate or a biologic. And while this was a naturalistic observational study, the investigators have followed up with a prospective study of psoriasis patients placed on tumor necrosis factor inhibitors and confirmed that they, too, experienced a reduction in coronary plaque as measured by coronary CT angiography.

The investigators plan to expand the size of the study in order to confirm the findings. Mr. Lerman said the next question they would like to address is, how early does a measurable reduction in coronary plaque burden occur in response to clinical improvement in psoriasis? In order to explore this, the investigators will have to obtain institutional approval of a new investigative protocol which permits more frequent use of coronary CT angiography. At present the imaging study can be conducted only once per year due to the radiation exposure.

Mr. Lerman was involved in the psoriasis study while participating in the National Institutes of Health Medical Research Scholars Program. Senior investigator in the pilot study was Dr. Nehal Mehta, chief of the Section of Inflammation and Metabolic Disease at NHLBI in Bethesda, Md.

Mr. Lerman reported having no financial conflicts of interest.

[email protected]

CHICAGO – Improvement in psoriasis was associated with a significant reduction in coronary plaque burden within 1 year in a pilot study conducted at the National Heart, Lung, and Blood Institute, Joseph B. Lerman reported at the annual meeting of the American College of Cardiology.

“If you look at psoriatic plaque on the skin, it’s spewing out cytokines such as tumor necrosis factor–alpha and interleukin-17 which are highly linked to atherosclerosis. What we’ve found is that if you treat those plaques and reduce the severity of psoriasis, we’ve noticed small but statistically significant regression in the early noncalcified plaque. It’s a very exciting observation,” said Mr. Lerman, a medical student at Mount Sinai School of Medicine, New York.

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He presented an observational study involving 50 consecutive patients with mild to moderate psoriasis of roughly 20 years duration and a median baseline Framingham Risk Score of 4. They underwent measurement of coronary plaque burden by coronary CT angiography at baseline and 1 year later.

During the study year, 33 patients showed significant improvement in their psoriasis as reflected in a decline in their mean Psoriasis Area and Severity Index score from 5.6 to 3.1. Those patients also showed significant improvement in their total and noncalcified plaque burden, with total plaque burden adjusted for luminal attenuation declining from 126 mm² to 117 mm². The association remained significant even after adjustment for traditional cardiovascular risk factors, the use of statin therapy, body mass index, and the use of systemic psoriasis therapies, including biologic agents.

Importantly, the reduction in plaque burden appeared to be largely concentrated in the subgroup of 31 patients on methotrexate or a biologic. And while this was a naturalistic observational study, the investigators have followed up with a prospective study of psoriasis patients placed on tumor necrosis factor inhibitors and confirmed that they, too, experienced a reduction in coronary plaque as measured by coronary CT angiography.

The investigators plan to expand the size of the study in order to confirm the findings. Mr. Lerman said the next question they would like to address is, how early does a measurable reduction in coronary plaque burden occur in response to clinical improvement in psoriasis? In order to explore this, the investigators will have to obtain institutional approval of a new investigative protocol which permits more frequent use of coronary CT angiography. At present the imaging study can be conducted only once per year due to the radiation exposure.

Mr. Lerman was involved in the psoriasis study while participating in the National Institutes of Health Medical Research Scholars Program. Senior investigator in the pilot study was Dr. Nehal Mehta, chief of the Section of Inflammation and Metabolic Disease at NHLBI in Bethesda, Md.

Mr. Lerman reported having no financial conflicts of interest.

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