Ankylosing spondylitis

Most of the minority of axial spondyloarthritis patients who do not respond to their first tumor necrosis factor inhibitor still meet classification criteria for the condition 5-10 years later, but more than half respond to a second TNFi and most also have comorbidities that could affect the spondyloarthritis evaluation, according to findings from a single-center cohort study.

The study’s finding of TNFi primary inefficacy in 27 (12%) of 222 patients with axial spondyloarthritis (axSpA) who were given their first TNFi during 2004-2009 is in line with previous results of about 5%-15% primary inefficacy for a first TNFi in axSpA. However, the French investigators, led by Sandra Kossi of Cochin Hospital in Paris, noted that the difficulty of making an axSpA diagnosis and the presence of certain comorbidities “could interfere either with the activity of SpA (falsely heightened disease activity) or with the response to TNFi (falsely heightened inefficacy).” They sought to report the characteristics of axSpA patients with primary inefficacy after their first TNFi in the 5- to 10-year period after their prescription (Rheumatology [Oxford]. 2017 Jan 9. doi: 10.1093/rheumatology/kew456).

A total of 25 of the patients with primary inefficacy underwent re-evaluation 5-10 years (mean of 6 years) later. The investigators defined primary inefficacy as “treatment interruption 3-4 months after treatment onset, with a rheumatologist assessment in the medical file citing lack of efficacy as primary reason for drug interruption.”

The patients with primary TNFi inefficacy had a mean age of 53 years at the time of follow-up, and about half were female. All the patients still had symptoms and back pain, but symptoms were moderate based on a mean Bath Ankylosing Spondylitis Disease Activity Index score of 42. Overall, nine were taking a TNFi and nine were taking nonsteroidal anti-inflammatory drugs, while others used analgesics or nonpharmacologic measures.

Primary TNFi inefficacy occurred significantly more often occurred among females (48% vs. 27%; P = .04), older aged patients at first TNFi use (45 vs. 39 years; P = .04), patients with higher mean Bath Ankylosing Spondylitis Functional Index scores (68 vs. 42; P = .03), and in those who did not have an abnormally elevated C-reactive protein level (33% vs. 63%; P = .02). Patients with primary TNFi inefficacy had lower rates of HLAB27 positivity (56% vs. 72%) or radiographic sacroiliitis (67% vs. 81%), but the differences were not statistically significant.

At follow-up, 21 (84%) patients met Assessment of Spondyloarthritis International Society classification criteria for axSpA, and 20 (80%) met the axSpA diagnosis according to the rheumatologists’ opinion, with 17 (68%) fulfilling both.

A total of 18 (72%) had at least one of the following comorbidities: widespread pain syndrome, osteoarthritis, or depression. Five patients – all females – had widespread pain syndrome according to the Fibromyalgia Rapid Screening Tool questionnaire. Another 10 patients had osteoarthritis of lower-limb peripheral joints or of the spine, while an additional 8 had self-declared depression, for which 3 were taking antidepressants.

By the time of follow-up, 16 (64%) had switched to another TNFi, including 9 who had received two TNFi drugs and 7 who had received three or more. The second TNFi was considered efficacious in nine patients. The retention rate of the second TNFi at 1 year among those with primary inefficacy was 50%, and overall, nine patients were still prescribed a TNFi at the time of follow-up.

The fact that most of the patients with primary inefficacy to their first TNFi had confirmed axSpA but also had comorbidities that could affect axSpA evaluation “is important because practitioners might consider that primary inefficacy to TNFi leads to reconsidering the diagnosis of SpA (i.e. the notion of a TNFi prescription being used as the diagnostic test). We suggest here that primary inefficacy should not be considered as equivalent to a diagnostic error, and that a second prescription of TNFi may be of use in such patients, although painful comorbidities should certainly be screened for and taken into account.”

The study was funded by the Assistance Publique des Hôpitaux de Paris. The investigators had no conflicts of interest to declare.

[email protected]

Most of the minority of axial spondyloarthritis patients who do not respond to their first tumor necrosis factor inhibitor still meet classification criteria for the condition 5-10 years later, but more than half respond to a second TNFi and most also have comorbidities that could affect the spondyloarthritis evaluation, according to findings from a single-center cohort study.

The study’s finding of TNFi primary inefficacy in 27 (12%) of 222 patients with axial spondyloarthritis (axSpA) who were given their first TNFi during 2004-2009 is in line with previous results of about 5%-15% primary inefficacy for a first TNFi in axSpA. However, the French investigators, led by Sandra Kossi of Cochin Hospital in Paris, noted that the difficulty of making an axSpA diagnosis and the presence of certain comorbidities “could interfere either with the activity of SpA (falsely heightened disease activity) or with the response to TNFi (falsely heightened inefficacy).” They sought to report the characteristics of axSpA patients with primary inefficacy after their first TNFi in the 5- to 10-year period after their prescription (Rheumatology [Oxford]. 2017 Jan 9. doi: 10.1093/rheumatology/kew456).

A total of 25 of the patients with primary inefficacy underwent re-evaluation 5-10 years (mean of 6 years) later. The investigators defined primary inefficacy as “treatment interruption 3-4 months after treatment onset, with a rheumatologist assessment in the medical file citing lack of efficacy as primary reason for drug interruption.”

The patients with primary TNFi inefficacy had a mean age of 53 years at the time of follow-up, and about half were female. All the patients still had symptoms and back pain, but symptoms were moderate based on a mean Bath Ankylosing Spondylitis Disease Activity Index score of 42. Overall, nine were taking a TNFi and nine were taking nonsteroidal anti-inflammatory drugs, while others used analgesics or nonpharmacologic measures.

Primary TNFi inefficacy occurred significantly more often occurred among females (48% vs. 27%; P = .04), older aged patients at first TNFi use (45 vs. 39 years; P = .04), patients with higher mean Bath Ankylosing Spondylitis Functional Index scores (68 vs. 42; P = .03), and in those who did not have an abnormally elevated C-reactive protein level (33% vs. 63%; P = .02). Patients with primary TNFi inefficacy had lower rates of HLAB27 positivity (56% vs. 72%) or radiographic sacroiliitis (67% vs. 81%), but the differences were not statistically significant.

At follow-up, 21 (84%) patients met Assessment of Spondyloarthritis International Society classification criteria for axSpA, and 20 (80%) met the axSpA diagnosis according to the rheumatologists’ opinion, with 17 (68%) fulfilling both.

A total of 18 (72%) had at least one of the following comorbidities: widespread pain syndrome, osteoarthritis, or depression. Five patients – all females – had widespread pain syndrome according to the Fibromyalgia Rapid Screening Tool questionnaire. Another 10 patients had osteoarthritis of lower-limb peripheral joints or of the spine, while an additional 8 had self-declared depression, for which 3 were taking antidepressants.

By the time of follow-up, 16 (64%) had switched to another TNFi, including 9 who had received two TNFi drugs and 7 who had received three or more. The second TNFi was considered efficacious in nine patients. The retention rate of the second TNFi at 1 year among those with primary inefficacy was 50%, and overall, nine patients were still prescribed a TNFi at the time of follow-up.

The fact that most of the patients with primary inefficacy to their first TNFi had confirmed axSpA but also had comorbidities that could affect axSpA evaluation “is important because practitioners might consider that primary inefficacy to TNFi leads to reconsidering the diagnosis of SpA (i.e. the notion of a TNFi prescription being used as the diagnostic test). We suggest here that primary inefficacy should not be considered as equivalent to a diagnostic error, and that a second prescription of TNFi may be of use in such patients, although painful comorbidities should certainly be screened for and taken into account.”

The study was funded by the Assistance Publique des Hôpitaux de Paris. The investigators had no conflicts of interest to declare.

[email protected]

Most of the minority of axial spondyloarthritis patients who do not respond to their first tumor necrosis factor inhibitor still meet classification criteria for the condition 5-10 years later, but more than half respond to a second TNFi and most also have comorbidities that could affect the spondyloarthritis evaluation, according to findings from a single-center cohort study.

The study’s finding of TNFi primary inefficacy in 27 (12%) of 222 patients with axial spondyloarthritis (axSpA) who were given their first TNFi during 2004-2009 is in line with previous results of about 5%-15% primary inefficacy for a first TNFi in axSpA. However, the French investigators, led by Sandra Kossi of Cochin Hospital in Paris, noted that the difficulty of making an axSpA diagnosis and the presence of certain comorbidities “could interfere either with the activity of SpA (falsely heightened disease activity) or with the response to TNFi (falsely heightened inefficacy).” They sought to report the characteristics of axSpA patients with primary inefficacy after their first TNFi in the 5- to 10-year period after their prescription (Rheumatology [Oxford]. 2017 Jan 9. doi: 10.1093/rheumatology/kew456).

A total of 25 of the patients with primary inefficacy underwent re-evaluation 5-10 years (mean of 6 years) later. The investigators defined primary inefficacy as “treatment interruption 3-4 months after treatment onset, with a rheumatologist assessment in the medical file citing lack of efficacy as primary reason for drug interruption.”

The patients with primary TNFi inefficacy had a mean age of 53 years at the time of follow-up, and about half were female. All the patients still had symptoms and back pain, but symptoms were moderate based on a mean Bath Ankylosing Spondylitis Disease Activity Index score of 42. Overall, nine were taking a TNFi and nine were taking nonsteroidal anti-inflammatory drugs, while others used analgesics or nonpharmacologic measures.

Primary TNFi inefficacy occurred significantly more often occurred among females (48% vs. 27%; P = .04), older aged patients at first TNFi use (45 vs. 39 years; P = .04), patients with higher mean Bath Ankylosing Spondylitis Functional Index scores (68 vs. 42; P = .03), and in those who did not have an abnormally elevated C-reactive protein level (33% vs. 63%; P = .02). Patients with primary TNFi inefficacy had lower rates of HLAB27 positivity (56% vs. 72%) or radiographic sacroiliitis (67% vs. 81%), but the differences were not statistically significant.

At follow-up, 21 (84%) patients met Assessment of Spondyloarthritis International Society classification criteria for axSpA, and 20 (80%) met the axSpA diagnosis according to the rheumatologists’ opinion, with 17 (68%) fulfilling both.

A total of 18 (72%) had at least one of the following comorbidities: widespread pain syndrome, osteoarthritis, or depression. Five patients – all females – had widespread pain syndrome according to the Fibromyalgia Rapid Screening Tool questionnaire. Another 10 patients had osteoarthritis of lower-limb peripheral joints or of the spine, while an additional 8 had self-declared depression, for which 3 were taking antidepressants.

By the time of follow-up, 16 (64%) had switched to another TNFi, including 9 who had received two TNFi drugs and 7 who had received three or more. The second TNFi was considered efficacious in nine patients. The retention rate of the second TNFi at 1 year among those with primary inefficacy was 50%, and overall, nine patients were still prescribed a TNFi at the time of follow-up.

The fact that most of the patients with primary inefficacy to their first TNFi had confirmed axSpA but also had comorbidities that could affect axSpA evaluation “is important because practitioners might consider that primary inefficacy to TNFi leads to reconsidering the diagnosis of SpA (i.e. the notion of a TNFi prescription being used as the diagnostic test). We suggest here that primary inefficacy should not be considered as equivalent to a diagnostic error, and that a second prescription of TNFi may be of use in such patients, although painful comorbidities should certainly be screened for and taken into account.”

The study was funded by the Assistance Publique des Hôpitaux de Paris. The investigators had no conflicts of interest to declare.

[email protected]

Payment for the infliximab biosimilar drug Inflectra will now be covered by Medicare, the drug’s manufacturer, Pfizer, said in an announcement.

The Centers for Medicare & Medicaid Services (CMS) included Inflectra (infliximab-dyyb) in its January 2017 Average Sales Price pricing file, which went into effect Jan. 1, 2017. Pfizer said that Inflectra is priced at a 15% discount to the current wholesale acquisition cost for the infliximab originator Remicade, but this price does not include discounts to payers, providers, distributors, and other purchasing organizations.

For the first quarter of 2017, the payment limit set by the CMS for Inflectra is $100.306 per 10-mg unit and $82.218 for Remicade.

Various national and regional wholesalers across the country began receiving shipments of Inflectra in November 2016, according to Pfizer.

In conjunction with the availability of Inflectra, Pfizer announced its enCompass program, “a comprehensive reimbursement service and patient support program offering coding and reimbursement support for providers, copay assistance to eligible patients who have commercial insurance that covers Inflectra, and financial assistance for eligible uninsured and underinsured patients.”

The FDA approved Inflectra in April 2016 for all of the same indications as Remicade: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, plaque psoriasis, and ulcerative colitis.

[email protected]

Payment for the infliximab biosimilar drug Inflectra will now be covered by Medicare, the drug’s manufacturer, Pfizer, said in an announcement.

The Centers for Medicare & Medicaid Services (CMS) included Inflectra (infliximab-dyyb) in its January 2017 Average Sales Price pricing file, which went into effect Jan. 1, 2017. Pfizer said that Inflectra is priced at a 15% discount to the current wholesale acquisition cost for the infliximab originator Remicade, but this price does not include discounts to payers, providers, distributors, and other purchasing organizations.

For the first quarter of 2017, the payment limit set by the CMS for Inflectra is $100.306 per 10-mg unit and $82.218 for Remicade.

Various national and regional wholesalers across the country began receiving shipments of Inflectra in November 2016, according to Pfizer.

In conjunction with the availability of Inflectra, Pfizer announced its enCompass program, “a comprehensive reimbursement service and patient support program offering coding and reimbursement support for providers, copay assistance to eligible patients who have commercial insurance that covers Inflectra, and financial assistance for eligible uninsured and underinsured patients.”

The FDA approved Inflectra in April 2016 for all of the same indications as Remicade: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, plaque psoriasis, and ulcerative colitis.

[email protected]

Payment for the infliximab biosimilar drug Inflectra will now be covered by Medicare, the drug’s manufacturer, Pfizer, said in an announcement.

The Centers for Medicare & Medicaid Services (CMS) included Inflectra (infliximab-dyyb) in its January 2017 Average Sales Price pricing file, which went into effect Jan. 1, 2017. Pfizer said that Inflectra is priced at a 15% discount to the current wholesale acquisition cost for the infliximab originator Remicade, but this price does not include discounts to payers, providers, distributors, and other purchasing organizations.

For the first quarter of 2017, the payment limit set by the CMS for Inflectra is $100.306 per 10-mg unit and $82.218 for Remicade.

Various national and regional wholesalers across the country began receiving shipments of Inflectra in November 2016, according to Pfizer.

In conjunction with the availability of Inflectra, Pfizer announced its enCompass program, “a comprehensive reimbursement service and patient support program offering coding and reimbursement support for providers, copay assistance to eligible patients who have commercial insurance that covers Inflectra, and financial assistance for eligible uninsured and underinsured patients.”

The FDA approved Inflectra in April 2016 for all of the same indications as Remicade: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, plaque psoriasis, and ulcerative colitis.

[email protected]

WASHINGTON – Women are almost twice as likely as men to develop extra-articular manifestations of ankylosing spondylitis such as uveitis and inflammatory bowel disease, according to an analysis of patients in the Ankylosing Spondylitis Registry of Ireland.

Each of those manifestations exerts its own difficulties upon patients over and above the inflammatory back pain of the underlying disease, Gillian Fitzgerald, MD, said at the annual meeting of the American College of Rheumatology. Many patients can develop several of these separate manifestations – a circumstance that seriously affects their quality of life.

The findings of the large registry study were a bit surprising, she said during presentation of the study at a press briefing, as ankylosing spondylitis is generally thought to affect largely men. “However, this isn’t the case,” said Dr. Fitzgerald of St. James’s Hospital, Dublin. “Recent studies show that women can be affected as often as men are.”

In light of those findings, Dr. Fitzgerald and her coauthors wanted to further define the gender differences, especially with regard to extra-articular manifestations.

They accessed data on 564 patients in the registry, which was established in 2013. The majority of patients (78%) were men; the mean age was 47 years. Patients had a mean disease duration of nearly 21 years. For almost half that time (9 years) they had remained undiagnosed, Dr. Fitzgerald added. They had a mean age of about 47 years, and 78% fulfilled the modified New York criteria for ankylosing spondylitis.

Overall, extra-articular manifestations were common, with 35% having uveitis, 18% psoriasis, and 10% inflammatory bowel disease.

Uveitis was significantly more common among women (47% vs. 32%) and among those with disease duration of more than 10 years (40% vs. 22% with less than 10 years).

Inflammatory bowel disease was also significantly more common among women (16.5% vs. 8%). It wasn’t related to disease duration, but it was related to elevated baseline C-reactive protein, peptic ulcer disease, and osteoporosis.

In a multivariate regression analysis, women were 70% more likely to experience an extra-articular manifestation of the disease than were men (hazard ratio, 1.7). Having the disease for more than 10 years more than doubled the risk of an extra-articular manifestation (HR, 2.4).

Dr. Fitzgerald discussed the study’s findings in a video interview at the meeting. She had no financial disclosures.

[email protected]

On Twitter @alz_gal

WASHINGTON – Women are almost twice as likely as men to develop extra-articular manifestations of ankylosing spondylitis such as uveitis and inflammatory bowel disease, according to an analysis of patients in the Ankylosing Spondylitis Registry of Ireland.

Each of those manifestations exerts its own difficulties upon patients over and above the inflammatory back pain of the underlying disease, Gillian Fitzgerald, MD, said at the annual meeting of the American College of Rheumatology. Many patients can develop several of these separate manifestations – a circumstance that seriously affects their quality of life.

The findings of the large registry study were a bit surprising, she said during presentation of the study at a press briefing, as ankylosing spondylitis is generally thought to affect largely men. “However, this isn’t the case,” said Dr. Fitzgerald of St. James’s Hospital, Dublin. “Recent studies show that women can be affected as often as men are.”

In light of those findings, Dr. Fitzgerald and her coauthors wanted to further define the gender differences, especially with regard to extra-articular manifestations.

They accessed data on 564 patients in the registry, which was established in 2013. The majority of patients (78%) were men; the mean age was 47 years. Patients had a mean disease duration of nearly 21 years. For almost half that time (9 years) they had remained undiagnosed, Dr. Fitzgerald added. They had a mean age of about 47 years, and 78% fulfilled the modified New York criteria for ankylosing spondylitis.

Overall, extra-articular manifestations were common, with 35% having uveitis, 18% psoriasis, and 10% inflammatory bowel disease.

Uveitis was significantly more common among women (47% vs. 32%) and among those with disease duration of more than 10 years (40% vs. 22% with less than 10 years).

Inflammatory bowel disease was also significantly more common among women (16.5% vs. 8%). It wasn’t related to disease duration, but it was related to elevated baseline C-reactive protein, peptic ulcer disease, and osteoporosis.

In a multivariate regression analysis, women were 70% more likely to experience an extra-articular manifestation of the disease than were men (hazard ratio, 1.7). Having the disease for more than 10 years more than doubled the risk of an extra-articular manifestation (HR, 2.4).

Dr. Fitzgerald discussed the study’s findings in a video interview at the meeting. She had no financial disclosures.

[email protected]

On Twitter @alz_gal

WASHINGTON – Women are almost twice as likely as men to develop extra-articular manifestations of ankylosing spondylitis such as uveitis and inflammatory bowel disease, according to an analysis of patients in the Ankylosing Spondylitis Registry of Ireland.

Each of those manifestations exerts its own difficulties upon patients over and above the inflammatory back pain of the underlying disease, Gillian Fitzgerald, MD, said at the annual meeting of the American College of Rheumatology. Many patients can develop several of these separate manifestations – a circumstance that seriously affects their quality of life.

The findings of the large registry study were a bit surprising, she said during presentation of the study at a press briefing, as ankylosing spondylitis is generally thought to affect largely men. “However, this isn’t the case,” said Dr. Fitzgerald of St. James’s Hospital, Dublin. “Recent studies show that women can be affected as often as men are.”

In light of those findings, Dr. Fitzgerald and her coauthors wanted to further define the gender differences, especially with regard to extra-articular manifestations.

They accessed data on 564 patients in the registry, which was established in 2013. The majority of patients (78%) were men; the mean age was 47 years. Patients had a mean disease duration of nearly 21 years. For almost half that time (9 years) they had remained undiagnosed, Dr. Fitzgerald added. They had a mean age of about 47 years, and 78% fulfilled the modified New York criteria for ankylosing spondylitis.

Overall, extra-articular manifestations were common, with 35% having uveitis, 18% psoriasis, and 10% inflammatory bowel disease.

Uveitis was significantly more common among women (47% vs. 32%) and among those with disease duration of more than 10 years (40% vs. 22% with less than 10 years).

Inflammatory bowel disease was also significantly more common among women (16.5% vs. 8%). It wasn’t related to disease duration, but it was related to elevated baseline C-reactive protein, peptic ulcer disease, and osteoporosis.

In a multivariate regression analysis, women were 70% more likely to experience an extra-articular manifestation of the disease than were men (hazard ratio, 1.7). Having the disease for more than 10 years more than doubled the risk of an extra-articular manifestation (HR, 2.4).

Dr. Fitzgerald discussed the study’s findings in a video interview at the meeting. She had no financial disclosures.

[email protected]

On Twitter @alz_gal

WASHINGTON – Statins lowered all-cause mortality by 32% in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in a retrospective cohort study.

The magnitude of benefit from statins in these two disease states is greater than that found in the general population (estimated 9%-14% reduction in all-cause mortality) and than that reported in patients with rheumatoid arthritis (RA, 21% reduction), said Amar Oza, MD, a second-year rheumatology fellow at Massachusetts General Hospital and Harvard Medical School, both in Boston.

“This is a unique study. The benefit of statins has not been looked at in AS and PsA, specifically,” Dr. Oza explained. “More data are needed” to establish this benefit with certainty, he added.

The data were presented at the annual meeting of the American College of Rheumatology, and Dr. Oza discussed the findings in a video interview.

The study compared 2,904 patients with AS or PsA who initiated statins between 2000 and 2014 with 2,904 propensity-matched AS or PsA patients who did not initiate statins during that period. Patients were drawn from a United Kingdom general population database.

The investigators used a propensity score that accounted for 50 confounding variables to match the two cohorts. These variables included, but were not limited to, disease duration, socioeconomic status, body mass index, lifestyle factors, and medication use.

“This study is the first step in elucidating the benefit of statins in AS and PsA. It is a good step forward. If additional data substantiate that AS and PsA patients have a low threshold for statins, I can envision statins for both primary and secondary prevention in this patient population,” Dr. Oza stated.

The authors had no relevant financial disclosures.

WASHINGTON – Statins lowered all-cause mortality by 32% in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in a retrospective cohort study.

The magnitude of benefit from statins in these two disease states is greater than that found in the general population (estimated 9%-14% reduction in all-cause mortality) and than that reported in patients with rheumatoid arthritis (RA, 21% reduction), said Amar Oza, MD, a second-year rheumatology fellow at Massachusetts General Hospital and Harvard Medical School, both in Boston.

“This is a unique study. The benefit of statins has not been looked at in AS and PsA, specifically,” Dr. Oza explained. “More data are needed” to establish this benefit with certainty, he added.

The data were presented at the annual meeting of the American College of Rheumatology, and Dr. Oza discussed the findings in a video interview.

The study compared 2,904 patients with AS or PsA who initiated statins between 2000 and 2014 with 2,904 propensity-matched AS or PsA patients who did not initiate statins during that period. Patients were drawn from a United Kingdom general population database.

The investigators used a propensity score that accounted for 50 confounding variables to match the two cohorts. These variables included, but were not limited to, disease duration, socioeconomic status, body mass index, lifestyle factors, and medication use.

“This study is the first step in elucidating the benefit of statins in AS and PsA. It is a good step forward. If additional data substantiate that AS and PsA patients have a low threshold for statins, I can envision statins for both primary and secondary prevention in this patient population,” Dr. Oza stated.

The authors had no relevant financial disclosures.

WASHINGTON – Statins lowered all-cause mortality by 32% in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in a retrospective cohort study.

The magnitude of benefit from statins in these two disease states is greater than that found in the general population (estimated 9%-14% reduction in all-cause mortality) and than that reported in patients with rheumatoid arthritis (RA, 21% reduction), said Amar Oza, MD, a second-year rheumatology fellow at Massachusetts General Hospital and Harvard Medical School, both in Boston.

“This is a unique study. The benefit of statins has not been looked at in AS and PsA, specifically,” Dr. Oza explained. “More data are needed” to establish this benefit with certainty, he added.

The data were presented at the annual meeting of the American College of Rheumatology, and Dr. Oza discussed the findings in a video interview.

The study compared 2,904 patients with AS or PsA who initiated statins between 2000 and 2014 with 2,904 propensity-matched AS or PsA patients who did not initiate statins during that period. Patients were drawn from a United Kingdom general population database.

The investigators used a propensity score that accounted for 50 confounding variables to match the two cohorts. These variables included, but were not limited to, disease duration, socioeconomic status, body mass index, lifestyle factors, and medication use.

“This study is the first step in elucidating the benefit of statins in AS and PsA. It is a good step forward. If additional data substantiate that AS and PsA patients have a low threshold for statins, I can envision statins for both primary and secondary prevention in this patient population,” Dr. Oza stated.

The authors had no relevant financial disclosures.

WASHINGTON – Certolizumab pegol is not transmitted into human breast milk in any clinically meaningful level, a postmarketing pharmacokinetic study has determined.

While there were individual differences in how much of the TNF inhibitor did cross into milk, none of the 17 women in the study transmitted more than 0.076 mcg/mL in any sample, Megan Clowse, MD, said at the annual meeting of the American College of Rheumatology.

“This is well below even 1% of the expected plasma concentration of a therapeutic dose,” said Dr. Clowse, a rheumatologist and director of the Duke Autoimmunity in Pregnancy Registry at Duke University, Durham, N.C. “Additionally, the mean relative infant dose was 0.125% – also far below the cutoff of less than 10% of the adult dose, the level generally thought to be of little concern for infant well-being.”

©Jupiterimages/Thinkstock

[email protected]

On Twitter @alz_gal

WASHINGTON – Certolizumab pegol is not transmitted into human breast milk in any clinically meaningful level, a postmarketing pharmacokinetic study has determined.

While there were individual differences in how much of the TNF inhibitor did cross into milk, none of the 17 women in the study transmitted more than 0.076 mcg/mL in any sample, Megan Clowse, MD, said at the annual meeting of the American College of Rheumatology.

“This is well below even 1% of the expected plasma concentration of a therapeutic dose,” said Dr. Clowse, a rheumatologist and director of the Duke Autoimmunity in Pregnancy Registry at Duke University, Durham, N.C. “Additionally, the mean relative infant dose was 0.125% – also far below the cutoff of less than 10% of the adult dose, the level generally thought to be of little concern for infant well-being.”

©Jupiterimages/Thinkstock

[email protected]

On Twitter @alz_gal

WASHINGTON – Certolizumab pegol is not transmitted into human breast milk in any clinically meaningful level, a postmarketing pharmacokinetic study has determined.

While there were individual differences in how much of the TNF inhibitor did cross into milk, none of the 17 women in the study transmitted more than 0.076 mcg/mL in any sample, Megan Clowse, MD, said at the annual meeting of the American College of Rheumatology.

“This is well below even 1% of the expected plasma concentration of a therapeutic dose,” said Dr. Clowse, a rheumatologist and director of the Duke Autoimmunity in Pregnancy Registry at Duke University, Durham, N.C. “Additionally, the mean relative infant dose was 0.125% – also far below the cutoff of less than 10% of the adult dose, the level generally thought to be of little concern for infant well-being.”

©Jupiterimages/Thinkstock

[email protected]

On Twitter @alz_gal

WASHINGTON – Data from the first randomized trial of switching from an originator biologic to a biosimilar of the originator indicate that the infliximab biosimilar Remsima is no different from the infliximab originator Remicade in the rate of disease worsening over 1 year across a combination of all its approved indications.

The outcomes of the Norwegian, double-blind, noninferiority trial, called NOR-SWITCH, indicate similar rates of disease worsening across patients switched to Remsima and those who stayed on Remicade. However, exploratory group analyses conducted on the different disease subgroups in the trial (Crohn’s disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriasis, and psoriatic arthritis) showed a potentially concerning level of disease worsening among Crohn’s disease patients on Remsima with a confidence interval that nearly fell entirely within the range favoring Remicade.

In the United States, Remsima, also known as CT-P13, is marketed by Pfizer as Inflectra.

WASHINGTON – Data from the first randomized trial of switching from an originator biologic to a biosimilar of the originator indicate that the infliximab biosimilar Remsima is no different from the infliximab originator Remicade in the rate of disease worsening over 1 year across a combination of all its approved indications.

The outcomes of the Norwegian, double-blind, noninferiority trial, called NOR-SWITCH, indicate similar rates of disease worsening across patients switched to Remsima and those who stayed on Remicade. However, exploratory group analyses conducted on the different disease subgroups in the trial (Crohn’s disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriasis, and psoriatic arthritis) showed a potentially concerning level of disease worsening among Crohn’s disease patients on Remsima with a confidence interval that nearly fell entirely within the range favoring Remicade.

In the United States, Remsima, also known as CT-P13, is marketed by Pfizer as Inflectra.

WASHINGTON – Data from the first randomized trial of switching from an originator biologic to a biosimilar of the originator indicate that the infliximab biosimilar Remsima is no different from the infliximab originator Remicade in the rate of disease worsening over 1 year across a combination of all its approved indications.

The outcomes of the Norwegian, double-blind, noninferiority trial, called NOR-SWITCH, indicate similar rates of disease worsening across patients switched to Remsima and those who stayed on Remicade. However, exploratory group analyses conducted on the different disease subgroups in the trial (Crohn’s disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriasis, and psoriatic arthritis) showed a potentially concerning level of disease worsening among Crohn’s disease patients on Remsima with a confidence interval that nearly fell entirely within the range favoring Remicade.

In the United States, Remsima, also known as CT-P13, is marketed by Pfizer as Inflectra.

BOSTON – Biosimilar versions of disease-modifying antirheumatic drugs have arrived in the United States, but even the best, most efficacious drugs are worthless if patients don’t want to take them.

“The science is important, the medicine is important, but at the end of the day, acceptance and use is what’s going to measure success,” said Seth D. Ginsberg, at a biosimilars symposium sponsored by Corrona, a business that provides registry data and consulting services to biopharmaceutical companies.

Ingram/thinkstock

Biosimilar confidence

His group has launched “Operation: Biosimilar Confidence” which is designed to educate patients and physicians about the clinical value and scientific underpinnings of biosimilars, as well as the thorough development, review, and regulatory processes involved.

The goal of the project is to instill confidence in patients by helping them to understand the manufacturer’s safety track record, reliability of the biosimilar supply chain, and the availability to them of support services, if they make the switch to a biosimilar.

“Generics don’t have equivalent patient-support programs, and the projection is theoretically that [biosimilar] manufacturers won’t either. We will not accept that. We are going to do everything we can for those patients, to advocate for the continuation of the support programs that we rely on as patients,” he said.

Patient concerns

Surveys of patient concerns about biosimilars have highlighted four key areas:

• What is the manufacturer’s overall safety record in both biologic agents and small-molecule therapies?
• Supply-chain logistic – Will the manufacturer commit to consistent production and supply?
• Will biosimilar manufacturers provide patient support at levels equal to those offered by innovator biologic makers, and what kind of support will be available – phone, websites, social media, copays, etc.?
• Payer ethics – Will payers offer lower copays, deductibles, or premiums, and are payers as concerned as patients about product safety, supply chain, and support?

The implementation strategy for the campaign will focus on speaking directly to patients through CreakyJoints.org, partner Global Healthy Living Foundation, patient and physician organizations, social and conventional media, advertising, and one-on-one encounters.

“We have to talk directly and indirectly to employers and employee-advocacy groups. We have to let these big self-insured employers understand what the perspective of the patient is and what life is like thanks to these medicine, and why biosimilars are a critical component to the success of living with these conditions,” he said.

Advocates also have to work with the media to create “a surround-sound message that reaches all audiences with additional frequency.”

“We cannot allow Wall Street Journal business analysts to dictate the conversations about biosimilars. Why? They’re looking at one thing, and only one thing, and they’re ignoring the patient perspective,” Ginsberg said.

Lastly, patient groups need to work closely with payers, physician groups, and manufacturers to ensure that biosimilars can be smoothly integrated into the healthcare system, he emphasized.

“I want to be crystal clear here: We can’t wait for biosimilars. Bring it on! We want them,” he said.

BOSTON – Biosimilar versions of disease-modifying antirheumatic drugs have arrived in the United States, but even the best, most efficacious drugs are worthless if patients don’t want to take them.

“The science is important, the medicine is important, but at the end of the day, acceptance and use is what’s going to measure success,” said Seth D. Ginsberg, at a biosimilars symposium sponsored by Corrona, a business that provides registry data and consulting services to biopharmaceutical companies.

Ingram/thinkstock

Biosimilar confidence

His group has launched “Operation: Biosimilar Confidence” which is designed to educate patients and physicians about the clinical value and scientific underpinnings of biosimilars, as well as the thorough development, review, and regulatory processes involved.

The goal of the project is to instill confidence in patients by helping them to understand the manufacturer’s safety track record, reliability of the biosimilar supply chain, and the availability to them of support services, if they make the switch to a biosimilar.

“Generics don’t have equivalent patient-support programs, and the projection is theoretically that [biosimilar] manufacturers won’t either. We will not accept that. We are going to do everything we can for those patients, to advocate for the continuation of the support programs that we rely on as patients,” he said.

Patient concerns

Surveys of patient concerns about biosimilars have highlighted four key areas:

• What is the manufacturer’s overall safety record in both biologic agents and small-molecule therapies?
• Supply-chain logistic – Will the manufacturer commit to consistent production and supply?
• Will biosimilar manufacturers provide patient support at levels equal to those offered by innovator biologic makers, and what kind of support will be available – phone, websites, social media, copays, etc.?
• Payer ethics – Will payers offer lower copays, deductibles, or premiums, and are payers as concerned as patients about product safety, supply chain, and support?

The implementation strategy for the campaign will focus on speaking directly to patients through CreakyJoints.org, partner Global Healthy Living Foundation, patient and physician organizations, social and conventional media, advertising, and one-on-one encounters.

“We have to talk directly and indirectly to employers and employee-advocacy groups. We have to let these big self-insured employers understand what the perspective of the patient is and what life is like thanks to these medicine, and why biosimilars are a critical component to the success of living with these conditions,” he said.

Advocates also have to work with the media to create “a surround-sound message that reaches all audiences with additional frequency.”

“We cannot allow Wall Street Journal business analysts to dictate the conversations about biosimilars. Why? They’re looking at one thing, and only one thing, and they’re ignoring the patient perspective,” Ginsberg said.

Lastly, patient groups need to work closely with payers, physician groups, and manufacturers to ensure that biosimilars can be smoothly integrated into the healthcare system, he emphasized.

“I want to be crystal clear here: We can’t wait for biosimilars. Bring it on! We want them,” he said.

BOSTON – Biosimilar versions of disease-modifying antirheumatic drugs have arrived in the United States, but even the best, most efficacious drugs are worthless if patients don’t want to take them.

“The science is important, the medicine is important, but at the end of the day, acceptance and use is what’s going to measure success,” said Seth D. Ginsberg, at a biosimilars symposium sponsored by Corrona, a business that provides registry data and consulting services to biopharmaceutical companies.

Ingram/thinkstock

Biosimilar confidence

His group has launched “Operation: Biosimilar Confidence” which is designed to educate patients and physicians about the clinical value and scientific underpinnings of biosimilars, as well as the thorough development, review, and regulatory processes involved.

The goal of the project is to instill confidence in patients by helping them to understand the manufacturer’s safety track record, reliability of the biosimilar supply chain, and the availability to them of support services, if they make the switch to a biosimilar.

“Generics don’t have equivalent patient-support programs, and the projection is theoretically that [biosimilar] manufacturers won’t either. We will not accept that. We are going to do everything we can for those patients, to advocate for the continuation of the support programs that we rely on as patients,” he said.

Patient concerns

Surveys of patient concerns about biosimilars have highlighted four key areas:

• What is the manufacturer’s overall safety record in both biologic agents and small-molecule therapies?
• Supply-chain logistic – Will the manufacturer commit to consistent production and supply?
• Will biosimilar manufacturers provide patient support at levels equal to those offered by innovator biologic makers, and what kind of support will be available – phone, websites, social media, copays, etc.?
• Payer ethics – Will payers offer lower copays, deductibles, or premiums, and are payers as concerned as patients about product safety, supply chain, and support?

The implementation strategy for the campaign will focus on speaking directly to patients through CreakyJoints.org, partner Global Healthy Living Foundation, patient and physician organizations, social and conventional media, advertising, and one-on-one encounters.

“We have to talk directly and indirectly to employers and employee-advocacy groups. We have to let these big self-insured employers understand what the perspective of the patient is and what life is like thanks to these medicine, and why biosimilars are a critical component to the success of living with these conditions,” he said.

Advocates also have to work with the media to create “a surround-sound message that reaches all audiences with additional frequency.”

“We cannot allow Wall Street Journal business analysts to dictate the conversations about biosimilars. Why? They’re looking at one thing, and only one thing, and they’re ignoring the patient perspective,” Ginsberg said.

Lastly, patient groups need to work closely with payers, physician groups, and manufacturers to ensure that biosimilars can be smoothly integrated into the healthcare system, he emphasized.

“I want to be crystal clear here: We can’t wait for biosimilars. Bring it on! We want them,” he said.

BOSTON – Biosimilar drugs are not identical twins of original biologic agents, but there are very strong family ties, and the newcomer is expected to look and behave very much like its older relative, said Janet Woodcock, MD, director of the Center for Drug Evaluation and Research at the Food and Drug Administration.

Although biosimilars differ from generic, small-molecule drugs, concerns about the development of biosimilars mirrors the kerfuffle over generic drugs surrounding the passage of the Hatch-Waxman (Drug Price Competition and Patent Term Restoration) Act in 1984.

• Are biosimilars as effective and as safe as the originally licensed biopharmaceuticals?
• If pharmacists substitute biosimilars for prescribed biologics, will patients be adversely affected?
• Can biosimilars reduce the high cost of biologic therapy?

“In certain specialties, this skepticism has persisted to this very day,” she said.

ACA mandate

Biosimilars owe their existence in large measure to the Biologics Price Competition and Innovation Act of 2009 (BPCI), passed as a part of the Affordable Care Act and signed into law by President Obama in 2010.

The act created an abbreviated licensure pathway for biologic products that can be shown to be either biosimilar to or interchangeable with an FDA-licensed reference drug.

A biosimilar is defined as a biological product that is highly similar to the reference product “notwithstanding minor differences in clinically inactive components,” and with no clinically meaningful differences between it and the reference product in terms of purity, safety, and potency.

To be interchangeable, a biosimilar must be expected to produce the same clinical results as the reference drug in any given patient, and “for a product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the product and its reference product is not greater than the risk of using the reference product without such alternation or switch.”

The definition of interchangeability includes the understanding that the prescriber’s approval is not necessary for substitution of a biosimilar for its reference product.

“If we’re going to have that kind of switching, if they are going to be interchangeable, then we have to have a very high bar,” Dr. Woodcock said.

She added that “any pressure people are feeling to push their patients to biosimilars is from the reimbursement system. There is no non-prescriber switching allowed currently; however, that doesn’t say there isn’t pressure on prescribers to write a different prescription.”

Faster track and bridge to approval

The biosimilar development and approval requires only convincing demonstration of biosimilarity to an existing agent, rather than an independent finding of safety or effectiveness, and the purpose of clinical studies in this case is to address “residual uncertainties,” Dr. Woodcock said.

Drug developers and regulatory authorities alike “are having trouble getting their mind around this concept,” she said.

The FDA requires manufacturers to provide data in their biosimilar drug license applications demonstrating biosimilarity based on analytical studies, animal studies that include toxicity assessments, and one or more clinical studies that include information on immunogenicity and pharmacokinetics (PK) or pharmacodynamics (PD) that is sufficient to demonstrate the safety, purity, and potency of the candidate biosimilar.

The FDA is also allowing manufacturers to submit data from animal studies and specified clinical studies comparing a proposed biosimilar product with a product not licensed in the United States, “as long as we are convinced that the reference product is equivalent to the U.S. product,” Dr. Woodcock said.

This “analytical bridge” process was requested by manufacturers who began development of biosimilars in Europe. The European Medicines Agency approved a biosimilar process in 2005, and gave the nod to the first biosimilar agents to existing erythropoietin products in 2007.

Current and pending

As of early October 2016, 66 programs were enrolled in FDA’s Biosimilar Product Development Program, and CDER has received requests for meetings with manufacturers to discuss what tests and documents are required for the development of biosimilars to 20 different reference products.

The FDA is prohibited from publicly discussing the existence of a pending application unless it has been previously disclosed or acknowledged publicly with the manufacturer’s permission, Dr. Woodcock noted, but as of Oct. 10, 2016, seven companies have announced a total of 10 biologic license applications for biosimilars to etanercept (Enbrel), adalimumab (Humira), pegfilgrastim (Neulasta), epoetin alfa (Epogen/Procrit), filgrastim (Neupogen), and infliximab (Remicade).

The FDA has granted licenses to four biosimilars to date (the four-letter suffix is intended to differentiate biosimilars agents from other biosimilars to the same reference product):

• Zarxio (filgrastim-sndz).
• Inflectra (infliximab-dyyb).
• Erelzi (etanercept-szzs).
• Amjevita (adalimumab-atto).

Physician perspective

“Everything I have heard suggests that biosimilars will be useful, but the scientist in me is a skeptic,” commented Donald Massenburg, MD, PhD, a rheumatologist at Wheaton Franciscan Healthcare in Franklin, Wisc., in an interview.

“I feel better now after learning that current biosimilars are not considered interchangeable, meaning that there can’t be substitutions made without the treating physician’s consent,” he said.

He acknowledged that “I wouldn’t be that excited” if a specific biosimilar was approved for interchangeability and was given to his patients without his knowledge.

Dr. Massenburg pointed to data from the NOR-SWITCH trial comparing the biosimilar Remsima to the reference product Remicade for treatment of rheumatic diseases, psoriasis, and inflammatory bowel disease. The trial showed that Remsima was noninferior to the reference product.

BOSTON – Biosimilar drugs are not identical twins of original biologic agents, but there are very strong family ties, and the newcomer is expected to look and behave very much like its older relative, said Janet Woodcock, MD, director of the Center for Drug Evaluation and Research at the Food and Drug Administration.

Although biosimilars differ from generic, small-molecule drugs, concerns about the development of biosimilars mirrors the kerfuffle over generic drugs surrounding the passage of the Hatch-Waxman (Drug Price Competition and Patent Term Restoration) Act in 1984.

• Are biosimilars as effective and as safe as the originally licensed biopharmaceuticals?
• If pharmacists substitute biosimilars for prescribed biologics, will patients be adversely affected?
• Can biosimilars reduce the high cost of biologic therapy?

“In certain specialties, this skepticism has persisted to this very day,” she said.

ACA mandate

Biosimilars owe their existence in large measure to the Biologics Price Competition and Innovation Act of 2009 (BPCI), passed as a part of the Affordable Care Act and signed into law by President Obama in 2010.

The act created an abbreviated licensure pathway for biologic products that can be shown to be either biosimilar to or interchangeable with an FDA-licensed reference drug.

A biosimilar is defined as a biological product that is highly similar to the reference product “notwithstanding minor differences in clinically inactive components,” and with no clinically meaningful differences between it and the reference product in terms of purity, safety, and potency.

To be interchangeable, a biosimilar must be expected to produce the same clinical results as the reference drug in any given patient, and “for a product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the product and its reference product is not greater than the risk of using the reference product without such alternation or switch.”

The definition of interchangeability includes the understanding that the prescriber’s approval is not necessary for substitution of a biosimilar for its reference product.

“If we’re going to have that kind of switching, if they are going to be interchangeable, then we have to have a very high bar,” Dr. Woodcock said.

She added that “any pressure people are feeling to push their patients to biosimilars is from the reimbursement system. There is no non-prescriber switching allowed currently; however, that doesn’t say there isn’t pressure on prescribers to write a different prescription.”

Faster track and bridge to approval

The biosimilar development and approval requires only convincing demonstration of biosimilarity to an existing agent, rather than an independent finding of safety or effectiveness, and the purpose of clinical studies in this case is to address “residual uncertainties,” Dr. Woodcock said.

Drug developers and regulatory authorities alike “are having trouble getting their mind around this concept,” she said.

The FDA requires manufacturers to provide data in their biosimilar drug license applications demonstrating biosimilarity based on analytical studies, animal studies that include toxicity assessments, and one or more clinical studies that include information on immunogenicity and pharmacokinetics (PK) or pharmacodynamics (PD) that is sufficient to demonstrate the safety, purity, and potency of the candidate biosimilar.

The FDA is also allowing manufacturers to submit data from animal studies and specified clinical studies comparing a proposed biosimilar product with a product not licensed in the United States, “as long as we are convinced that the reference product is equivalent to the U.S. product,” Dr. Woodcock said.

This “analytical bridge” process was requested by manufacturers who began development of biosimilars in Europe. The European Medicines Agency approved a biosimilar process in 2005, and gave the nod to the first biosimilar agents to existing erythropoietin products in 2007.

Current and pending

As of early October 2016, 66 programs were enrolled in FDA’s Biosimilar Product Development Program, and CDER has received requests for meetings with manufacturers to discuss what tests and documents are required for the development of biosimilars to 20 different reference products.

The FDA is prohibited from publicly discussing the existence of a pending application unless it has been previously disclosed or acknowledged publicly with the manufacturer’s permission, Dr. Woodcock noted, but as of Oct. 10, 2016, seven companies have announced a total of 10 biologic license applications for biosimilars to etanercept (Enbrel), adalimumab (Humira), pegfilgrastim (Neulasta), epoetin alfa (Epogen/Procrit), filgrastim (Neupogen), and infliximab (Remicade).

The FDA has granted licenses to four biosimilars to date (the four-letter suffix is intended to differentiate biosimilars agents from other biosimilars to the same reference product):

• Zarxio (filgrastim-sndz).
• Inflectra (infliximab-dyyb).
• Erelzi (etanercept-szzs).
• Amjevita (adalimumab-atto).

Physician perspective

“Everything I have heard suggests that biosimilars will be useful, but the scientist in me is a skeptic,” commented Donald Massenburg, MD, PhD, a rheumatologist at Wheaton Franciscan Healthcare in Franklin, Wisc., in an interview.

“I feel better now after learning that current biosimilars are not considered interchangeable, meaning that there can’t be substitutions made without the treating physician’s consent,” he said.

He acknowledged that “I wouldn’t be that excited” if a specific biosimilar was approved for interchangeability and was given to his patients without his knowledge.

Dr. Massenburg pointed to data from the NOR-SWITCH trial comparing the biosimilar Remsima to the reference product Remicade for treatment of rheumatic diseases, psoriasis, and inflammatory bowel disease. The trial showed that Remsima was noninferior to the reference product.

BOSTON – Biosimilar drugs are not identical twins of original biologic agents, but there are very strong family ties, and the newcomer is expected to look and behave very much like its older relative, said Janet Woodcock, MD, director of the Center for Drug Evaluation and Research at the Food and Drug Administration.

Although biosimilars differ from generic, small-molecule drugs, concerns about the development of biosimilars mirrors the kerfuffle over generic drugs surrounding the passage of the Hatch-Waxman (Drug Price Competition and Patent Term Restoration) Act in 1984.

• Are biosimilars as effective and as safe as the originally licensed biopharmaceuticals?
• If pharmacists substitute biosimilars for prescribed biologics, will patients be adversely affected?
• Can biosimilars reduce the high cost of biologic therapy?

“In certain specialties, this skepticism has persisted to this very day,” she said.

ACA mandate

Biosimilars owe their existence in large measure to the Biologics Price Competition and Innovation Act of 2009 (BPCI), passed as a part of the Affordable Care Act and signed into law by President Obama in 2010.

The act created an abbreviated licensure pathway for biologic products that can be shown to be either biosimilar to or interchangeable with an FDA-licensed reference drug.

A biosimilar is defined as a biological product that is highly similar to the reference product “notwithstanding minor differences in clinically inactive components,” and with no clinically meaningful differences between it and the reference product in terms of purity, safety, and potency.

To be interchangeable, a biosimilar must be expected to produce the same clinical results as the reference drug in any given patient, and “for a product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the product and its reference product is not greater than the risk of using the reference product without such alternation or switch.”

The definition of interchangeability includes the understanding that the prescriber’s approval is not necessary for substitution of a biosimilar for its reference product.

“If we’re going to have that kind of switching, if they are going to be interchangeable, then we have to have a very high bar,” Dr. Woodcock said.

She added that “any pressure people are feeling to push their patients to biosimilars is from the reimbursement system. There is no non-prescriber switching allowed currently; however, that doesn’t say there isn’t pressure on prescribers to write a different prescription.”

Faster track and bridge to approval

The biosimilar development and approval requires only convincing demonstration of biosimilarity to an existing agent, rather than an independent finding of safety or effectiveness, and the purpose of clinical studies in this case is to address “residual uncertainties,” Dr. Woodcock said.

Drug developers and regulatory authorities alike “are having trouble getting their mind around this concept,” she said.

The FDA requires manufacturers to provide data in their biosimilar drug license applications demonstrating biosimilarity based on analytical studies, animal studies that include toxicity assessments, and one or more clinical studies that include information on immunogenicity and pharmacokinetics (PK) or pharmacodynamics (PD) that is sufficient to demonstrate the safety, purity, and potency of the candidate biosimilar.

The FDA is also allowing manufacturers to submit data from animal studies and specified clinical studies comparing a proposed biosimilar product with a product not licensed in the United States, “as long as we are convinced that the reference product is equivalent to the U.S. product,” Dr. Woodcock said.

This “analytical bridge” process was requested by manufacturers who began development of biosimilars in Europe. The European Medicines Agency approved a biosimilar process in 2005, and gave the nod to the first biosimilar agents to existing erythropoietin products in 2007.

Current and pending

As of early October 2016, 66 programs were enrolled in FDA’s Biosimilar Product Development Program, and CDER has received requests for meetings with manufacturers to discuss what tests and documents are required for the development of biosimilars to 20 different reference products.

The FDA is prohibited from publicly discussing the existence of a pending application unless it has been previously disclosed or acknowledged publicly with the manufacturer’s permission, Dr. Woodcock noted, but as of Oct. 10, 2016, seven companies have announced a total of 10 biologic license applications for biosimilars to etanercept (Enbrel), adalimumab (Humira), pegfilgrastim (Neulasta), epoetin alfa (Epogen/Procrit), filgrastim (Neupogen), and infliximab (Remicade).

The FDA has granted licenses to four biosimilars to date (the four-letter suffix is intended to differentiate biosimilars agents from other biosimilars to the same reference product):

• Zarxio (filgrastim-sndz).
• Inflectra (infliximab-dyyb).
• Erelzi (etanercept-szzs).
• Amjevita (adalimumab-atto).

Physician perspective

“Everything I have heard suggests that biosimilars will be useful, but the scientist in me is a skeptic,” commented Donald Massenburg, MD, PhD, a rheumatologist at Wheaton Franciscan Healthcare in Franklin, Wisc., in an interview.

“I feel better now after learning that current biosimilars are not considered interchangeable, meaning that there can’t be substitutions made without the treating physician’s consent,” he said.

He acknowledged that “I wouldn’t be that excited” if a specific biosimilar was approved for interchangeability and was given to his patients without his knowledge.

Dr. Massenburg pointed to data from the NOR-SWITCH trial comparing the biosimilar Remsima to the reference product Remicade for treatment of rheumatic diseases, psoriasis, and inflammatory bowel disease. The trial showed that Remsima was noninferior to the reference product.

BOSTON – For rheumatologists, the primary selling points of biosimilar agents are their presumed efficacy and safety, and their promised cost savings, compared with the reference product, an original biologic agent.

But market forces, patient worries, and provider concerns threaten to file off at least some of biosimilars’ presumed competitive edge, says a rheumatologist involved in the development of biosimilars to treat rheumatic diseases.

“The availability of lower-priced biosimilars, if they’re truly lower priced, should decrease the cost of treating patients; if they’re not lower cost, then this advantage is not holding true,” said Jonathan Kay, MD, professor of medicine at UMass Memorial Medical Center in Worcester.

Misperceptions

A common concern among patients and uninformed providers is that biosimilars are the same as biomimics – cheap, usually foreign-made knockoffs of existing drugs that have not undergone regulatory scrutiny and may be neither effective nor safe.

“Biomimics scare patients and scare physicians,” he said, “and misunderstanding of the regulatory approval process, or lack of understanding of the regulatory review or approval process, also intimidates individuals about biosimilars.”

Acceptance of biosimilars is also hampered by a lack of long-term, real-world efficacy and safety data. This is due, in part, to the “inverted pyramid” nature of the biosimilar development and approval process, which starts with myriad analytical, chemical, and functional characterization studies; nonclinical studies; and pharmacokinetic and pharmacodynamic analyses, but only one or two clinical trials. In contrast, the development process for innovator biologics starts with molecular characterization, then moves through the traditional drug development stages of laboratory and preclinical studies, phase I and II trials, and finally phase III registration trials and post-marketing studies.

Because most of the drug development for biosimilars happens behind the scenes, patients and their physicians are often leery about the finished product, no matter how rigorously it was developed. Similarly, there is a paucity of data on long-term immunogenicity of biosimilars, Dr. Kay noted.

Extrapolating about extrapolation

The idea of extrapolation of indications for biosimilars is also an alien concept to many. Simply put, if a reference product is approved for rheumatoid arthritis and has additional indications for treatment of psoriatic arthritis, the approved biosimilar to the original can be extrapolated to be effective against the same indications, even if it has only been tested against one of the indications.

“We have a tremendous amount of clinical experience not only in randomized, controlled clinical trials but also years of marketing experience showing that the reference product is effective and safe for each of the indications for which it’s been approved, and knowing that the biosimilar is essentially like another [manufacturing] run of the reference product allows us to extrapolate indications. But until you become comfortable with accepting that concept, it is certainly a barrier to biosimilars,” he said.

Patients are also scared by the issue of interchangeability, which would allow pharmacists to substitute one product for another without approval of either the patient or the prescribing physician. However, there are currently no biosimilar agents approved as interchangeable by the Food and Drug Administration.

What cost savings?

In the United States, the price of marketed biosimilars has been only 15% lower than that of the reference product, Dr. Kay noted, and multiple discount programs and rebates offered by marketers of the reference product make it difficult to figure out the actual costs of the drugs to payers and whether biosimilars are actually any cheaper.

Additionally, clinicians may be reluctant to adopt biosimilars because of a Centers for Medicare & Medicaid Services billing quirk that currently offers only a single “J” code with a blended reimbursement for all biosimilar agents of a reference product, regardless of cost differences.

Nordic competition model

Dr. Kay pointed to the Norwegian Tender System as a model for using biosimilars to drive down drug costs.

The Norwegian Drug Procurement Cooperation (LIS) annually procures drugs for all publicly funded hospitals, which ensures that prices offered to hospitals for patent-protected medicines are lower than those offered for distribution to wholesalers or pharmacies. Under this system, cost is the driving factor, assuming that drugs in a similar class have similar efficacy and safety, he said.

In 2015, when Norway was purchasing infliximab, it chose Remsima, the biosimilar, over the reference product Remicade, resulting in a 69% cost saving.

The potential interchangeability of Remsima and Remicade in patients with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn’s disease, and chronic plaque psoriasis is currently being explored in the NOR-SWITCH trial.

Dr. Kay disclosed receiving institutional grants from AbbVie, Genentech, Roche Laboratories, and UCB, and serving as a consultant for those companies.

BOSTON – For rheumatologists, the primary selling points of biosimilar agents are their presumed efficacy and safety, and their promised cost savings, compared with the reference product, an original biologic agent.

But market forces, patient worries, and provider concerns threaten to file off at least some of biosimilars’ presumed competitive edge, says a rheumatologist involved in the development of biosimilars to treat rheumatic diseases.

“The availability of lower-priced biosimilars, if they’re truly lower priced, should decrease the cost of treating patients; if they’re not lower cost, then this advantage is not holding true,” said Jonathan Kay, MD, professor of medicine at UMass Memorial Medical Center in Worcester.

Misperceptions

A common concern among patients and uninformed providers is that biosimilars are the same as biomimics – cheap, usually foreign-made knockoffs of existing drugs that have not undergone regulatory scrutiny and may be neither effective nor safe.

“Biomimics scare patients and scare physicians,” he said, “and misunderstanding of the regulatory approval process, or lack of understanding of the regulatory review or approval process, also intimidates individuals about biosimilars.”

Acceptance of biosimilars is also hampered by a lack of long-term, real-world efficacy and safety data. This is due, in part, to the “inverted pyramid” nature of the biosimilar development and approval process, which starts with myriad analytical, chemical, and functional characterization studies; nonclinical studies; and pharmacokinetic and pharmacodynamic analyses, but only one or two clinical trials. In contrast, the development process for innovator biologics starts with molecular characterization, then moves through the traditional drug development stages of laboratory and preclinical studies, phase I and II trials, and finally phase III registration trials and post-marketing studies.

Because most of the drug development for biosimilars happens behind the scenes, patients and their physicians are often leery about the finished product, no matter how rigorously it was developed. Similarly, there is a paucity of data on long-term immunogenicity of biosimilars, Dr. Kay noted.

Extrapolating about extrapolation

The idea of extrapolation of indications for biosimilars is also an alien concept to many. Simply put, if a reference product is approved for rheumatoid arthritis and has additional indications for treatment of psoriatic arthritis, the approved biosimilar to the original can be extrapolated to be effective against the same indications, even if it has only been tested against one of the indications.

“We have a tremendous amount of clinical experience not only in randomized, controlled clinical trials but also years of marketing experience showing that the reference product is effective and safe for each of the indications for which it’s been approved, and knowing that the biosimilar is essentially like another [manufacturing] run of the reference product allows us to extrapolate indications. But until you become comfortable with accepting that concept, it is certainly a barrier to biosimilars,” he said.

Patients are also scared by the issue of interchangeability, which would allow pharmacists to substitute one product for another without approval of either the patient or the prescribing physician. However, there are currently no biosimilar agents approved as interchangeable by the Food and Drug Administration.

What cost savings?

In the United States, the price of marketed biosimilars has been only 15% lower than that of the reference product, Dr. Kay noted, and multiple discount programs and rebates offered by marketers of the reference product make it difficult to figure out the actual costs of the drugs to payers and whether biosimilars are actually any cheaper.

Additionally, clinicians may be reluctant to adopt biosimilars because of a Centers for Medicare & Medicaid Services billing quirk that currently offers only a single “J” code with a blended reimbursement for all biosimilar agents of a reference product, regardless of cost differences.

Nordic competition model

Dr. Kay pointed to the Norwegian Tender System as a model for using biosimilars to drive down drug costs.

The Norwegian Drug Procurement Cooperation (LIS) annually procures drugs for all publicly funded hospitals, which ensures that prices offered to hospitals for patent-protected medicines are lower than those offered for distribution to wholesalers or pharmacies. Under this system, cost is the driving factor, assuming that drugs in a similar class have similar efficacy and safety, he said.

In 2015, when Norway was purchasing infliximab, it chose Remsima, the biosimilar, over the reference product Remicade, resulting in a 69% cost saving.

The potential interchangeability of Remsima and Remicade in patients with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn’s disease, and chronic plaque psoriasis is currently being explored in the NOR-SWITCH trial.

Dr. Kay disclosed receiving institutional grants from AbbVie, Genentech, Roche Laboratories, and UCB, and serving as a consultant for those companies.

BOSTON – For rheumatologists, the primary selling points of biosimilar agents are their presumed efficacy and safety, and their promised cost savings, compared with the reference product, an original biologic agent.

But market forces, patient worries, and provider concerns threaten to file off at least some of biosimilars’ presumed competitive edge, says a rheumatologist involved in the development of biosimilars to treat rheumatic diseases.

“The availability of lower-priced biosimilars, if they’re truly lower priced, should decrease the cost of treating patients; if they’re not lower cost, then this advantage is not holding true,” said Jonathan Kay, MD, professor of medicine at UMass Memorial Medical Center in Worcester.

Misperceptions

A common concern among patients and uninformed providers is that biosimilars are the same as biomimics – cheap, usually foreign-made knockoffs of existing drugs that have not undergone regulatory scrutiny and may be neither effective nor safe.

“Biomimics scare patients and scare physicians,” he said, “and misunderstanding of the regulatory approval process, or lack of understanding of the regulatory review or approval process, also intimidates individuals about biosimilars.”

Acceptance of biosimilars is also hampered by a lack of long-term, real-world efficacy and safety data. This is due, in part, to the “inverted pyramid” nature of the biosimilar development and approval process, which starts with myriad analytical, chemical, and functional characterization studies; nonclinical studies; and pharmacokinetic and pharmacodynamic analyses, but only one or two clinical trials. In contrast, the development process for innovator biologics starts with molecular characterization, then moves through the traditional drug development stages of laboratory and preclinical studies, phase I and II trials, and finally phase III registration trials and post-marketing studies.

Because most of the drug development for biosimilars happens behind the scenes, patients and their physicians are often leery about the finished product, no matter how rigorously it was developed. Similarly, there is a paucity of data on long-term immunogenicity of biosimilars, Dr. Kay noted.

Extrapolating about extrapolation

The idea of extrapolation of indications for biosimilars is also an alien concept to many. Simply put, if a reference product is approved for rheumatoid arthritis and has additional indications for treatment of psoriatic arthritis, the approved biosimilar to the original can be extrapolated to be effective against the same indications, even if it has only been tested against one of the indications.

“We have a tremendous amount of clinical experience not only in randomized, controlled clinical trials but also years of marketing experience showing that the reference product is effective and safe for each of the indications for which it’s been approved, and knowing that the biosimilar is essentially like another [manufacturing] run of the reference product allows us to extrapolate indications. But until you become comfortable with accepting that concept, it is certainly a barrier to biosimilars,” he said.

Patients are also scared by the issue of interchangeability, which would allow pharmacists to substitute one product for another without approval of either the patient or the prescribing physician. However, there are currently no biosimilar agents approved as interchangeable by the Food and Drug Administration.

What cost savings?

In the United States, the price of marketed biosimilars has been only 15% lower than that of the reference product, Dr. Kay noted, and multiple discount programs and rebates offered by marketers of the reference product make it difficult to figure out the actual costs of the drugs to payers and whether biosimilars are actually any cheaper.

Additionally, clinicians may be reluctant to adopt biosimilars because of a Centers for Medicare & Medicaid Services billing quirk that currently offers only a single “J” code with a blended reimbursement for all biosimilar agents of a reference product, regardless of cost differences.

Nordic competition model

Dr. Kay pointed to the Norwegian Tender System as a model for using biosimilars to drive down drug costs.

The Norwegian Drug Procurement Cooperation (LIS) annually procures drugs for all publicly funded hospitals, which ensures that prices offered to hospitals for patent-protected medicines are lower than those offered for distribution to wholesalers or pharmacies. Under this system, cost is the driving factor, assuming that drugs in a similar class have similar efficacy and safety, he said.

In 2015, when Norway was purchasing infliximab, it chose Remsima, the biosimilar, over the reference product Remicade, resulting in a 69% cost saving.

The potential interchangeability of Remsima and Remicade in patients with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn’s disease, and chronic plaque psoriasis is currently being explored in the NOR-SWITCH trial.

Dr. Kay disclosed receiving institutional grants from AbbVie, Genentech, Roche Laboratories, and UCB, and serving as a consultant for those companies.

Intravitreal sirolimus 440 mcg or 880 mcg administered on days 1, 60, and 120, was shown to significantly improve ocular inflammation with preservation of best-corrected visual acuity in patients with noninfectious uveitis of the posterior segment, a phase III study has shown.

In the multinational SAKURA (Study Assessing Double-masked Uveitis Treatment) study, 346 study eyes were analyzed in this randomly assigned, double-masked, actively controlled study. In the study arm given intravitreal sirolimus 440 mcg, 22.8% (P = .025) met the primary endpoint of no vitreous haze (VH) at month 5 in the study eye without the aid of rescue therapy. In the group given intravitreal sirolimus 880 mcg, 16.4% (P = .182) met the primary endpoint, compared with 10.3% of active controls who were given 44 mcg intravitreal sirolimus.

For the secondary outcome, 52.6% (P = .008) of the intravitreal sirolimus 440 mcg arm had VH scores of 0 or a 0.5+ response rate at month 5. In the intravitreal sirolimus 880 mcg, 43.1% (P = .228) achieved a VH score of 0 or a 0.5+ response rate, compared with 35% of the 44 mcg active control group. Mean best-corrected visual acuity was maintained throughout the study in each study arm, with 76.9% of those who received corticosteroids at baseline in the 440 mcg study arm successfully tapering them to 5 mg per day or less by month 5, and 66.7% of those receiving corticosteroids in the 880 mcg group doing so. This was in comparison with 63.6% of those using corticosteroids in the active control group. Adverse events were similar across the study, and all doses were well tolerated. The study was funded by Santen.

Read the full study in Ophthalmology (2016;23[11]:2413-23).
 

[email protected]

On Twitter @whitneymcknight

Intravitreal sirolimus 440 mcg or 880 mcg administered on days 1, 60, and 120, was shown to significantly improve ocular inflammation with preservation of best-corrected visual acuity in patients with noninfectious uveitis of the posterior segment, a phase III study has shown.

In the multinational SAKURA (Study Assessing Double-masked Uveitis Treatment) study, 346 study eyes were analyzed in this randomly assigned, double-masked, actively controlled study. In the study arm given intravitreal sirolimus 440 mcg, 22.8% (P = .025) met the primary endpoint of no vitreous haze (VH) at month 5 in the study eye without the aid of rescue therapy. In the group given intravitreal sirolimus 880 mcg, 16.4% (P = .182) met the primary endpoint, compared with 10.3% of active controls who were given 44 mcg intravitreal sirolimus.

For the secondary outcome, 52.6% (P = .008) of the intravitreal sirolimus 440 mcg arm had VH scores of 0 or a 0.5+ response rate at month 5. In the intravitreal sirolimus 880 mcg, 43.1% (P = .228) achieved a VH score of 0 or a 0.5+ response rate, compared with 35% of the 44 mcg active control group. Mean best-corrected visual acuity was maintained throughout the study in each study arm, with 76.9% of those who received corticosteroids at baseline in the 440 mcg study arm successfully tapering them to 5 mg per day or less by month 5, and 66.7% of those receiving corticosteroids in the 880 mcg group doing so. This was in comparison with 63.6% of those using corticosteroids in the active control group. Adverse events were similar across the study, and all doses were well tolerated. The study was funded by Santen.

Read the full study in Ophthalmology (2016;23[11]:2413-23).
 

[email protected]

On Twitter @whitneymcknight

Intravitreal sirolimus 440 mcg or 880 mcg administered on days 1, 60, and 120, was shown to significantly improve ocular inflammation with preservation of best-corrected visual acuity in patients with noninfectious uveitis of the posterior segment, a phase III study has shown.

In the multinational SAKURA (Study Assessing Double-masked Uveitis Treatment) study, 346 study eyes were analyzed in this randomly assigned, double-masked, actively controlled study. In the study arm given intravitreal sirolimus 440 mcg, 22.8% (P = .025) met the primary endpoint of no vitreous haze (VH) at month 5 in the study eye without the aid of rescue therapy. In the group given intravitreal sirolimus 880 mcg, 16.4% (P = .182) met the primary endpoint, compared with 10.3% of active controls who were given 44 mcg intravitreal sirolimus.

For the secondary outcome, 52.6% (P = .008) of the intravitreal sirolimus 440 mcg arm had VH scores of 0 or a 0.5+ response rate at month 5. In the intravitreal sirolimus 880 mcg, 43.1% (P = .228) achieved a VH score of 0 or a 0.5+ response rate, compared with 35% of the 44 mcg active control group. Mean best-corrected visual acuity was maintained throughout the study in each study arm, with 76.9% of those who received corticosteroids at baseline in the 440 mcg study arm successfully tapering them to 5 mg per day or less by month 5, and 66.7% of those receiving corticosteroids in the 880 mcg group doing so. This was in comparison with 63.6% of those using corticosteroids in the active control group. Adverse events were similar across the study, and all doses were well tolerated. The study was funded by Santen.

Read the full study in Ophthalmology (2016;23[11]:2413-23).
 

[email protected]

On Twitter @whitneymcknight