Spondyloarthropathies

A new study has determined modifiable and nonmodifiable factors that can help identify patients with axial spondyloarthritis who are both likely and unlikely to respond to anti–tumor necrosis factor (TNF)–alpha therapy.

Courtesy Dr. Gary J. Macfarlane

“[This study] emphasizes that examination of predictors of nonresponse to pharmacologic therapy in inflammatory arthritis must consider the importance of socioeconomic factors,” wrote Gary J. Macfarlane, MBChB, PhD, of the University of Aberdeen (Scotland) and coauthors. The study was published in Rheumatology.

To identify common factors related to anti–TNF-alpha therapy response, the researchers launched a prospective cohort study of 335 patients with axial spondyloarthritis from the British Society for Rheumatology Biologics Register in Axial Spondyloarthritis (BSRBR-AS) who were naive to biologic therapy. Responses to therapy were assessed through various means, including meeting Assessment of Spondyloarthritis International Society (ASAS) improvement criteria, exhibiting clinically important improvement (1.1 points or more) in Ankylosing Spondylitis Disease Activity Score (ASDAS), or going from a high or very high ASDAS disease state (score of 2.1 or higher) to a moderate or inactive state (score less than 2.1).

All patients also filled out questionnaires at each follow-up on socioeconomic factors, lifestyle factors, and quality of life. Of the 335 participants, 69% were male. They had a median age of 47 years, and about half were employed full time.

At first follow-up – which occurred at a median of 14 weeks – 175 participants (52%) met ASAS20 response criteria and 111 (33%) met ASAS40 response criteria. Of the 261 participants eligible for ASDAS evaluation, 122 (47%) met the criteria for a clinically important ASDAS reduction. Of the 249 participants who had a high or very high disease state at baseline, 87 (35%) were classified as having moderate or inactive disease at follow-up.

Factors that predicted a lack of response across measures included adverse socioeconomic factors, fewer years of education, and not working full time. Clinical and patient-reported factors also associated with a lack of response included comorbidities and poor mental health. The ASDAS models proved best at predicting those unlikely to meet response criteria, with a negative predictive value of 77%.

The study was supported by the British Society for Rheumatology, which receives funding for the BSRBR-AS from Pfizer, AbbVie, and UCB. The authors reported having no conflicts of interest.

SOURCE: Macfarlane GJ et al. Rheumatology. 2020 Jan 28. doi: 10.1093/rheumatology/kez657.

A new study has determined modifiable and nonmodifiable factors that can help identify patients with axial spondyloarthritis who are both likely and unlikely to respond to anti–tumor necrosis factor (TNF)–alpha therapy.

Courtesy Dr. Gary J. Macfarlane

“[This study] emphasizes that examination of predictors of nonresponse to pharmacologic therapy in inflammatory arthritis must consider the importance of socioeconomic factors,” wrote Gary J. Macfarlane, MBChB, PhD, of the University of Aberdeen (Scotland) and coauthors. The study was published in Rheumatology.

To identify common factors related to anti–TNF-alpha therapy response, the researchers launched a prospective cohort study of 335 patients with axial spondyloarthritis from the British Society for Rheumatology Biologics Register in Axial Spondyloarthritis (BSRBR-AS) who were naive to biologic therapy. Responses to therapy were assessed through various means, including meeting Assessment of Spondyloarthritis International Society (ASAS) improvement criteria, exhibiting clinically important improvement (1.1 points or more) in Ankylosing Spondylitis Disease Activity Score (ASDAS), or going from a high or very high ASDAS disease state (score of 2.1 or higher) to a moderate or inactive state (score less than 2.1).

All patients also filled out questionnaires at each follow-up on socioeconomic factors, lifestyle factors, and quality of life. Of the 335 participants, 69% were male. They had a median age of 47 years, and about half were employed full time.

At first follow-up – which occurred at a median of 14 weeks – 175 participants (52%) met ASAS20 response criteria and 111 (33%) met ASAS40 response criteria. Of the 261 participants eligible for ASDAS evaluation, 122 (47%) met the criteria for a clinically important ASDAS reduction. Of the 249 participants who had a high or very high disease state at baseline, 87 (35%) were classified as having moderate or inactive disease at follow-up.

Factors that predicted a lack of response across measures included adverse socioeconomic factors, fewer years of education, and not working full time. Clinical and patient-reported factors also associated with a lack of response included comorbidities and poor mental health. The ASDAS models proved best at predicting those unlikely to meet response criteria, with a negative predictive value of 77%.

The study was supported by the British Society for Rheumatology, which receives funding for the BSRBR-AS from Pfizer, AbbVie, and UCB. The authors reported having no conflicts of interest.

SOURCE: Macfarlane GJ et al. Rheumatology. 2020 Jan 28. doi: 10.1093/rheumatology/kez657.

A new study has determined modifiable and nonmodifiable factors that can help identify patients with axial spondyloarthritis who are both likely and unlikely to respond to anti–tumor necrosis factor (TNF)–alpha therapy.

Courtesy Dr. Gary J. Macfarlane

“[This study] emphasizes that examination of predictors of nonresponse to pharmacologic therapy in inflammatory arthritis must consider the importance of socioeconomic factors,” wrote Gary J. Macfarlane, MBChB, PhD, of the University of Aberdeen (Scotland) and coauthors. The study was published in Rheumatology.

To identify common factors related to anti–TNF-alpha therapy response, the researchers launched a prospective cohort study of 335 patients with axial spondyloarthritis from the British Society for Rheumatology Biologics Register in Axial Spondyloarthritis (BSRBR-AS) who were naive to biologic therapy. Responses to therapy were assessed through various means, including meeting Assessment of Spondyloarthritis International Society (ASAS) improvement criteria, exhibiting clinically important improvement (1.1 points or more) in Ankylosing Spondylitis Disease Activity Score (ASDAS), or going from a high or very high ASDAS disease state (score of 2.1 or higher) to a moderate or inactive state (score less than 2.1).

All patients also filled out questionnaires at each follow-up on socioeconomic factors, lifestyle factors, and quality of life. Of the 335 participants, 69% were male. They had a median age of 47 years, and about half were employed full time.

At first follow-up – which occurred at a median of 14 weeks – 175 participants (52%) met ASAS20 response criteria and 111 (33%) met ASAS40 response criteria. Of the 261 participants eligible for ASDAS evaluation, 122 (47%) met the criteria for a clinically important ASDAS reduction. Of the 249 participants who had a high or very high disease state at baseline, 87 (35%) were classified as having moderate or inactive disease at follow-up.

Factors that predicted a lack of response across measures included adverse socioeconomic factors, fewer years of education, and not working full time. Clinical and patient-reported factors also associated with a lack of response included comorbidities and poor mental health. The ASDAS models proved best at predicting those unlikely to meet response criteria, with a negative predictive value of 77%.

The study was supported by the British Society for Rheumatology, which receives funding for the BSRBR-AS from Pfizer, AbbVie, and UCB. The authors reported having no conflicts of interest.

SOURCE: Macfarlane GJ et al. Rheumatology. 2020 Jan 28. doi: 10.1093/rheumatology/kez657.

Although biosimilar versions of tumor necrosis factor inhibitors (TNFis) have been available to U.S. rheumatologists and their patients for over 3 years, uptake has thus far been slow.

monkeybusinessimages/thinkstockphotos.com

In an analysis of data from a large commercial payer, the two available biosimilars for infliximab (Remicade) accounted for less than 1% of TNFi prescribing since the first biosimilar to infliximab was approved in 2016.

The study, published in Arthritis & Rheumatology, involved a total of 1.1 million TNFi prescriptions or infusions received by 95,906 patients from 2016 to 2019. Investigators found that uptake of biosimilar infliximab was essentially flat, standing at 0.1% of prescribing in the second quarter of 2017, and topping out at 0.9% in the first quarter of 2019. For branded infliximab, prescribing was also stable, but accounted for about 20% of overall biologic dispensing in each quarter of the period studied.

There are currently two biosimilar medications to the originator infliximab, which is one of five originator biologics available to treat rheumatic diseases in the United States: infliximab-dyyb (Inflectra) and infliximab-abda (Renflexis). The former was approved in 2016 and the latter in 2017, said study author Seoyoung C. Kim, MD, ScD, of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston, and her coauthors.

“Our paper reports a disappointingly low uptake of biosimilar infliximab since the first quarter of 2017 using claims data from a large private health plan. The main and maybe the only reason to consider using a biosimilar is cost saving,” said Dr. Kim in an interview. “Our results suggest that current modest cost savings from infliximab biosimilars in the U.S. are not sufficient to promote their widespread use.”

In the payer database study conducted by Dr. Kim and colleagues, the insurer paid similar mean amounts per patient per quarter for originator and biosimilar infliximab in mid-2017 ($8,322 versus $8,656). By the end of 2018, a gap appeared, with the insurer paying a mean quarterly per-patient sum of $8,111 for biosimilar infliximab compared with $9,535 for the branded biologic.

“The lack of market penetration and very modest price reductions for biosimilars have left policymakers, payers, physicians, and the public frustrated, particularly because sales in Europe continue to rapidly expand and robust cost-savings have materialized,” wrote Jinoos Yazdany, MD, MPH, in an editorial accompanying the study.

Dr. Yazdany, professor and chief of the division of rheumatology at the University of California, San Francisco, noted that increased spending on biologics in the United States – which increased by 50% from 2014 to 2018 – has been driven by rising prices as well as increased uptake of biologic therapies.

At least in part, Europe has been able to reap cost savings where the United States hasn’t because fundamental differences in health care reimbursement can ease sweeping biosimilar adoption, Dr. Yazdany noted. “Countries like Denmark and Sweden, using the negotiating and purchasing power of their single-payer systems have instituted a winner-takes-all bidding system,” with Denmark seeing cost savings of up to two-thirds when bidding was combined with mandatory switching, she said.

The continued market dominance of originator infliximab means that savings from biosimilars have thus far amounted to about $91 million, far short of the $1 billion that the Congressional Budget Office had projected for this date, Dr. Yazdany said.

One problem in the adoption of biosimilars by U.S. rheumatologists may have been uneven marketing and pricing across different types of practice, Colin C. Edgerton, MD, a rheumatologist at Low Country Rheumatology in South Carolina and chair of the American College of Rheumatology’s Committee on Rheumatologic Care, said in an interview.

“Rheumatologists have generally developed comfort with biosimilars, although this is not universal. The core message, that all biologics vary and that this is OK, is getting out. In general, rheumatologists also understand the problem with high drug prices and the threat to patient access,” Dr. Edgerton said. But “the early marketing and pricing focus for biosimilars seemed to be on hospitals and facilities, and this did not work effectively for community rheumatologists, where the majority of care is delivered. We have been pleased to see a manufacturer pivot toward community rheumatology where additional efforts need to be made to bend the curve on biosimilar adoption. It is critical for practices with experience using biosimilars to educate peers, and this is where networks of practicing rheumatologists are important.”

In Dr. Yazdany’s editorial, she cited four structural factors impeding biosimilar uptake and downstream savings.

First, she cites ongoing actions by pharmaceutical companies, which create a “patent thicket” that has the effect of fencing off originator biologics from biosimilars long beyond the original 12-year exclusivity period. Supporting the notion that “patent thickets” are a common strategy, Dr. Yazdany noted that almost half of the patent applications that AbbVie has filed for adalimumab (Humira) have come in after the original exclusivity period expired in 2014. Humira’s price has risen 18% yearly during this period.

The complicated role played by pharmacy benefit managers (PBMs) is another factor in slow adoption, said Dr. Yazdany: When manufacturers offer rebates to PBMs, the price of the originator biologic may be less than its biosimilar. Further, manufacturers may sign multiyear rebate agreements just before a biosimilar launch; PBMs are also sometimes threatened with the withdrawal of rebates if they offer biosimilars, she noted.

Third, prescriber inertia may also be at play, Dr. Yazdany noted, not least because patients often see little difference in out-of-pocket costs when they make the switch to a biosimilar – PBM rebates are not necessarily passed on to patients. Payers may not reimburse a biosimilar, or formularies can be built without them, influencing prescribing, and there’s usually no reimbursement incentive for biosimilar prescribing in the nonpublic sector, she said. To the contrary, infusing a drug with a higher price often means higher reimbursement for the administering clinician, since commercial insurance reimbursement is often calculated as a percent of the charge for the drug.

Further contributing to inertia is the extra time required for patient education and writing a new set of orders – all work that can’t be captured for extra reimbursement. Dr. Edgerton said that rheumatologists can talk with patients about the “nocebo effect” relating to biosimilars. “This is a phenomenon in which patients are thought to experience worsening symptoms associated with negative beliefs about biosimilars. There has been a study in Arthritis Care & Research addressing this concern. The authors found that positive framing of biosimilars led to more participants being willing to switch than negative framing. This suggests that clinicians have an important role in informing patients about biosimilars, and addressing hesitancy.”

Finally, Dr. Yazdany pointed out that for a pharmaceutical company pursuing biosimilar approval, the regulatory pathway itself can provide its own set of complications and confusion. Biosimilars are not exact molecular replicas of the originator biologic, and these differences can change efficacy and immunogenicity, and also affect stability. Hence, a company wishing to market a biosimilar has to show the Food and Drug Administration that safety and efficacy aren’t affected by a switch to biosimilar from an originator biologic. Extrapolation from one indication to another can be made – with scientific justification.

Rheumatologists are mindful of the potential differences between biosimilars and the originator biologic, as evinced in a recent position statement from the American College of Rheumatology. The position statement advises that “extrapolation should be pursued with caution,” and asks for clear labeling when biosimilars have been designated “interchangeable” with their biosimilar. Interchangeability can clear the way for pharmacy substitution of a prescribed biologic, though Dr. Yazdany noted that 40 states have passed legislation requiring prescriber notification.

The FDA is currently using postmarketing pharmacovigilance to monitor biosimilar performance in the real world, and a recent systematic review “should provide some reassurance,” wrote Dr. Yazdany, citing the study, which looked at 14,000 patients who had a total of 14 disease indications for biosimilar use. The 90-article review largely found no differences in safety, efficacy, or immunogenicity between originators and their biosimilars. Dr. Yazdany recommended greater openness to incorporating the European experience in the FDA’s ongoing reassessment.

A further way forward can come through tackling the patent thicket with the proposed bipartisan Biologic Patent Transparency Act, which would require publication of biologic patents in a one-stop publicly searchable database. Going further with legislation to address anticompetitive activity by pharmaceutical companies could shorten the runway to biosimilar launching considerably, she noted.

The complicated landscape of PBMs and rebates affects many sectors of health care, and new policy efforts are needed here as well, she said. Reimbursement strategies – and much-needed continuing medical education – can both ease prescriber unfamiliarity with biosimilars and provide incentives for their use, she concluded.

Dr. Kim concurred that change is needed before the United States is likely to reap significant economic benefit from biosimilars. “The uptake of biosimilars and their impact on overall health care cost needs to be reevaluated when we have more biosimilars available in the next 3-4 years. However, for now, it appears that substantial savings achieved in some European countries – for example, Denmark – may not be possible without systemic reform of the U.S. pharmaceutical market,” she said.

Dr. Yazdany is supported by the Alice Betts Endowed Chair in Arthritis Research, the Russel/Engleman Research Center at the University of California, San Francisco, and the National Institutes of Health. She has received independent research grants from Pfizer and Genentech and research consulting fees from Eli Lilly and AstraZeneca.

Dr. Kim’s study was supported by the division of pharmacoepidemiology and pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Arnold Ventures. Dr. Kim has received research grants to Brigham and Women’s Hospital from Pfizer, AbbVie, Bristol-Myers Squibb, and Roche.

[email protected]

SOURCES: Kim SC et al. Arthritis Rheumatol. 2020 Jan 13. doi: 10.1002/art.41201; Yazdany J. Arthritis Rheumatol. 2020 Jan 10. doi: 10.1002/art.41203.

Although biosimilar versions of tumor necrosis factor inhibitors (TNFis) have been available to U.S. rheumatologists and their patients for over 3 years, uptake has thus far been slow.

monkeybusinessimages/thinkstockphotos.com

In an analysis of data from a large commercial payer, the two available biosimilars for infliximab (Remicade) accounted for less than 1% of TNFi prescribing since the first biosimilar to infliximab was approved in 2016.

The study, published in Arthritis & Rheumatology, involved a total of 1.1 million TNFi prescriptions or infusions received by 95,906 patients from 2016 to 2019. Investigators found that uptake of biosimilar infliximab was essentially flat, standing at 0.1% of prescribing in the second quarter of 2017, and topping out at 0.9% in the first quarter of 2019. For branded infliximab, prescribing was also stable, but accounted for about 20% of overall biologic dispensing in each quarter of the period studied.

There are currently two biosimilar medications to the originator infliximab, which is one of five originator biologics available to treat rheumatic diseases in the United States: infliximab-dyyb (Inflectra) and infliximab-abda (Renflexis). The former was approved in 2016 and the latter in 2017, said study author Seoyoung C. Kim, MD, ScD, of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston, and her coauthors.

“Our paper reports a disappointingly low uptake of biosimilar infliximab since the first quarter of 2017 using claims data from a large private health plan. The main and maybe the only reason to consider using a biosimilar is cost saving,” said Dr. Kim in an interview. “Our results suggest that current modest cost savings from infliximab biosimilars in the U.S. are not sufficient to promote their widespread use.”

In the payer database study conducted by Dr. Kim and colleagues, the insurer paid similar mean amounts per patient per quarter for originator and biosimilar infliximab in mid-2017 ($8,322 versus $8,656). By the end of 2018, a gap appeared, with the insurer paying a mean quarterly per-patient sum of $8,111 for biosimilar infliximab compared with $9,535 for the branded biologic.

“The lack of market penetration and very modest price reductions for biosimilars have left policymakers, payers, physicians, and the public frustrated, particularly because sales in Europe continue to rapidly expand and robust cost-savings have materialized,” wrote Jinoos Yazdany, MD, MPH, in an editorial accompanying the study.

Dr. Yazdany, professor and chief of the division of rheumatology at the University of California, San Francisco, noted that increased spending on biologics in the United States – which increased by 50% from 2014 to 2018 – has been driven by rising prices as well as increased uptake of biologic therapies.

At least in part, Europe has been able to reap cost savings where the United States hasn’t because fundamental differences in health care reimbursement can ease sweeping biosimilar adoption, Dr. Yazdany noted. “Countries like Denmark and Sweden, using the negotiating and purchasing power of their single-payer systems have instituted a winner-takes-all bidding system,” with Denmark seeing cost savings of up to two-thirds when bidding was combined with mandatory switching, she said.

The continued market dominance of originator infliximab means that savings from biosimilars have thus far amounted to about $91 million, far short of the $1 billion that the Congressional Budget Office had projected for this date, Dr. Yazdany said.

One problem in the adoption of biosimilars by U.S. rheumatologists may have been uneven marketing and pricing across different types of practice, Colin C. Edgerton, MD, a rheumatologist at Low Country Rheumatology in South Carolina and chair of the American College of Rheumatology’s Committee on Rheumatologic Care, said in an interview.

“Rheumatologists have generally developed comfort with biosimilars, although this is not universal. The core message, that all biologics vary and that this is OK, is getting out. In general, rheumatologists also understand the problem with high drug prices and the threat to patient access,” Dr. Edgerton said. But “the early marketing and pricing focus for biosimilars seemed to be on hospitals and facilities, and this did not work effectively for community rheumatologists, where the majority of care is delivered. We have been pleased to see a manufacturer pivot toward community rheumatology where additional efforts need to be made to bend the curve on biosimilar adoption. It is critical for practices with experience using biosimilars to educate peers, and this is where networks of practicing rheumatologists are important.”

In Dr. Yazdany’s editorial, she cited four structural factors impeding biosimilar uptake and downstream savings.

First, she cites ongoing actions by pharmaceutical companies, which create a “patent thicket” that has the effect of fencing off originator biologics from biosimilars long beyond the original 12-year exclusivity period. Supporting the notion that “patent thickets” are a common strategy, Dr. Yazdany noted that almost half of the patent applications that AbbVie has filed for adalimumab (Humira) have come in after the original exclusivity period expired in 2014. Humira’s price has risen 18% yearly during this period.

The complicated role played by pharmacy benefit managers (PBMs) is another factor in slow adoption, said Dr. Yazdany: When manufacturers offer rebates to PBMs, the price of the originator biologic may be less than its biosimilar. Further, manufacturers may sign multiyear rebate agreements just before a biosimilar launch; PBMs are also sometimes threatened with the withdrawal of rebates if they offer biosimilars, she noted.

Third, prescriber inertia may also be at play, Dr. Yazdany noted, not least because patients often see little difference in out-of-pocket costs when they make the switch to a biosimilar – PBM rebates are not necessarily passed on to patients. Payers may not reimburse a biosimilar, or formularies can be built without them, influencing prescribing, and there’s usually no reimbursement incentive for biosimilar prescribing in the nonpublic sector, she said. To the contrary, infusing a drug with a higher price often means higher reimbursement for the administering clinician, since commercial insurance reimbursement is often calculated as a percent of the charge for the drug.

Further contributing to inertia is the extra time required for patient education and writing a new set of orders – all work that can’t be captured for extra reimbursement. Dr. Edgerton said that rheumatologists can talk with patients about the “nocebo effect” relating to biosimilars. “This is a phenomenon in which patients are thought to experience worsening symptoms associated with negative beliefs about biosimilars. There has been a study in Arthritis Care & Research addressing this concern. The authors found that positive framing of biosimilars led to more participants being willing to switch than negative framing. This suggests that clinicians have an important role in informing patients about biosimilars, and addressing hesitancy.”

Finally, Dr. Yazdany pointed out that for a pharmaceutical company pursuing biosimilar approval, the regulatory pathway itself can provide its own set of complications and confusion. Biosimilars are not exact molecular replicas of the originator biologic, and these differences can change efficacy and immunogenicity, and also affect stability. Hence, a company wishing to market a biosimilar has to show the Food and Drug Administration that safety and efficacy aren’t affected by a switch to biosimilar from an originator biologic. Extrapolation from one indication to another can be made – with scientific justification.

Rheumatologists are mindful of the potential differences between biosimilars and the originator biologic, as evinced in a recent position statement from the American College of Rheumatology. The position statement advises that “extrapolation should be pursued with caution,” and asks for clear labeling when biosimilars have been designated “interchangeable” with their biosimilar. Interchangeability can clear the way for pharmacy substitution of a prescribed biologic, though Dr. Yazdany noted that 40 states have passed legislation requiring prescriber notification.

The FDA is currently using postmarketing pharmacovigilance to monitor biosimilar performance in the real world, and a recent systematic review “should provide some reassurance,” wrote Dr. Yazdany, citing the study, which looked at 14,000 patients who had a total of 14 disease indications for biosimilar use. The 90-article review largely found no differences in safety, efficacy, or immunogenicity between originators and their biosimilars. Dr. Yazdany recommended greater openness to incorporating the European experience in the FDA’s ongoing reassessment.

A further way forward can come through tackling the patent thicket with the proposed bipartisan Biologic Patent Transparency Act, which would require publication of biologic patents in a one-stop publicly searchable database. Going further with legislation to address anticompetitive activity by pharmaceutical companies could shorten the runway to biosimilar launching considerably, she noted.

The complicated landscape of PBMs and rebates affects many sectors of health care, and new policy efforts are needed here as well, she said. Reimbursement strategies – and much-needed continuing medical education – can both ease prescriber unfamiliarity with biosimilars and provide incentives for their use, she concluded.

Dr. Kim concurred that change is needed before the United States is likely to reap significant economic benefit from biosimilars. “The uptake of biosimilars and their impact on overall health care cost needs to be reevaluated when we have more biosimilars available in the next 3-4 years. However, for now, it appears that substantial savings achieved in some European countries – for example, Denmark – may not be possible without systemic reform of the U.S. pharmaceutical market,” she said.

Dr. Yazdany is supported by the Alice Betts Endowed Chair in Arthritis Research, the Russel/Engleman Research Center at the University of California, San Francisco, and the National Institutes of Health. She has received independent research grants from Pfizer and Genentech and research consulting fees from Eli Lilly and AstraZeneca.

Dr. Kim’s study was supported by the division of pharmacoepidemiology and pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Arnold Ventures. Dr. Kim has received research grants to Brigham and Women’s Hospital from Pfizer, AbbVie, Bristol-Myers Squibb, and Roche.

[email protected]

SOURCES: Kim SC et al. Arthritis Rheumatol. 2020 Jan 13. doi: 10.1002/art.41201; Yazdany J. Arthritis Rheumatol. 2020 Jan 10. doi: 10.1002/art.41203.

Although biosimilar versions of tumor necrosis factor inhibitors (TNFis) have been available to U.S. rheumatologists and their patients for over 3 years, uptake has thus far been slow.

monkeybusinessimages/thinkstockphotos.com

In an analysis of data from a large commercial payer, the two available biosimilars for infliximab (Remicade) accounted for less than 1% of TNFi prescribing since the first biosimilar to infliximab was approved in 2016.

The study, published in Arthritis & Rheumatology, involved a total of 1.1 million TNFi prescriptions or infusions received by 95,906 patients from 2016 to 2019. Investigators found that uptake of biosimilar infliximab was essentially flat, standing at 0.1% of prescribing in the second quarter of 2017, and topping out at 0.9% in the first quarter of 2019. For branded infliximab, prescribing was also stable, but accounted for about 20% of overall biologic dispensing in each quarter of the period studied.

There are currently two biosimilar medications to the originator infliximab, which is one of five originator biologics available to treat rheumatic diseases in the United States: infliximab-dyyb (Inflectra) and infliximab-abda (Renflexis). The former was approved in 2016 and the latter in 2017, said study author Seoyoung C. Kim, MD, ScD, of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston, and her coauthors.

“Our paper reports a disappointingly low uptake of biosimilar infliximab since the first quarter of 2017 using claims data from a large private health plan. The main and maybe the only reason to consider using a biosimilar is cost saving,” said Dr. Kim in an interview. “Our results suggest that current modest cost savings from infliximab biosimilars in the U.S. are not sufficient to promote their widespread use.”

In the payer database study conducted by Dr. Kim and colleagues, the insurer paid similar mean amounts per patient per quarter for originator and biosimilar infliximab in mid-2017 ($8,322 versus $8,656). By the end of 2018, a gap appeared, with the insurer paying a mean quarterly per-patient sum of $8,111 for biosimilar infliximab compared with $9,535 for the branded biologic.

“The lack of market penetration and very modest price reductions for biosimilars have left policymakers, payers, physicians, and the public frustrated, particularly because sales in Europe continue to rapidly expand and robust cost-savings have materialized,” wrote Jinoos Yazdany, MD, MPH, in an editorial accompanying the study.

Dr. Yazdany, professor and chief of the division of rheumatology at the University of California, San Francisco, noted that increased spending on biologics in the United States – which increased by 50% from 2014 to 2018 – has been driven by rising prices as well as increased uptake of biologic therapies.

At least in part, Europe has been able to reap cost savings where the United States hasn’t because fundamental differences in health care reimbursement can ease sweeping biosimilar adoption, Dr. Yazdany noted. “Countries like Denmark and Sweden, using the negotiating and purchasing power of their single-payer systems have instituted a winner-takes-all bidding system,” with Denmark seeing cost savings of up to two-thirds when bidding was combined with mandatory switching, she said.

The continued market dominance of originator infliximab means that savings from biosimilars have thus far amounted to about $91 million, far short of the $1 billion that the Congressional Budget Office had projected for this date, Dr. Yazdany said.

One problem in the adoption of biosimilars by U.S. rheumatologists may have been uneven marketing and pricing across different types of practice, Colin C. Edgerton, MD, a rheumatologist at Low Country Rheumatology in South Carolina and chair of the American College of Rheumatology’s Committee on Rheumatologic Care, said in an interview.

“Rheumatologists have generally developed comfort with biosimilars, although this is not universal. The core message, that all biologics vary and that this is OK, is getting out. In general, rheumatologists also understand the problem with high drug prices and the threat to patient access,” Dr. Edgerton said. But “the early marketing and pricing focus for biosimilars seemed to be on hospitals and facilities, and this did not work effectively for community rheumatologists, where the majority of care is delivered. We have been pleased to see a manufacturer pivot toward community rheumatology where additional efforts need to be made to bend the curve on biosimilar adoption. It is critical for practices with experience using biosimilars to educate peers, and this is where networks of practicing rheumatologists are important.”

In Dr. Yazdany’s editorial, she cited four structural factors impeding biosimilar uptake and downstream savings.

First, she cites ongoing actions by pharmaceutical companies, which create a “patent thicket” that has the effect of fencing off originator biologics from biosimilars long beyond the original 12-year exclusivity period. Supporting the notion that “patent thickets” are a common strategy, Dr. Yazdany noted that almost half of the patent applications that AbbVie has filed for adalimumab (Humira) have come in after the original exclusivity period expired in 2014. Humira’s price has risen 18% yearly during this period.

The complicated role played by pharmacy benefit managers (PBMs) is another factor in slow adoption, said Dr. Yazdany: When manufacturers offer rebates to PBMs, the price of the originator biologic may be less than its biosimilar. Further, manufacturers may sign multiyear rebate agreements just before a biosimilar launch; PBMs are also sometimes threatened with the withdrawal of rebates if they offer biosimilars, she noted.

Third, prescriber inertia may also be at play, Dr. Yazdany noted, not least because patients often see little difference in out-of-pocket costs when they make the switch to a biosimilar – PBM rebates are not necessarily passed on to patients. Payers may not reimburse a biosimilar, or formularies can be built without them, influencing prescribing, and there’s usually no reimbursement incentive for biosimilar prescribing in the nonpublic sector, she said. To the contrary, infusing a drug with a higher price often means higher reimbursement for the administering clinician, since commercial insurance reimbursement is often calculated as a percent of the charge for the drug.

Further contributing to inertia is the extra time required for patient education and writing a new set of orders – all work that can’t be captured for extra reimbursement. Dr. Edgerton said that rheumatologists can talk with patients about the “nocebo effect” relating to biosimilars. “This is a phenomenon in which patients are thought to experience worsening symptoms associated with negative beliefs about biosimilars. There has been a study in Arthritis Care & Research addressing this concern. The authors found that positive framing of biosimilars led to more participants being willing to switch than negative framing. This suggests that clinicians have an important role in informing patients about biosimilars, and addressing hesitancy.”

Finally, Dr. Yazdany pointed out that for a pharmaceutical company pursuing biosimilar approval, the regulatory pathway itself can provide its own set of complications and confusion. Biosimilars are not exact molecular replicas of the originator biologic, and these differences can change efficacy and immunogenicity, and also affect stability. Hence, a company wishing to market a biosimilar has to show the Food and Drug Administration that safety and efficacy aren’t affected by a switch to biosimilar from an originator biologic. Extrapolation from one indication to another can be made – with scientific justification.

Rheumatologists are mindful of the potential differences between biosimilars and the originator biologic, as evinced in a recent position statement from the American College of Rheumatology. The position statement advises that “extrapolation should be pursued with caution,” and asks for clear labeling when biosimilars have been designated “interchangeable” with their biosimilar. Interchangeability can clear the way for pharmacy substitution of a prescribed biologic, though Dr. Yazdany noted that 40 states have passed legislation requiring prescriber notification.

The FDA is currently using postmarketing pharmacovigilance to monitor biosimilar performance in the real world, and a recent systematic review “should provide some reassurance,” wrote Dr. Yazdany, citing the study, which looked at 14,000 patients who had a total of 14 disease indications for biosimilar use. The 90-article review largely found no differences in safety, efficacy, or immunogenicity between originators and their biosimilars. Dr. Yazdany recommended greater openness to incorporating the European experience in the FDA’s ongoing reassessment.

A further way forward can come through tackling the patent thicket with the proposed bipartisan Biologic Patent Transparency Act, which would require publication of biologic patents in a one-stop publicly searchable database. Going further with legislation to address anticompetitive activity by pharmaceutical companies could shorten the runway to biosimilar launching considerably, she noted.

The complicated landscape of PBMs and rebates affects many sectors of health care, and new policy efforts are needed here as well, she said. Reimbursement strategies – and much-needed continuing medical education – can both ease prescriber unfamiliarity with biosimilars and provide incentives for their use, she concluded.

Dr. Kim concurred that change is needed before the United States is likely to reap significant economic benefit from biosimilars. “The uptake of biosimilars and their impact on overall health care cost needs to be reevaluated when we have more biosimilars available in the next 3-4 years. However, for now, it appears that substantial savings achieved in some European countries – for example, Denmark – may not be possible without systemic reform of the U.S. pharmaceutical market,” she said.

Dr. Yazdany is supported by the Alice Betts Endowed Chair in Arthritis Research, the Russel/Engleman Research Center at the University of California, San Francisco, and the National Institutes of Health. She has received independent research grants from Pfizer and Genentech and research consulting fees from Eli Lilly and AstraZeneca.

Dr. Kim’s study was supported by the division of pharmacoepidemiology and pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Arnold Ventures. Dr. Kim has received research grants to Brigham and Women’s Hospital from Pfizer, AbbVie, Bristol-Myers Squibb, and Roche.

[email protected]

SOURCES: Kim SC et al. Arthritis Rheumatol. 2020 Jan 13. doi: 10.1002/art.41201; Yazdany J. Arthritis Rheumatol. 2020 Jan 10. doi: 10.1002/art.41203.

Tumor necrosis factor inhibitors may slow radiographic progression in the spine of patients with ankylosing spondylitis after at least 4 years of use, according to an analysis of studies with low risk of bias, but no evidence exists for slowed disease progression at the sacroiliac joint, according to a systematic review and meta-analysis of 24 studies.

The review, conducted by Paras Karmacharya, MBBS, and colleagues at the Mayo Clinic in Rochester, Minn., did not find a significant protective effect overall for tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression of ankylosing spondylitis at the spine at 2 and 4 years. But when the researchers restricted the analysis to six studies of TNFi with low risk of bias, the results were significant for slowing radiographic progression at 4 years or more (modified Stoke Ankylosing Spondylitis Spine Score [mSASSS] difference, –2.17).

NSAIDs did not show any benefit in slowing progression at either the spine or sacroiliac joint over a shorter 2-year time span for which results were available. The single study of secukinumab (Cosentyx) that was included in the analysis did not show a significant difference in radiographic progression over 2 years (mean mSASSS difference, –0.34).

For the few studies that included data on radiographic progression in patients with nonradiographic axial spondyloarthritis, there was no effect seen on the spine with either high or low NSAID use at 2 years and no evidence for an effect of TNFi on progression at the sacroiliac joint.

“Although our study showed a significant effect of TNFi on long-term radiographic progression (in sensitivity analysis), none of the included studies provide prospective, long-term, controlled comparison. Most included studies were judged to have a low risk of bias; however predominance of observational and open-label extensions of randomized, controlled trials limits overall level of evidence,” the authors wrote in Arthritis & Rheumatology.

Any benefits of early treatment on slowing the natural progression of disease might support introducing the treatment early with a treat-to-target strategy, similar to RA, the researchers noted. However, “the current guidelines recommend against this due to lack of evidence.”

The analysis involved 18 studies with TNFi, 8 with NSAIDs, and 1 with secukinumab (3 studies contained data for both NSAIDs and TNFi). The investigators used a change of 2 mSASSS units in 2 years or one new syndesmophyte formation in 2 years as the primary endpoint for radiographic progression.

“Further studies should explore the effect of NSAIDs and biologics alone and in combination in patients with early axial spondyloarthritis; their use in the group with high risk of progression should be evaluated with a follow-up [longer than] 4 years to see if effects are more pronounced over time. Newer measures with higher sensitivity to detect structural changes, such as those based on quantitative low-dose CT should be compared to mSASSS for use in clinical trials,” the researchers concluded.

The work was funded by various grants from the National Institutes of Health. The authors reported no relevant disclosures.

[email protected]

SOURCE: Karmacharya P et al. Arthritis Rheumatol. 2020 Jan 20. doi: 10.1002/art.41206.

Tumor necrosis factor inhibitors may slow radiographic progression in the spine of patients with ankylosing spondylitis after at least 4 years of use, according to an analysis of studies with low risk of bias, but no evidence exists for slowed disease progression at the sacroiliac joint, according to a systematic review and meta-analysis of 24 studies.

The review, conducted by Paras Karmacharya, MBBS, and colleagues at the Mayo Clinic in Rochester, Minn., did not find a significant protective effect overall for tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression of ankylosing spondylitis at the spine at 2 and 4 years. But when the researchers restricted the analysis to six studies of TNFi with low risk of bias, the results were significant for slowing radiographic progression at 4 years or more (modified Stoke Ankylosing Spondylitis Spine Score [mSASSS] difference, –2.17).

NSAIDs did not show any benefit in slowing progression at either the spine or sacroiliac joint over a shorter 2-year time span for which results were available. The single study of secukinumab (Cosentyx) that was included in the analysis did not show a significant difference in radiographic progression over 2 years (mean mSASSS difference, –0.34).

For the few studies that included data on radiographic progression in patients with nonradiographic axial spondyloarthritis, there was no effect seen on the spine with either high or low NSAID use at 2 years and no evidence for an effect of TNFi on progression at the sacroiliac joint.

“Although our study showed a significant effect of TNFi on long-term radiographic progression (in sensitivity analysis), none of the included studies provide prospective, long-term, controlled comparison. Most included studies were judged to have a low risk of bias; however predominance of observational and open-label extensions of randomized, controlled trials limits overall level of evidence,” the authors wrote in Arthritis & Rheumatology.

Any benefits of early treatment on slowing the natural progression of disease might support introducing the treatment early with a treat-to-target strategy, similar to RA, the researchers noted. However, “the current guidelines recommend against this due to lack of evidence.”

The analysis involved 18 studies with TNFi, 8 with NSAIDs, and 1 with secukinumab (3 studies contained data for both NSAIDs and TNFi). The investigators used a change of 2 mSASSS units in 2 years or one new syndesmophyte formation in 2 years as the primary endpoint for radiographic progression.

“Further studies should explore the effect of NSAIDs and biologics alone and in combination in patients with early axial spondyloarthritis; their use in the group with high risk of progression should be evaluated with a follow-up [longer than] 4 years to see if effects are more pronounced over time. Newer measures with higher sensitivity to detect structural changes, such as those based on quantitative low-dose CT should be compared to mSASSS for use in clinical trials,” the researchers concluded.

The work was funded by various grants from the National Institutes of Health. The authors reported no relevant disclosures.

[email protected]

SOURCE: Karmacharya P et al. Arthritis Rheumatol. 2020 Jan 20. doi: 10.1002/art.41206.

Tumor necrosis factor inhibitors may slow radiographic progression in the spine of patients with ankylosing spondylitis after at least 4 years of use, according to an analysis of studies with low risk of bias, but no evidence exists for slowed disease progression at the sacroiliac joint, according to a systematic review and meta-analysis of 24 studies.

The review, conducted by Paras Karmacharya, MBBS, and colleagues at the Mayo Clinic in Rochester, Minn., did not find a significant protective effect overall for tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression of ankylosing spondylitis at the spine at 2 and 4 years. But when the researchers restricted the analysis to six studies of TNFi with low risk of bias, the results were significant for slowing radiographic progression at 4 years or more (modified Stoke Ankylosing Spondylitis Spine Score [mSASSS] difference, –2.17).

NSAIDs did not show any benefit in slowing progression at either the spine or sacroiliac joint over a shorter 2-year time span for which results were available. The single study of secukinumab (Cosentyx) that was included in the analysis did not show a significant difference in radiographic progression over 2 years (mean mSASSS difference, –0.34).

For the few studies that included data on radiographic progression in patients with nonradiographic axial spondyloarthritis, there was no effect seen on the spine with either high or low NSAID use at 2 years and no evidence for an effect of TNFi on progression at the sacroiliac joint.

“Although our study showed a significant effect of TNFi on long-term radiographic progression (in sensitivity analysis), none of the included studies provide prospective, long-term, controlled comparison. Most included studies were judged to have a low risk of bias; however predominance of observational and open-label extensions of randomized, controlled trials limits overall level of evidence,” the authors wrote in Arthritis & Rheumatology.

Any benefits of early treatment on slowing the natural progression of disease might support introducing the treatment early with a treat-to-target strategy, similar to RA, the researchers noted. However, “the current guidelines recommend against this due to lack of evidence.”

The analysis involved 18 studies with TNFi, 8 with NSAIDs, and 1 with secukinumab (3 studies contained data for both NSAIDs and TNFi). The investigators used a change of 2 mSASSS units in 2 years or one new syndesmophyte formation in 2 years as the primary endpoint for radiographic progression.

“Further studies should explore the effect of NSAIDs and biologics alone and in combination in patients with early axial spondyloarthritis; their use in the group with high risk of progression should be evaluated with a follow-up [longer than] 4 years to see if effects are more pronounced over time. Newer measures with higher sensitivity to detect structural changes, such as those based on quantitative low-dose CT should be compared to mSASSS for use in clinical trials,” the researchers concluded.

The work was funded by various grants from the National Institutes of Health. The authors reported no relevant disclosures.

[email protected]

SOURCE: Karmacharya P et al. Arthritis Rheumatol. 2020 Jan 20. doi: 10.1002/art.41206.

ATLANTA – Patients taking biologics who received latent tuberculosis testing on an annual basis were unlikely to convert from a negative QuantiFERON test to a positive result, which suggests that the test may be unnecessary for patients without new tuberculosis risk factors, according to research presented at the annual meeting of the American College of Rheumatology.

In addition, nearly all of the cost of repeat testing for latent tuberculosis infection (LTBI) went to patients who were not diagnosed with or treated for LTBI, noted Urmi Khanna, MD, a dermatologist with the Cleveland Clinic.

“All in all, about $1.4 million U.S. dollars was spent just on additional QuantiFERON testing, and only 1% of this additional cost was actually spent on testing patients who were diagnosed with and treated for latent tuberculosis,” Dr. Khanna said in her presentation at the meeting.

“Based on this study, we would like to propose that, in low incidence TB regions such as the United States, repeat LTBI testing in patients on biologic therapies should be focused on patients who have new risk factors for TB infection since their last screening,” she said.

The National Psoriasis Foundation has recommended patients be screened annually for LTBI, and the Centers for Disease Control and Prevention and the ACR have recommended patients taking biologics be screened annually for LTBI if they have new risk factors for TB, such as coming into contact with immigrants, a person infected with TB, immunosuppressed individuals, or persons working in areas where TB might be present. Annual screening was also recently added to the Medicare Merit-Based Incentive Payment System (MIPS), which will affect physician reimbursement. “Based on [the addition of this quality outcome measure], we expect that more and more physicians will adopt this practice of annual LTBI screening in all patients on biologics,” Dr. Khanna said.

She and her colleagues examined QuantiFERON tuberculosis test (QFT) results of 10,914 patients from the Cleveland Clinic Foundation between August 2007 and March 2019 where patients were receiving systemic biologic therapy for inflammatory or autoimmune conditions, including nearly 32% with inflammatory bowel disease, 29% with rheumatoid arthritis, and 25% with psoriatic disease. Overall, 5,212 patients were included in the final analysis, and patients had a median of three QFT results. Patients had a median age of 41 years, had taken an average of 1.80 biologics during follow-up, and had a median biologic therapy duration of about 49 months. The most common biologics used were adalimumab (33%), etanercept (17%), and infliximab (17%).

Of these patients, 4,561 patients had negative QFTs (88%), 172 patients had one or more positive QFTs (3%), and 479 patients had one or more indeterminate QFTs (9%). For patients who converted from a negative QFT to a positive QFT, the most common risk factors were exposure to someone with TB (26%), immigrating or traveling to an endemic area (26%), and occupational exposure (16%).

Within the group with one or more positive QFTs, there were 108 patients with baseline positive QFTs prior to starting biologic therapy (2.1%), 61 patients who converted from a baseline negative QFT to a positive QFT (1.2%), and 3 patients where a positive result overlapped with a negative result (0.1%). The majority of patients who converted to a positive QFT result had borderline positive results (70.5%), defined as 0.35 to 1 IU/mL, compared with 29.5% of converters who had a positive QFT result of more than 1.0 IU/mL.

Among the 61 patients who converted to a positive QFT result, 28 patients with LTBI (46%) and 1 patient with an active case of TB (2%) were diagnosed and treated. The active TB case was a 29-year-old patient with inflammatory bowel disease and ankylosing spondylitis receiving adalimumab who had recently traveled to India.

The researchers also examined the cost of additional QFTs in each group. Among negative QFTs, the cost of an additional 9,611 tests was $1,201,375. The cost of additional tests for indeterminate QFTs was $136,200, but Dr. Khanna noted that 99.99% of additional tests in this group were for patients never diagnosed with or treated for LTBI. Additional tests for positive QFTs cost another $47,700, and 26.1% of patients in this group were diagnosed and received treatment for LTBI, compared with 73.9% who did not receive an LTBI diagnosis or treatment.

In the discussion session following the presentation, Dr. Khanna emphasized that discontinuing annual screening in low-risk patients was not standard of care at the Cleveland Clinic, and this study was conducted to raise awareness of focusing testing on patients with new TB risk factors.

Dr. Khanna reported no relevant financial disclosures. A few of her coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Khanna U et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1802.

ATLANTA – Patients taking biologics who received latent tuberculosis testing on an annual basis were unlikely to convert from a negative QuantiFERON test to a positive result, which suggests that the test may be unnecessary for patients without new tuberculosis risk factors, according to research presented at the annual meeting of the American College of Rheumatology.

In addition, nearly all of the cost of repeat testing for latent tuberculosis infection (LTBI) went to patients who were not diagnosed with or treated for LTBI, noted Urmi Khanna, MD, a dermatologist with the Cleveland Clinic.

“All in all, about $1.4 million U.S. dollars was spent just on additional QuantiFERON testing, and only 1% of this additional cost was actually spent on testing patients who were diagnosed with and treated for latent tuberculosis,” Dr. Khanna said in her presentation at the meeting.

“Based on this study, we would like to propose that, in low incidence TB regions such as the United States, repeat LTBI testing in patients on biologic therapies should be focused on patients who have new risk factors for TB infection since their last screening,” she said.

The National Psoriasis Foundation has recommended patients be screened annually for LTBI, and the Centers for Disease Control and Prevention and the ACR have recommended patients taking biologics be screened annually for LTBI if they have new risk factors for TB, such as coming into contact with immigrants, a person infected with TB, immunosuppressed individuals, or persons working in areas where TB might be present. Annual screening was also recently added to the Medicare Merit-Based Incentive Payment System (MIPS), which will affect physician reimbursement. “Based on [the addition of this quality outcome measure], we expect that more and more physicians will adopt this practice of annual LTBI screening in all patients on biologics,” Dr. Khanna said.

She and her colleagues examined QuantiFERON tuberculosis test (QFT) results of 10,914 patients from the Cleveland Clinic Foundation between August 2007 and March 2019 where patients were receiving systemic biologic therapy for inflammatory or autoimmune conditions, including nearly 32% with inflammatory bowel disease, 29% with rheumatoid arthritis, and 25% with psoriatic disease. Overall, 5,212 patients were included in the final analysis, and patients had a median of three QFT results. Patients had a median age of 41 years, had taken an average of 1.80 biologics during follow-up, and had a median biologic therapy duration of about 49 months. The most common biologics used were adalimumab (33%), etanercept (17%), and infliximab (17%).

Of these patients, 4,561 patients had negative QFTs (88%), 172 patients had one or more positive QFTs (3%), and 479 patients had one or more indeterminate QFTs (9%). For patients who converted from a negative QFT to a positive QFT, the most common risk factors were exposure to someone with TB (26%), immigrating or traveling to an endemic area (26%), and occupational exposure (16%).

Within the group with one or more positive QFTs, there were 108 patients with baseline positive QFTs prior to starting biologic therapy (2.1%), 61 patients who converted from a baseline negative QFT to a positive QFT (1.2%), and 3 patients where a positive result overlapped with a negative result (0.1%). The majority of patients who converted to a positive QFT result had borderline positive results (70.5%), defined as 0.35 to 1 IU/mL, compared with 29.5% of converters who had a positive QFT result of more than 1.0 IU/mL.

Among the 61 patients who converted to a positive QFT result, 28 patients with LTBI (46%) and 1 patient with an active case of TB (2%) were diagnosed and treated. The active TB case was a 29-year-old patient with inflammatory bowel disease and ankylosing spondylitis receiving adalimumab who had recently traveled to India.

The researchers also examined the cost of additional QFTs in each group. Among negative QFTs, the cost of an additional 9,611 tests was $1,201,375. The cost of additional tests for indeterminate QFTs was $136,200, but Dr. Khanna noted that 99.99% of additional tests in this group were for patients never diagnosed with or treated for LTBI. Additional tests for positive QFTs cost another $47,700, and 26.1% of patients in this group were diagnosed and received treatment for LTBI, compared with 73.9% who did not receive an LTBI diagnosis or treatment.

In the discussion session following the presentation, Dr. Khanna emphasized that discontinuing annual screening in low-risk patients was not standard of care at the Cleveland Clinic, and this study was conducted to raise awareness of focusing testing on patients with new TB risk factors.

Dr. Khanna reported no relevant financial disclosures. A few of her coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Khanna U et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1802.

ATLANTA – Patients taking biologics who received latent tuberculosis testing on an annual basis were unlikely to convert from a negative QuantiFERON test to a positive result, which suggests that the test may be unnecessary for patients without new tuberculosis risk factors, according to research presented at the annual meeting of the American College of Rheumatology.

In addition, nearly all of the cost of repeat testing for latent tuberculosis infection (LTBI) went to patients who were not diagnosed with or treated for LTBI, noted Urmi Khanna, MD, a dermatologist with the Cleveland Clinic.

“All in all, about $1.4 million U.S. dollars was spent just on additional QuantiFERON testing, and only 1% of this additional cost was actually spent on testing patients who were diagnosed with and treated for latent tuberculosis,” Dr. Khanna said in her presentation at the meeting.

“Based on this study, we would like to propose that, in low incidence TB regions such as the United States, repeat LTBI testing in patients on biologic therapies should be focused on patients who have new risk factors for TB infection since their last screening,” she said.

The National Psoriasis Foundation has recommended patients be screened annually for LTBI, and the Centers for Disease Control and Prevention and the ACR have recommended patients taking biologics be screened annually for LTBI if they have new risk factors for TB, such as coming into contact with immigrants, a person infected with TB, immunosuppressed individuals, or persons working in areas where TB might be present. Annual screening was also recently added to the Medicare Merit-Based Incentive Payment System (MIPS), which will affect physician reimbursement. “Based on [the addition of this quality outcome measure], we expect that more and more physicians will adopt this practice of annual LTBI screening in all patients on biologics,” Dr. Khanna said.

She and her colleagues examined QuantiFERON tuberculosis test (QFT) results of 10,914 patients from the Cleveland Clinic Foundation between August 2007 and March 2019 where patients were receiving systemic biologic therapy for inflammatory or autoimmune conditions, including nearly 32% with inflammatory bowel disease, 29% with rheumatoid arthritis, and 25% with psoriatic disease. Overall, 5,212 patients were included in the final analysis, and patients had a median of three QFT results. Patients had a median age of 41 years, had taken an average of 1.80 biologics during follow-up, and had a median biologic therapy duration of about 49 months. The most common biologics used were adalimumab (33%), etanercept (17%), and infliximab (17%).

Of these patients, 4,561 patients had negative QFTs (88%), 172 patients had one or more positive QFTs (3%), and 479 patients had one or more indeterminate QFTs (9%). For patients who converted from a negative QFT to a positive QFT, the most common risk factors were exposure to someone with TB (26%), immigrating or traveling to an endemic area (26%), and occupational exposure (16%).

Within the group with one or more positive QFTs, there were 108 patients with baseline positive QFTs prior to starting biologic therapy (2.1%), 61 patients who converted from a baseline negative QFT to a positive QFT (1.2%), and 3 patients where a positive result overlapped with a negative result (0.1%). The majority of patients who converted to a positive QFT result had borderline positive results (70.5%), defined as 0.35 to 1 IU/mL, compared with 29.5% of converters who had a positive QFT result of more than 1.0 IU/mL.

Among the 61 patients who converted to a positive QFT result, 28 patients with LTBI (46%) and 1 patient with an active case of TB (2%) were diagnosed and treated. The active TB case was a 29-year-old patient with inflammatory bowel disease and ankylosing spondylitis receiving adalimumab who had recently traveled to India.

The researchers also examined the cost of additional QFTs in each group. Among negative QFTs, the cost of an additional 9,611 tests was $1,201,375. The cost of additional tests for indeterminate QFTs was $136,200, but Dr. Khanna noted that 99.99% of additional tests in this group were for patients never diagnosed with or treated for LTBI. Additional tests for positive QFTs cost another $47,700, and 26.1% of patients in this group were diagnosed and received treatment for LTBI, compared with 73.9% who did not receive an LTBI diagnosis or treatment.

In the discussion session following the presentation, Dr. Khanna emphasized that discontinuing annual screening in low-risk patients was not standard of care at the Cleveland Clinic, and this study was conducted to raise awareness of focusing testing on patients with new TB risk factors.

Dr. Khanna reported no relevant financial disclosures. A few of her coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Khanna U et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1802.

The Food and Drug Administration has approved the biosimilar infliximab-axxq (Avsola) for various indications, making it the fourth biosimilar of infliximab (Remicade) to be cleared for marketing by the agency.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The tumor necrosis factor inhibitor is indicated for patients with Crohn’s disease or ulcerative colitis who are aged 6 years and older, RA in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. The approval is based on numerous trials. The most common adverse reactions are infections, infusion-related reactions, headache, and abdominal pain.

Full prescribing information can be found on the FDA website, as can more information about biosimilars.

[email protected]

The Food and Drug Administration has approved the biosimilar infliximab-axxq (Avsola) for various indications, making it the fourth biosimilar of infliximab (Remicade) to be cleared for marketing by the agency.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The tumor necrosis factor inhibitor is indicated for patients with Crohn’s disease or ulcerative colitis who are aged 6 years and older, RA in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. The approval is based on numerous trials. The most common adverse reactions are infections, infusion-related reactions, headache, and abdominal pain.

Full prescribing information can be found on the FDA website, as can more information about biosimilars.

[email protected]

The Food and Drug Administration has approved the biosimilar infliximab-axxq (Avsola) for various indications, making it the fourth biosimilar of infliximab (Remicade) to be cleared for marketing by the agency.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The tumor necrosis factor inhibitor is indicated for patients with Crohn’s disease or ulcerative colitis who are aged 6 years and older, RA in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. The approval is based on numerous trials. The most common adverse reactions are infections, infusion-related reactions, headache, and abdominal pain.

Full prescribing information can be found on the FDA website, as can more information about biosimilars.

[email protected]

The findings from the C-axSpAnd study that Jonathan Kay, MD, and colleagues reported at the annual meeting of the American College of Rheumatology are not surprising. Earlier studies in patients with ankylosing spondylitis showed that short symptom duration is one of the best predictors of good treatment response to TNFi therapy. The highest response rates were obtained in studies conducted in axSpA patients with symptom duration of less than 5 years or even less than 3 years. Since nonradiographic axial spondyloarthritis (nr-axSpA) and r-axSpA are considered as two stages of one disease, it is logical that the same effect is also observed in studies in nr-axSpA. Indeed, in the first study of a tumor necrosis factor inhibitor (TNFi) in nr-axSpA (ABILITY-1), patients with symptom duration less than 5 years responded much better to the TNFi adalimumab than did those with longer symptom duration, and the delta of the response between adalimumab and placebo was much greater. All these results together indicate that early disease stage associated with favorable treatment response in axSpA is better defined by symptom duration than by the presence or absence of structural damage in the sacroiliac joints. Furthermore, these data stress the importance of the early diagnosis in axSpA.

We also know from observational studies and subanalyses from clinical trials that treatment with monoclonal antibodies against TNF is associated with reduction of uveitis flares in axSpA. However, no prospective clinical studies had been conducted with acute anterior uveitis flares as the primary outcome until the C-VIEW study, which was presented by Irene E. van der Horst-Bruinsma, MD, PhD, at ACR 2019. The results of C-VIEW are therefore the first to prospectively address the question of reduction of uveitis flares under TNFi. The main limitation of the study is the lack of a control group, which makes interpretation of the results difficult because it is not clear to what extent the natural course of the disease – which might involve very long flare-free periods lasting from months to years – contributed to the reduction of flares. A randomized, controlled study aimed at label extension is highly desired for patients with acute anterior uveitis, especially for those with a frequently relapsing course resistant to local treatment.

Denis Poddubnyy, MD , is head of the rheumatology department at Charite-Universitätsmedizin Berlin. He disclosed receiving research grants from AbbVie, Lilly, Merck, Novartis, and Pfizer, as well as receiving consultancy or speaker fees from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and UCB.

The findings from the C-axSpAnd study that Jonathan Kay, MD, and colleagues reported at the annual meeting of the American College of Rheumatology are not surprising. Earlier studies in patients with ankylosing spondylitis showed that short symptom duration is one of the best predictors of good treatment response to TNFi therapy. The highest response rates were obtained in studies conducted in axSpA patients with symptom duration of less than 5 years or even less than 3 years. Since nonradiographic axial spondyloarthritis (nr-axSpA) and r-axSpA are considered as two stages of one disease, it is logical that the same effect is also observed in studies in nr-axSpA. Indeed, in the first study of a tumor necrosis factor inhibitor (TNFi) in nr-axSpA (ABILITY-1), patients with symptom duration less than 5 years responded much better to the TNFi adalimumab than did those with longer symptom duration, and the delta of the response between adalimumab and placebo was much greater. All these results together indicate that early disease stage associated with favorable treatment response in axSpA is better defined by symptom duration than by the presence or absence of structural damage in the sacroiliac joints. Furthermore, these data stress the importance of the early diagnosis in axSpA.

We also know from observational studies and subanalyses from clinical trials that treatment with monoclonal antibodies against TNF is associated with reduction of uveitis flares in axSpA. However, no prospective clinical studies had been conducted with acute anterior uveitis flares as the primary outcome until the C-VIEW study, which was presented by Irene E. van der Horst-Bruinsma, MD, PhD, at ACR 2019. The results of C-VIEW are therefore the first to prospectively address the question of reduction of uveitis flares under TNFi. The main limitation of the study is the lack of a control group, which makes interpretation of the results difficult because it is not clear to what extent the natural course of the disease – which might involve very long flare-free periods lasting from months to years – contributed to the reduction of flares. A randomized, controlled study aimed at label extension is highly desired for patients with acute anterior uveitis, especially for those with a frequently relapsing course resistant to local treatment.

Denis Poddubnyy, MD , is head of the rheumatology department at Charite-Universitätsmedizin Berlin. He disclosed receiving research grants from AbbVie, Lilly, Merck, Novartis, and Pfizer, as well as receiving consultancy or speaker fees from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and UCB.

The findings from the C-axSpAnd study that Jonathan Kay, MD, and colleagues reported at the annual meeting of the American College of Rheumatology are not surprising. Earlier studies in patients with ankylosing spondylitis showed that short symptom duration is one of the best predictors of good treatment response to TNFi therapy. The highest response rates were obtained in studies conducted in axSpA patients with symptom duration of less than 5 years or even less than 3 years. Since nonradiographic axial spondyloarthritis (nr-axSpA) and r-axSpA are considered as two stages of one disease, it is logical that the same effect is also observed in studies in nr-axSpA. Indeed, in the first study of a tumor necrosis factor inhibitor (TNFi) in nr-axSpA (ABILITY-1), patients with symptom duration less than 5 years responded much better to the TNFi adalimumab than did those with longer symptom duration, and the delta of the response between adalimumab and placebo was much greater. All these results together indicate that early disease stage associated with favorable treatment response in axSpA is better defined by symptom duration than by the presence or absence of structural damage in the sacroiliac joints. Furthermore, these data stress the importance of the early diagnosis in axSpA.

We also know from observational studies and subanalyses from clinical trials that treatment with monoclonal antibodies against TNF is associated with reduction of uveitis flares in axSpA. However, no prospective clinical studies had been conducted with acute anterior uveitis flares as the primary outcome until the C-VIEW study, which was presented by Irene E. van der Horst-Bruinsma, MD, PhD, at ACR 2019. The results of C-VIEW are therefore the first to prospectively address the question of reduction of uveitis flares under TNFi. The main limitation of the study is the lack of a control group, which makes interpretation of the results difficult because it is not clear to what extent the natural course of the disease – which might involve very long flare-free periods lasting from months to years – contributed to the reduction of flares. A randomized, controlled study aimed at label extension is highly desired for patients with acute anterior uveitis, especially for those with a frequently relapsing course resistant to local treatment.

Denis Poddubnyy, MD , is head of the rheumatology department at Charite-Universitätsmedizin Berlin. He disclosed receiving research grants from AbbVie, Lilly, Merck, Novartis, and Pfizer, as well as receiving consultancy or speaker fees from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and UCB.

ATLANTA – Certolizumab pegol, a PEGylated, monoclonal, anti–tumor necrosis factor antibody, reduces recurrent acute anterior uveitis flares and improves disease activity in patients with axial spondyloarthritis, according to findings from the open-label, 96-week, phase 4 C-VIEW study.

Sharon Worcester/MDedge News

When given earlier in the course of disease, the treatment, which is the only Food and Drug Administration–approved tumor necrosis factor inhibitor (TNFi) for the treatment of nonradiographic axial spondyloarthritis (nr-axSpA), also shortens symptom duration, a post hoc analysis of data from the multicenter, phase 3 C-axSpAnd study suggests. The findings from both studies were presented during a session at the annual meeting of the American College of Rheumatology.
 

C-VIEW

In 85 patients with active axSpA who completed 48 weeks of certolizumab pegol therapy in the C-VIEW study, the acute anterior uveitis (AAU) flare incidence over 48 weeks was a mean of 0.2, compared with 1.5 flares per person in the 48 weeks prior to treatment initiation, reported Irene E. van der Horst-Bruinsma, MD, PhD, of Amsterdam University Medical Center. The comparison was adjusted for possible within-patient correlations, flare period (pre- and post baseline), and axSpA disease duration.

This finding, from a preplanned interim analysis, represented a flare incidence of 18.7 versus 146.6 per 100 patient-years, during treatment versus prior to treatment – an 87% reduction – and the difference was statistically significant (P less than .001), Dr. van der Horst-Bruinsma said.

The percentage of patients experiencing one flare was 12.4% during therapy, compared with 64% prior to therapy, and the percentage experiencing two or more flares was 2.2% versus 24.7%, respectively, she said, adding that, in the 13 patients who experienced flares both before and during treatment, the mean flare duration was reduced during treatment (58.4 vs. 97.4 days). A comparison of radiographic and nr-axSpA patients showed similar reductions in flares during versus prior to treatment, going from 144.5 to 19.0 flares per 100 patient-years with radiographic disease and from 158.9 to 17.2 flares per 100 patient-years in nr-axSpA.

Furthermore, after 48 weeks of treatment, disease activity had improved substantially, with mean Ankylosing Spondylitis Disease Activity Score (ASDAS) improving from 3.5 to 2.0 at week 48, 94.2% of patients reaching ASDAS clinical improvement at week 48, and mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score decreasing significantly from 6.5 to 3.3 at week 48.

“ASDAS 20 was reached by 75% of the patients, the ASDAS 40 by 54%, and the ASDAS partial remission criteria were reached by 31% of the patients,” she said.

Study participants were adults with a mean age of 46.5 years and active disease according to Assessment of Spondyloarthritis International Society (ASAS) criteria and a history of recurrent AAU flares (either two or more in total, or one or more in the year prior to study entry). They were HLA-B27 positive, eligible for anti-TNF therapy because they had an inadequate response (or contraindication) to at least two prior NSAIDs, were biologic naive, or had failed to respond to no more than one prior anti-TNF agent. Both radiographic and nr-axSpA patients were included, and of 115 who enrolled, 89 initiated treatment, including 76 with radiographic disease and 13 with nonradiographic disease; 85 completed week 48 of treatment.

Certolizumab pegol was given at a loading dose of 400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks through week 96, and was well tolerated. No new safety signals were identified, Dr. van der Horst-Bruinsma said.

“We know that acute anterior uveitis, an inflammation of ... the uveal tract, is the most common extra-articular manifestation in axial spondyloarthritis,” she said. “It is reported in up to 40% of patients and is associated with significant clinical burden.”

AAU is also strongly associated with the HLA-B27 antigen, therefore patients who do not have ankylosing spondylitis but who are HLA-B27 positive also are at risk, she said, noting that previous studies have shown that TNF inhibitors reduce the incidence of AAU flares in patients with radiographic axSpA (ankylosing spondylitis), but that data in nr-axSpA are scarce.

The aim of C-VIEW was to analyze the impact of certolizumab pegol treatment on AAU flares in patients with active radiographic or nr-axSpA and a recent history of AAU, she said.

“C-VIEW was the first study to examine the impact of certolizumab on the incidence of acute anterior uveitis flares in HLA-B27-positive patients with a recent history of acute anterior uveitis, including patients with nr-axSpA ... and in conclusion we can say that these results indicate that certolizumab is a suitable treatment option for patients with axSpA and a history of recurrent acute anterior uveitis,” she said.

C-axSpAnd

In the pivotal 3-year C-axSpAnd study, which included a 52‑week, double-blind, placebo-controlled period, 159 patients with active nr-axSpA, objective signs of inflammation, and previous failure of at least two NSAIDS were treated with certolizumab pegol, and 158 similar patients received placebo. Both groups received nonbiologic background medication.

The results of the trial, published in Arthritis & Rheumatology in March 2019, showed that adding certolizumab pegol to background medication is superior to adding placebo in patients with active nr-axSpA and led to its FDA approval for axSpA in March 2019, but the effects of symptom duration on outcomes with certolizumab pegol have not been well studied, Jonathan Kay, MD, said at the ACR meeting.

The current post hoc analysis stratified patients based on symptom duration and showed that certolizumab pegol recipients with less than 5 years of symptoms at baseline had improved outcomes at weeks 12 and 52, compared with those who had 5 or more years of symptoms at baseline, said Dr. Kay of UMass Memorial Medical Center and the University of Massachusetts, Worcester.

For example, major improvement in ASDAS at week 52, the primary outcome measure, was achieved by 55% of 80 patients with shorter symptom duration, compared with 39.2% of 79 patients with longer symptom duration, and the ASAS 40 responder rates in the groups, respectively, were 58.5% and 36.7% at 12 weeks and 65% and 48.1% at 52 weeks, he said.

Certolizumab pegol recipients with shorter symptom duration also had greater improvement in BASDAI score, nocturnal spinal pain, fatigue, morning stiffness, and the 36-item Short Form Survey physical component score, he noted.

Using a cutoff of 3 years rather than 5 years, responder rates for major improvement in ASDAS and ASAS 40 were still greater in certolizumab pegol–treated patients with shorter symptom duration: At 52 weeks, 56.4% of 55 patients with less than 3 years of symptoms, compared with 42.3% of 104 with 3 or more years of symptoms, achieved major improvement in ASDAS, and ASAS 40 responder rates were 65.5%, compared with 51.9%, respectively.

Response rates in the placebo arm were low, compared with both certolizumab pegol groups, and no consistent trend in outcomes was observed based on symptom duration in that arm, Dr. Kay noted.

Study subjects were adults with a diagnosis of axSpA, active disease, fulfillment of ASAS classification criteria, and at least 12 months of inflammatory back pain. The trial excluded those with radiographic sacroiliitis meeting the modified New York classification criteria and who had exposure to more than one TNFi prior to baseline or primary failure of any TNFi. As in the C-VIEW study, participants were randomized to receive 400 mg certolizumab pegol at weeks 0, 2, and 4, and then 200 mg every 2 weeks thereafter through week 52.

The findings are notable because patients with axSpA – including radiographic disease and nr-axSpA – often experience delays in diagnosis, which can lead to a delay in treatment and a reduced quality of life because of the back pain, fatigue, and morning stiffness that commonly occur with the disease.

“Women, especially, with axial spondyloarthritis experience a longer delay in diagnosis than do male patients,” Dr. Kay noted.

The findings of this post hoc analysis underscore the risks associated with such a delay. “These results imply that early diagnosis enabling earlier treatment is important for patients with nonradiographic axSpA, as it is for patients with radiographic axSpA,” he concluded.

The C-VIEW and C-axSpAnd studies were funded by UCB. Dr. van der Horst-Bruinsma reported receiving honoraria, consulting fees, and/or research grants from UCB as well as from AbbVie, Bristol-Myers Squibb, Merck, Novartis, and Pfizer. Dr. Kay reported receiving grant/research support from Gilead, Pfizer, and UCB, and consulting fees from AbbVie, Alvotech, Boehringer Ingelheim, Celltrion, Merck, Novartis, Samsung Bioepis, Sandoz, and UCB.

[email protected]

SOURCES: van der Horst-Bruinsma I et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 935; Kay J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 936.

ATLANTA – Certolizumab pegol, a PEGylated, monoclonal, anti–tumor necrosis factor antibody, reduces recurrent acute anterior uveitis flares and improves disease activity in patients with axial spondyloarthritis, according to findings from the open-label, 96-week, phase 4 C-VIEW study.

Sharon Worcester/MDedge News

When given earlier in the course of disease, the treatment, which is the only Food and Drug Administration–approved tumor necrosis factor inhibitor (TNFi) for the treatment of nonradiographic axial spondyloarthritis (nr-axSpA), also shortens symptom duration, a post hoc analysis of data from the multicenter, phase 3 C-axSpAnd study suggests. The findings from both studies were presented during a session at the annual meeting of the American College of Rheumatology.
 

C-VIEW

In 85 patients with active axSpA who completed 48 weeks of certolizumab pegol therapy in the C-VIEW study, the acute anterior uveitis (AAU) flare incidence over 48 weeks was a mean of 0.2, compared with 1.5 flares per person in the 48 weeks prior to treatment initiation, reported Irene E. van der Horst-Bruinsma, MD, PhD, of Amsterdam University Medical Center. The comparison was adjusted for possible within-patient correlations, flare period (pre- and post baseline), and axSpA disease duration.

This finding, from a preplanned interim analysis, represented a flare incidence of 18.7 versus 146.6 per 100 patient-years, during treatment versus prior to treatment – an 87% reduction – and the difference was statistically significant (P less than .001), Dr. van der Horst-Bruinsma said.

The percentage of patients experiencing one flare was 12.4% during therapy, compared with 64% prior to therapy, and the percentage experiencing two or more flares was 2.2% versus 24.7%, respectively, she said, adding that, in the 13 patients who experienced flares both before and during treatment, the mean flare duration was reduced during treatment (58.4 vs. 97.4 days). A comparison of radiographic and nr-axSpA patients showed similar reductions in flares during versus prior to treatment, going from 144.5 to 19.0 flares per 100 patient-years with radiographic disease and from 158.9 to 17.2 flares per 100 patient-years in nr-axSpA.

Furthermore, after 48 weeks of treatment, disease activity had improved substantially, with mean Ankylosing Spondylitis Disease Activity Score (ASDAS) improving from 3.5 to 2.0 at week 48, 94.2% of patients reaching ASDAS clinical improvement at week 48, and mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score decreasing significantly from 6.5 to 3.3 at week 48.

“ASDAS 20 was reached by 75% of the patients, the ASDAS 40 by 54%, and the ASDAS partial remission criteria were reached by 31% of the patients,” she said.

Study participants were adults with a mean age of 46.5 years and active disease according to Assessment of Spondyloarthritis International Society (ASAS) criteria and a history of recurrent AAU flares (either two or more in total, or one or more in the year prior to study entry). They were HLA-B27 positive, eligible for anti-TNF therapy because they had an inadequate response (or contraindication) to at least two prior NSAIDs, were biologic naive, or had failed to respond to no more than one prior anti-TNF agent. Both radiographic and nr-axSpA patients were included, and of 115 who enrolled, 89 initiated treatment, including 76 with radiographic disease and 13 with nonradiographic disease; 85 completed week 48 of treatment.

Certolizumab pegol was given at a loading dose of 400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks through week 96, and was well tolerated. No new safety signals were identified, Dr. van der Horst-Bruinsma said.

“We know that acute anterior uveitis, an inflammation of ... the uveal tract, is the most common extra-articular manifestation in axial spondyloarthritis,” she said. “It is reported in up to 40% of patients and is associated with significant clinical burden.”

AAU is also strongly associated with the HLA-B27 antigen, therefore patients who do not have ankylosing spondylitis but who are HLA-B27 positive also are at risk, she said, noting that previous studies have shown that TNF inhibitors reduce the incidence of AAU flares in patients with radiographic axSpA (ankylosing spondylitis), but that data in nr-axSpA are scarce.

The aim of C-VIEW was to analyze the impact of certolizumab pegol treatment on AAU flares in patients with active radiographic or nr-axSpA and a recent history of AAU, she said.

“C-VIEW was the first study to examine the impact of certolizumab on the incidence of acute anterior uveitis flares in HLA-B27-positive patients with a recent history of acute anterior uveitis, including patients with nr-axSpA ... and in conclusion we can say that these results indicate that certolizumab is a suitable treatment option for patients with axSpA and a history of recurrent acute anterior uveitis,” she said.

C-axSpAnd

In the pivotal 3-year C-axSpAnd study, which included a 52‑week, double-blind, placebo-controlled period, 159 patients with active nr-axSpA, objective signs of inflammation, and previous failure of at least two NSAIDS were treated with certolizumab pegol, and 158 similar patients received placebo. Both groups received nonbiologic background medication.

The results of the trial, published in Arthritis & Rheumatology in March 2019, showed that adding certolizumab pegol to background medication is superior to adding placebo in patients with active nr-axSpA and led to its FDA approval for axSpA in March 2019, but the effects of symptom duration on outcomes with certolizumab pegol have not been well studied, Jonathan Kay, MD, said at the ACR meeting.

The current post hoc analysis stratified patients based on symptom duration and showed that certolizumab pegol recipients with less than 5 years of symptoms at baseline had improved outcomes at weeks 12 and 52, compared with those who had 5 or more years of symptoms at baseline, said Dr. Kay of UMass Memorial Medical Center and the University of Massachusetts, Worcester.

For example, major improvement in ASDAS at week 52, the primary outcome measure, was achieved by 55% of 80 patients with shorter symptom duration, compared with 39.2% of 79 patients with longer symptom duration, and the ASAS 40 responder rates in the groups, respectively, were 58.5% and 36.7% at 12 weeks and 65% and 48.1% at 52 weeks, he said.

Certolizumab pegol recipients with shorter symptom duration also had greater improvement in BASDAI score, nocturnal spinal pain, fatigue, morning stiffness, and the 36-item Short Form Survey physical component score, he noted.

Using a cutoff of 3 years rather than 5 years, responder rates for major improvement in ASDAS and ASAS 40 were still greater in certolizumab pegol–treated patients with shorter symptom duration: At 52 weeks, 56.4% of 55 patients with less than 3 years of symptoms, compared with 42.3% of 104 with 3 or more years of symptoms, achieved major improvement in ASDAS, and ASAS 40 responder rates were 65.5%, compared with 51.9%, respectively.

Response rates in the placebo arm were low, compared with both certolizumab pegol groups, and no consistent trend in outcomes was observed based on symptom duration in that arm, Dr. Kay noted.

Study subjects were adults with a diagnosis of axSpA, active disease, fulfillment of ASAS classification criteria, and at least 12 months of inflammatory back pain. The trial excluded those with radiographic sacroiliitis meeting the modified New York classification criteria and who had exposure to more than one TNFi prior to baseline or primary failure of any TNFi. As in the C-VIEW study, participants were randomized to receive 400 mg certolizumab pegol at weeks 0, 2, and 4, and then 200 mg every 2 weeks thereafter through week 52.

The findings are notable because patients with axSpA – including radiographic disease and nr-axSpA – often experience delays in diagnosis, which can lead to a delay in treatment and a reduced quality of life because of the back pain, fatigue, and morning stiffness that commonly occur with the disease.

“Women, especially, with axial spondyloarthritis experience a longer delay in diagnosis than do male patients,” Dr. Kay noted.

The findings of this post hoc analysis underscore the risks associated with such a delay. “These results imply that early diagnosis enabling earlier treatment is important for patients with nonradiographic axSpA, as it is for patients with radiographic axSpA,” he concluded.

The C-VIEW and C-axSpAnd studies were funded by UCB. Dr. van der Horst-Bruinsma reported receiving honoraria, consulting fees, and/or research grants from UCB as well as from AbbVie, Bristol-Myers Squibb, Merck, Novartis, and Pfizer. Dr. Kay reported receiving grant/research support from Gilead, Pfizer, and UCB, and consulting fees from AbbVie, Alvotech, Boehringer Ingelheim, Celltrion, Merck, Novartis, Samsung Bioepis, Sandoz, and UCB.

[email protected]

SOURCES: van der Horst-Bruinsma I et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 935; Kay J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 936.

ATLANTA – Certolizumab pegol, a PEGylated, monoclonal, anti–tumor necrosis factor antibody, reduces recurrent acute anterior uveitis flares and improves disease activity in patients with axial spondyloarthritis, according to findings from the open-label, 96-week, phase 4 C-VIEW study.

Sharon Worcester/MDedge News

When given earlier in the course of disease, the treatment, which is the only Food and Drug Administration–approved tumor necrosis factor inhibitor (TNFi) for the treatment of nonradiographic axial spondyloarthritis (nr-axSpA), also shortens symptom duration, a post hoc analysis of data from the multicenter, phase 3 C-axSpAnd study suggests. The findings from both studies were presented during a session at the annual meeting of the American College of Rheumatology.
 

C-VIEW

In 85 patients with active axSpA who completed 48 weeks of certolizumab pegol therapy in the C-VIEW study, the acute anterior uveitis (AAU) flare incidence over 48 weeks was a mean of 0.2, compared with 1.5 flares per person in the 48 weeks prior to treatment initiation, reported Irene E. van der Horst-Bruinsma, MD, PhD, of Amsterdam University Medical Center. The comparison was adjusted for possible within-patient correlations, flare period (pre- and post baseline), and axSpA disease duration.

This finding, from a preplanned interim analysis, represented a flare incidence of 18.7 versus 146.6 per 100 patient-years, during treatment versus prior to treatment – an 87% reduction – and the difference was statistically significant (P less than .001), Dr. van der Horst-Bruinsma said.

The percentage of patients experiencing one flare was 12.4% during therapy, compared with 64% prior to therapy, and the percentage experiencing two or more flares was 2.2% versus 24.7%, respectively, she said, adding that, in the 13 patients who experienced flares both before and during treatment, the mean flare duration was reduced during treatment (58.4 vs. 97.4 days). A comparison of radiographic and nr-axSpA patients showed similar reductions in flares during versus prior to treatment, going from 144.5 to 19.0 flares per 100 patient-years with radiographic disease and from 158.9 to 17.2 flares per 100 patient-years in nr-axSpA.

Furthermore, after 48 weeks of treatment, disease activity had improved substantially, with mean Ankylosing Spondylitis Disease Activity Score (ASDAS) improving from 3.5 to 2.0 at week 48, 94.2% of patients reaching ASDAS clinical improvement at week 48, and mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score decreasing significantly from 6.5 to 3.3 at week 48.

“ASDAS 20 was reached by 75% of the patients, the ASDAS 40 by 54%, and the ASDAS partial remission criteria were reached by 31% of the patients,” she said.

Study participants were adults with a mean age of 46.5 years and active disease according to Assessment of Spondyloarthritis International Society (ASAS) criteria and a history of recurrent AAU flares (either two or more in total, or one or more in the year prior to study entry). They were HLA-B27 positive, eligible for anti-TNF therapy because they had an inadequate response (or contraindication) to at least two prior NSAIDs, were biologic naive, or had failed to respond to no more than one prior anti-TNF agent. Both radiographic and nr-axSpA patients were included, and of 115 who enrolled, 89 initiated treatment, including 76 with radiographic disease and 13 with nonradiographic disease; 85 completed week 48 of treatment.

Certolizumab pegol was given at a loading dose of 400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks through week 96, and was well tolerated. No new safety signals were identified, Dr. van der Horst-Bruinsma said.

“We know that acute anterior uveitis, an inflammation of ... the uveal tract, is the most common extra-articular manifestation in axial spondyloarthritis,” she said. “It is reported in up to 40% of patients and is associated with significant clinical burden.”

AAU is also strongly associated with the HLA-B27 antigen, therefore patients who do not have ankylosing spondylitis but who are HLA-B27 positive also are at risk, she said, noting that previous studies have shown that TNF inhibitors reduce the incidence of AAU flares in patients with radiographic axSpA (ankylosing spondylitis), but that data in nr-axSpA are scarce.

The aim of C-VIEW was to analyze the impact of certolizumab pegol treatment on AAU flares in patients with active radiographic or nr-axSpA and a recent history of AAU, she said.

“C-VIEW was the first study to examine the impact of certolizumab on the incidence of acute anterior uveitis flares in HLA-B27-positive patients with a recent history of acute anterior uveitis, including patients with nr-axSpA ... and in conclusion we can say that these results indicate that certolizumab is a suitable treatment option for patients with axSpA and a history of recurrent acute anterior uveitis,” she said.

C-axSpAnd

In the pivotal 3-year C-axSpAnd study, which included a 52‑week, double-blind, placebo-controlled period, 159 patients with active nr-axSpA, objective signs of inflammation, and previous failure of at least two NSAIDS were treated with certolizumab pegol, and 158 similar patients received placebo. Both groups received nonbiologic background medication.

The results of the trial, published in Arthritis & Rheumatology in March 2019, showed that adding certolizumab pegol to background medication is superior to adding placebo in patients with active nr-axSpA and led to its FDA approval for axSpA in March 2019, but the effects of symptom duration on outcomes with certolizumab pegol have not been well studied, Jonathan Kay, MD, said at the ACR meeting.

The current post hoc analysis stratified patients based on symptom duration and showed that certolizumab pegol recipients with less than 5 years of symptoms at baseline had improved outcomes at weeks 12 and 52, compared with those who had 5 or more years of symptoms at baseline, said Dr. Kay of UMass Memorial Medical Center and the University of Massachusetts, Worcester.

For example, major improvement in ASDAS at week 52, the primary outcome measure, was achieved by 55% of 80 patients with shorter symptom duration, compared with 39.2% of 79 patients with longer symptom duration, and the ASAS 40 responder rates in the groups, respectively, were 58.5% and 36.7% at 12 weeks and 65% and 48.1% at 52 weeks, he said.

Certolizumab pegol recipients with shorter symptom duration also had greater improvement in BASDAI score, nocturnal spinal pain, fatigue, morning stiffness, and the 36-item Short Form Survey physical component score, he noted.

Using a cutoff of 3 years rather than 5 years, responder rates for major improvement in ASDAS and ASAS 40 were still greater in certolizumab pegol–treated patients with shorter symptom duration: At 52 weeks, 56.4% of 55 patients with less than 3 years of symptoms, compared with 42.3% of 104 with 3 or more years of symptoms, achieved major improvement in ASDAS, and ASAS 40 responder rates were 65.5%, compared with 51.9%, respectively.

Response rates in the placebo arm were low, compared with both certolizumab pegol groups, and no consistent trend in outcomes was observed based on symptom duration in that arm, Dr. Kay noted.

Study subjects were adults with a diagnosis of axSpA, active disease, fulfillment of ASAS classification criteria, and at least 12 months of inflammatory back pain. The trial excluded those with radiographic sacroiliitis meeting the modified New York classification criteria and who had exposure to more than one TNFi prior to baseline or primary failure of any TNFi. As in the C-VIEW study, participants were randomized to receive 400 mg certolizumab pegol at weeks 0, 2, and 4, and then 200 mg every 2 weeks thereafter through week 52.

The findings are notable because patients with axSpA – including radiographic disease and nr-axSpA – often experience delays in diagnosis, which can lead to a delay in treatment and a reduced quality of life because of the back pain, fatigue, and morning stiffness that commonly occur with the disease.

“Women, especially, with axial spondyloarthritis experience a longer delay in diagnosis than do male patients,” Dr. Kay noted.

The findings of this post hoc analysis underscore the risks associated with such a delay. “These results imply that early diagnosis enabling earlier treatment is important for patients with nonradiographic axSpA, as it is for patients with radiographic axSpA,” he concluded.

The C-VIEW and C-axSpAnd studies were funded by UCB. Dr. van der Horst-Bruinsma reported receiving honoraria, consulting fees, and/or research grants from UCB as well as from AbbVie, Bristol-Myers Squibb, Merck, Novartis, and Pfizer. Dr. Kay reported receiving grant/research support from Gilead, Pfizer, and UCB, and consulting fees from AbbVie, Alvotech, Boehringer Ingelheim, Celltrion, Merck, Novartis, Samsung Bioepis, Sandoz, and UCB.

[email protected]

SOURCES: van der Horst-Bruinsma I et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 935; Kay J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 936.

ATLANTA – Upadacitinib (Rinvoq), a selective Janus kinase 1 (JAK1) inhibitor, significantly improved the signs and symptoms of active ankylosing spondylitis, compared with placebo, in the randomized, placebo-controlled, phase 2/3 SELECT-AXIS 1 study.

Physical functioning and imaging measures also were improved with upadacitinib in the double-blind, multicenter study, Désirée van der Heijde, MD, PhD, reported at the annual meeting of the American College of Rheumatology.

The findings are notable because patients with ankylosing spondylitis (AS) who have an inadequate response or contraindication to NSAIDs have limited treatment options other than biologic disease-modifying antirheumatic drugs (bDMARDs). The JAK pathway has emerged as a potential therapeutic target in AS, and given its recent approval for the treatment of RA as well as ongoing studies of the agent for several other chronic immune-mediated inflammatory diseases, Dr. van der Heijde and colleagues sought to assess its efficacy and safety in bDMARD-naive patients with active AS.

Of 93 AS patients aged 18 years and older who were randomized to receive 15 mg of upadacitinib daily, 51.6% achieved the primary study endpoint of 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40) at week 14, compared with 25.5% of 94 patients who received placebo, said Dr. van der Heijde, professor of rheumatology at Leiden (the Netherlands) University Medical Center.

The effect was rapid, with a clear difference emerging between the treatment and placebo groups within 2 weeks, she noted.

Significant improvements were also seen with upadacitinib for several key secondary endpoints including change from baseline to week 14 in the Ankylosing Spondylitis Disease Activity Score, Spondyloarthritis Research Consortium of Canada MRI Spine, a 50% improvement of the initial Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50), ASAS partial remission, and Bath Ankylosing Spondylitis Functional Index.

SELECT-AXIS 1 patients were adults with a mean age of 45 years who were enrolled from 60 sites in 20 countries. All met modified New York criteria for AS based on central reading of radiographs, had a BASDAI score of at least 4, had a patient assessment of total back pain of 4 or greater on a 0-10 scale at screening and baseline, were naive to bDMARDs, and had either an inadequate response to at least two NSAIDs or an intolerance/contraindication to NSAIDs.

Most patients (70.6%) were men, and 76.5% were HLA-B27 positive. Mean symptom duration was 14-15 years, and mean disease duration was 7-8 years, Dr. van der Heijde said, adding that baseline disease characteristics were balanced between the two arms.

All randomized patients received their assigned treatment, and 95.7% completed the study through week 14, including 90 of 94 placebo group patients and 89 of 93 upadacitinib patients.

“Treatment was generally well tolerated,” she said.

The proportions of patients in the treatment and placebo groups, respectively, were similar with respect to adverse events leading to discontinuation (2.2% vs. 3.2%), serious adverse events (1.1% in each group), and infections (20.4% vs. 27.7%). No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported. Also, no differences were seen between the groups in relevant laboratory abnormalities, and no new safety finding were observed in comparison with previous upadacitinib studies in other diseases, she noted.

Dr. van der Heijde concluded that “these results support further investigation of upadacitinib for the treatment of ankylosing spondyloarthritis.”

AbbVie, which markets upadacitinib, funded the study. Dr. van der Heijde disclosed financial relationships with AbbVie and 20 other pharmaceutical companies. Many other authors also reported financial relationships with industry, including AbbVie.

[email protected]

SOURCE: van der Heijde D et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2728.

ATLANTA – Upadacitinib (Rinvoq), a selective Janus kinase 1 (JAK1) inhibitor, significantly improved the signs and symptoms of active ankylosing spondylitis, compared with placebo, in the randomized, placebo-controlled, phase 2/3 SELECT-AXIS 1 study.

Physical functioning and imaging measures also were improved with upadacitinib in the double-blind, multicenter study, Désirée van der Heijde, MD, PhD, reported at the annual meeting of the American College of Rheumatology.

The findings are notable because patients with ankylosing spondylitis (AS) who have an inadequate response or contraindication to NSAIDs have limited treatment options other than biologic disease-modifying antirheumatic drugs (bDMARDs). The JAK pathway has emerged as a potential therapeutic target in AS, and given its recent approval for the treatment of RA as well as ongoing studies of the agent for several other chronic immune-mediated inflammatory diseases, Dr. van der Heijde and colleagues sought to assess its efficacy and safety in bDMARD-naive patients with active AS.

Of 93 AS patients aged 18 years and older who were randomized to receive 15 mg of upadacitinib daily, 51.6% achieved the primary study endpoint of 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40) at week 14, compared with 25.5% of 94 patients who received placebo, said Dr. van der Heijde, professor of rheumatology at Leiden (the Netherlands) University Medical Center.

The effect was rapid, with a clear difference emerging between the treatment and placebo groups within 2 weeks, she noted.

Significant improvements were also seen with upadacitinib for several key secondary endpoints including change from baseline to week 14 in the Ankylosing Spondylitis Disease Activity Score, Spondyloarthritis Research Consortium of Canada MRI Spine, a 50% improvement of the initial Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50), ASAS partial remission, and Bath Ankylosing Spondylitis Functional Index.

SELECT-AXIS 1 patients were adults with a mean age of 45 years who were enrolled from 60 sites in 20 countries. All met modified New York criteria for AS based on central reading of radiographs, had a BASDAI score of at least 4, had a patient assessment of total back pain of 4 or greater on a 0-10 scale at screening and baseline, were naive to bDMARDs, and had either an inadequate response to at least two NSAIDs or an intolerance/contraindication to NSAIDs.

Most patients (70.6%) were men, and 76.5% were HLA-B27 positive. Mean symptom duration was 14-15 years, and mean disease duration was 7-8 years, Dr. van der Heijde said, adding that baseline disease characteristics were balanced between the two arms.

All randomized patients received their assigned treatment, and 95.7% completed the study through week 14, including 90 of 94 placebo group patients and 89 of 93 upadacitinib patients.

“Treatment was generally well tolerated,” she said.

The proportions of patients in the treatment and placebo groups, respectively, were similar with respect to adverse events leading to discontinuation (2.2% vs. 3.2%), serious adverse events (1.1% in each group), and infections (20.4% vs. 27.7%). No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported. Also, no differences were seen between the groups in relevant laboratory abnormalities, and no new safety finding were observed in comparison with previous upadacitinib studies in other diseases, she noted.

Dr. van der Heijde concluded that “these results support further investigation of upadacitinib for the treatment of ankylosing spondyloarthritis.”

AbbVie, which markets upadacitinib, funded the study. Dr. van der Heijde disclosed financial relationships with AbbVie and 20 other pharmaceutical companies. Many other authors also reported financial relationships with industry, including AbbVie.

[email protected]

SOURCE: van der Heijde D et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2728.

ATLANTA – Upadacitinib (Rinvoq), a selective Janus kinase 1 (JAK1) inhibitor, significantly improved the signs and symptoms of active ankylosing spondylitis, compared with placebo, in the randomized, placebo-controlled, phase 2/3 SELECT-AXIS 1 study.

Physical functioning and imaging measures also were improved with upadacitinib in the double-blind, multicenter study, Désirée van der Heijde, MD, PhD, reported at the annual meeting of the American College of Rheumatology.

The findings are notable because patients with ankylosing spondylitis (AS) who have an inadequate response or contraindication to NSAIDs have limited treatment options other than biologic disease-modifying antirheumatic drugs (bDMARDs). The JAK pathway has emerged as a potential therapeutic target in AS, and given its recent approval for the treatment of RA as well as ongoing studies of the agent for several other chronic immune-mediated inflammatory diseases, Dr. van der Heijde and colleagues sought to assess its efficacy and safety in bDMARD-naive patients with active AS.

Of 93 AS patients aged 18 years and older who were randomized to receive 15 mg of upadacitinib daily, 51.6% achieved the primary study endpoint of 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40) at week 14, compared with 25.5% of 94 patients who received placebo, said Dr. van der Heijde, professor of rheumatology at Leiden (the Netherlands) University Medical Center.

The effect was rapid, with a clear difference emerging between the treatment and placebo groups within 2 weeks, she noted.

Significant improvements were also seen with upadacitinib for several key secondary endpoints including change from baseline to week 14 in the Ankylosing Spondylitis Disease Activity Score, Spondyloarthritis Research Consortium of Canada MRI Spine, a 50% improvement of the initial Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50), ASAS partial remission, and Bath Ankylosing Spondylitis Functional Index.

SELECT-AXIS 1 patients were adults with a mean age of 45 years who were enrolled from 60 sites in 20 countries. All met modified New York criteria for AS based on central reading of radiographs, had a BASDAI score of at least 4, had a patient assessment of total back pain of 4 or greater on a 0-10 scale at screening and baseline, were naive to bDMARDs, and had either an inadequate response to at least two NSAIDs or an intolerance/contraindication to NSAIDs.

Most patients (70.6%) were men, and 76.5% were HLA-B27 positive. Mean symptom duration was 14-15 years, and mean disease duration was 7-8 years, Dr. van der Heijde said, adding that baseline disease characteristics were balanced between the two arms.

All randomized patients received their assigned treatment, and 95.7% completed the study through week 14, including 90 of 94 placebo group patients and 89 of 93 upadacitinib patients.

“Treatment was generally well tolerated,” she said.

The proportions of patients in the treatment and placebo groups, respectively, were similar with respect to adverse events leading to discontinuation (2.2% vs. 3.2%), serious adverse events (1.1% in each group), and infections (20.4% vs. 27.7%). No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported. Also, no differences were seen between the groups in relevant laboratory abnormalities, and no new safety finding were observed in comparison with previous upadacitinib studies in other diseases, she noted.

Dr. van der Heijde concluded that “these results support further investigation of upadacitinib for the treatment of ankylosing spondyloarthritis.”

AbbVie, which markets upadacitinib, funded the study. Dr. van der Heijde disclosed financial relationships with AbbVie and 20 other pharmaceutical companies. Many other authors also reported financial relationships with industry, including AbbVie.

[email protected]

SOURCE: van der Heijde D et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2728.

MADRID – The risk of serious adverse events in patients on certolizumab varies considerably across indications for use of the biologic, with differential disease-related rates of systemic corticosteroid use and obesity having a big impact, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

He presented a comprehensive analysis of safety data from all 49 clinical trials of the tumor necrosis factor inhibitor for its approved indications. The data set included 11,317 patients who received certolizumab for a collective 21,695 person-years in 27 trials in rheumatoid arthritis patients, 5 in psoriasis, 15 for Crohn’s disease, and one trial each for axial spondyloarthritis and psoriatic arthritis.

“It’s not real-world data, but it is a large group of patients [studied] over many years,” noted Dr. Blauvelt, a dermatologist and president of the Oregon Medical Research Center, Portland.

As a renowned authority on psoriasis, he was part of a multidisciplinary expert panel commissioned by UCB to analyze serious adverse events in the complete clinical trials experience involving the company’s tumor necrosis factor inhibitor certolizumab (Cimzia). The panel included experts from rheumatology, gastroenterology, epidemiology, and other disciplines.

The key takeaway: “When you think about the serious side effects of the drug, you have to think about what the indication is, whether the patients are on systemic corticosteroids, and whether they’re heavy or not,” Dr. Blauvelt said.

Take, for example, the risk of serious infections requiring treatment with intravenous antibiotics. The incidence rates ranged from a low of 1.5 per 100 patient-years in psoriasis patients on certolizumab to a high of 5.97 in those with Crohn’s disease, with rates of 3.44 cases per 100 patient-years among rheumatoid arthritis patients and 1.64-1.67 in those with psoriatic arthritis and ankylosing spondylitis, respectively. Patients with Crohn’s disease were 2.22-fold more likely than were those with rheumatoid arthritis to experience a serious infection during their clinical trial experience on certolizumab. In contrast, psoriasis patients had a 52% relative risk reduction and those with psoriatic arthritis were 31% less likely to develop a serious infection compared with those with rheumatoid arthritis.

The explanation for these highly variable serious infection rates lies in part on the huge differences in the concurrent use of systemic corticosteroids with certolizumab across indications. A mere 3.3% of psoriasis patients were also on steroids, compared with 46.2% of rheumatoid arthritis patients, 50.8% of those with ankylosing spondylitis, and about 25% of the Crohn’s disease and psoriatic arthritis patients, he noted.

Advanced age was independently associated with increased risk of serious infections. Patients aged 65 or older were 1.68-fold more likely to experience this event than were those under age 45. And patients whose disease duration was 10 years or more at baseline had a 1.36-fold increased serious infection risk compared with those who had less than a 1-year-long disease history, independent of which disease they had.

The prevalence of baseline obesity varied by indication. The mean body mass index was 30.1 kg/m² in the psoriasis patients, 29.8 kg/m² in those with psoriatic arthritis, lowest at 24 kg/m² in Crohn’s disease patients, and a bit over 27 kg/m² in those with rheumatoid arthritis or ankylosing spondylitis.

Obesity alone was not an independent risk factor for serious infection in certolizumab-treated patients; however, the combination of a BMI of 30 kg/m² or more plus systemic corticosteroid use was associated with a greater risk than with steroids alone.

Based upon a multivariate regression analysis adjusted for age, sex, indication, disease duration, use of methotrexate, and prior use of other TNF inhibitors, the investigators calculated that in patients with Crohn’s disease 16.6% of serious infections in patients on certolizumab were attributable to systemic corticosteroid use.
 

Risks of major adverse cardiovascular events and cancer on certolizumab

The risk of major adverse cardiovascular events (MACE) while on certolizumab ranged from a high of 0.62 MACE events per 100 patient-years in the rheumatoid arthritis population to a low of 0.1 per 100 patient-years in patients treated for Crohn’s disease or ankylosing spondylitis. Psoriasis and psoriatic arthritis patients had MACE rates of 0.27 and 0.54, respectively.

Obesity was independently associated with increased risk of an acute MI and other MACEs. So was advanced age. No surprises there. The investigators calculated that 16.7% of MACEs in patients on certolizumab were attributable to obesity and another 20.9% were attributable to use of systemic corticosteroids.

The incidence rate for all malignancies, including nonmelanoma skin cancer, ranged from a low of 0.46 cases per 100 patient-years in the psoriatic arthritis cohort on certolizumab to a high of 0.93 in those with rheumatoid arthritis, with rates of 0.68, 0.73, and 0.51 in patients with psoriasis, Crohn’s disease, and ankylosing spondylitis, respectively.

Neither systemic corticosteroids, obesity, disease duration, or prior exposure to a TNF inhibitor was linked to increased risk of cancer in patients on certolizumab. The standout risk factor was age: Patients who were 65 or older at baseline were 11.4-fold more likely to develop cancer during participation in their clinical trial than were those younger than 45. Those who were 45 to 65 years old were 4.3-fold more likely to be diagnosed with a malignancy than were those younger than age 45.

Of note, concomitant use of methotrexate was associated with a statistically significant 28% reduction in malignancy risk.

Dr. Blauvelt reported serving as a consultant to and receiving research funding from UCB, the study sponsor, as well as more than two dozen other pharmaceutical companies.

[email protected]

SOURCE: Blauvelt A. EADV Congress, Abstract FC04.06.

MADRID – The risk of serious adverse events in patients on certolizumab varies considerably across indications for use of the biologic, with differential disease-related rates of systemic corticosteroid use and obesity having a big impact, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

He presented a comprehensive analysis of safety data from all 49 clinical trials of the tumor necrosis factor inhibitor for its approved indications. The data set included 11,317 patients who received certolizumab for a collective 21,695 person-years in 27 trials in rheumatoid arthritis patients, 5 in psoriasis, 15 for Crohn’s disease, and one trial each for axial spondyloarthritis and psoriatic arthritis.

“It’s not real-world data, but it is a large group of patients [studied] over many years,” noted Dr. Blauvelt, a dermatologist and president of the Oregon Medical Research Center, Portland.

As a renowned authority on psoriasis, he was part of a multidisciplinary expert panel commissioned by UCB to analyze serious adverse events in the complete clinical trials experience involving the company’s tumor necrosis factor inhibitor certolizumab (Cimzia). The panel included experts from rheumatology, gastroenterology, epidemiology, and other disciplines.

The key takeaway: “When you think about the serious side effects of the drug, you have to think about what the indication is, whether the patients are on systemic corticosteroids, and whether they’re heavy or not,” Dr. Blauvelt said.

Take, for example, the risk of serious infections requiring treatment with intravenous antibiotics. The incidence rates ranged from a low of 1.5 per 100 patient-years in psoriasis patients on certolizumab to a high of 5.97 in those with Crohn’s disease, with rates of 3.44 cases per 100 patient-years among rheumatoid arthritis patients and 1.64-1.67 in those with psoriatic arthritis and ankylosing spondylitis, respectively. Patients with Crohn’s disease were 2.22-fold more likely than were those with rheumatoid arthritis to experience a serious infection during their clinical trial experience on certolizumab. In contrast, psoriasis patients had a 52% relative risk reduction and those with psoriatic arthritis were 31% less likely to develop a serious infection compared with those with rheumatoid arthritis.

The explanation for these highly variable serious infection rates lies in part on the huge differences in the concurrent use of systemic corticosteroids with certolizumab across indications. A mere 3.3% of psoriasis patients were also on steroids, compared with 46.2% of rheumatoid arthritis patients, 50.8% of those with ankylosing spondylitis, and about 25% of the Crohn’s disease and psoriatic arthritis patients, he noted.

Advanced age was independently associated with increased risk of serious infections. Patients aged 65 or older were 1.68-fold more likely to experience this event than were those under age 45. And patients whose disease duration was 10 years or more at baseline had a 1.36-fold increased serious infection risk compared with those who had less than a 1-year-long disease history, independent of which disease they had.

The prevalence of baseline obesity varied by indication. The mean body mass index was 30.1 kg/m² in the psoriasis patients, 29.8 kg/m² in those with psoriatic arthritis, lowest at 24 kg/m² in Crohn’s disease patients, and a bit over 27 kg/m² in those with rheumatoid arthritis or ankylosing spondylitis.

Obesity alone was not an independent risk factor for serious infection in certolizumab-treated patients; however, the combination of a BMI of 30 kg/m² or more plus systemic corticosteroid use was associated with a greater risk than with steroids alone.

Based upon a multivariate regression analysis adjusted for age, sex, indication, disease duration, use of methotrexate, and prior use of other TNF inhibitors, the investigators calculated that in patients with Crohn’s disease 16.6% of serious infections in patients on certolizumab were attributable to systemic corticosteroid use.
 

Risks of major adverse cardiovascular events and cancer on certolizumab

The risk of major adverse cardiovascular events (MACE) while on certolizumab ranged from a high of 0.62 MACE events per 100 patient-years in the rheumatoid arthritis population to a low of 0.1 per 100 patient-years in patients treated for Crohn’s disease or ankylosing spondylitis. Psoriasis and psoriatic arthritis patients had MACE rates of 0.27 and 0.54, respectively.

Obesity was independently associated with increased risk of an acute MI and other MACEs. So was advanced age. No surprises there. The investigators calculated that 16.7% of MACEs in patients on certolizumab were attributable to obesity and another 20.9% were attributable to use of systemic corticosteroids.

The incidence rate for all malignancies, including nonmelanoma skin cancer, ranged from a low of 0.46 cases per 100 patient-years in the psoriatic arthritis cohort on certolizumab to a high of 0.93 in those with rheumatoid arthritis, with rates of 0.68, 0.73, and 0.51 in patients with psoriasis, Crohn’s disease, and ankylosing spondylitis, respectively.

Neither systemic corticosteroids, obesity, disease duration, or prior exposure to a TNF inhibitor was linked to increased risk of cancer in patients on certolizumab. The standout risk factor was age: Patients who were 65 or older at baseline were 11.4-fold more likely to develop cancer during participation in their clinical trial than were those younger than 45. Those who were 45 to 65 years old were 4.3-fold more likely to be diagnosed with a malignancy than were those younger than age 45.

Of note, concomitant use of methotrexate was associated with a statistically significant 28% reduction in malignancy risk.

Dr. Blauvelt reported serving as a consultant to and receiving research funding from UCB, the study sponsor, as well as more than two dozen other pharmaceutical companies.

[email protected]

SOURCE: Blauvelt A. EADV Congress, Abstract FC04.06.

MADRID – The risk of serious adverse events in patients on certolizumab varies considerably across indications for use of the biologic, with differential disease-related rates of systemic corticosteroid use and obesity having a big impact, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

He presented a comprehensive analysis of safety data from all 49 clinical trials of the tumor necrosis factor inhibitor for its approved indications. The data set included 11,317 patients who received certolizumab for a collective 21,695 person-years in 27 trials in rheumatoid arthritis patients, 5 in psoriasis, 15 for Crohn’s disease, and one trial each for axial spondyloarthritis and psoriatic arthritis.

“It’s not real-world data, but it is a large group of patients [studied] over many years,” noted Dr. Blauvelt, a dermatologist and president of the Oregon Medical Research Center, Portland.

As a renowned authority on psoriasis, he was part of a multidisciplinary expert panel commissioned by UCB to analyze serious adverse events in the complete clinical trials experience involving the company’s tumor necrosis factor inhibitor certolizumab (Cimzia). The panel included experts from rheumatology, gastroenterology, epidemiology, and other disciplines.

The key takeaway: “When you think about the serious side effects of the drug, you have to think about what the indication is, whether the patients are on systemic corticosteroids, and whether they’re heavy or not,” Dr. Blauvelt said.

Take, for example, the risk of serious infections requiring treatment with intravenous antibiotics. The incidence rates ranged from a low of 1.5 per 100 patient-years in psoriasis patients on certolizumab to a high of 5.97 in those with Crohn’s disease, with rates of 3.44 cases per 100 patient-years among rheumatoid arthritis patients and 1.64-1.67 in those with psoriatic arthritis and ankylosing spondylitis, respectively. Patients with Crohn’s disease were 2.22-fold more likely than were those with rheumatoid arthritis to experience a serious infection during their clinical trial experience on certolizumab. In contrast, psoriasis patients had a 52% relative risk reduction and those with psoriatic arthritis were 31% less likely to develop a serious infection compared with those with rheumatoid arthritis.

The explanation for these highly variable serious infection rates lies in part on the huge differences in the concurrent use of systemic corticosteroids with certolizumab across indications. A mere 3.3% of psoriasis patients were also on steroids, compared with 46.2% of rheumatoid arthritis patients, 50.8% of those with ankylosing spondylitis, and about 25% of the Crohn’s disease and psoriatic arthritis patients, he noted.

Advanced age was independently associated with increased risk of serious infections. Patients aged 65 or older were 1.68-fold more likely to experience this event than were those under age 45. And patients whose disease duration was 10 years or more at baseline had a 1.36-fold increased serious infection risk compared with those who had less than a 1-year-long disease history, independent of which disease they had.

The prevalence of baseline obesity varied by indication. The mean body mass index was 30.1 kg/m² in the psoriasis patients, 29.8 kg/m² in those with psoriatic arthritis, lowest at 24 kg/m² in Crohn’s disease patients, and a bit over 27 kg/m² in those with rheumatoid arthritis or ankylosing spondylitis.

Obesity alone was not an independent risk factor for serious infection in certolizumab-treated patients; however, the combination of a BMI of 30 kg/m² or more plus systemic corticosteroid use was associated with a greater risk than with steroids alone.

Based upon a multivariate regression analysis adjusted for age, sex, indication, disease duration, use of methotrexate, and prior use of other TNF inhibitors, the investigators calculated that in patients with Crohn’s disease 16.6% of serious infections in patients on certolizumab were attributable to systemic corticosteroid use.
 

Risks of major adverse cardiovascular events and cancer on certolizumab

The risk of major adverse cardiovascular events (MACE) while on certolizumab ranged from a high of 0.62 MACE events per 100 patient-years in the rheumatoid arthritis population to a low of 0.1 per 100 patient-years in patients treated for Crohn’s disease or ankylosing spondylitis. Psoriasis and psoriatic arthritis patients had MACE rates of 0.27 and 0.54, respectively.

Obesity was independently associated with increased risk of an acute MI and other MACEs. So was advanced age. No surprises there. The investigators calculated that 16.7% of MACEs in patients on certolizumab were attributable to obesity and another 20.9% were attributable to use of systemic corticosteroids.

The incidence rate for all malignancies, including nonmelanoma skin cancer, ranged from a low of 0.46 cases per 100 patient-years in the psoriatic arthritis cohort on certolizumab to a high of 0.93 in those with rheumatoid arthritis, with rates of 0.68, 0.73, and 0.51 in patients with psoriasis, Crohn’s disease, and ankylosing spondylitis, respectively.

Neither systemic corticosteroids, obesity, disease duration, or prior exposure to a TNF inhibitor was linked to increased risk of cancer in patients on certolizumab. The standout risk factor was age: Patients who were 65 or older at baseline were 11.4-fold more likely to develop cancer during participation in their clinical trial than were those younger than 45. Those who were 45 to 65 years old were 4.3-fold more likely to be diagnosed with a malignancy than were those younger than age 45.

Of note, concomitant use of methotrexate was associated with a statistically significant 28% reduction in malignancy risk.

Dr. Blauvelt reported serving as a consultant to and receiving research funding from UCB, the study sponsor, as well as more than two dozen other pharmaceutical companies.

[email protected]

SOURCE: Blauvelt A. EADV Congress, Abstract FC04.06.

The VERVE study highlights a crucial topic for rheumatologists treating patients in clinical practice. The traditional thinking is to inform patients never to receive live vaccines when they are using TNF (tumor necrosis factor) inhibitors to treat their autoimmune disease. The VERVE study indicates that in the case of the Zostavax vaccine, patients on this form of biologic therapy for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis can safely receive this preventive measure. This study scratches the surface on an important topic, and other studies need to follow.

Many patients on biologic therapy want to travel. Many times, international travel requires vaccination that is only in the form of a live vaccine – for example, the yellow fever vaccine. It would be useful for us to better understand whether other live vaccines can safely be administered and better inform our patients who want to travel. In addition, many times mothers with young infants are nervous if they are on biologic therapy and their children need to receive a live vaccine. They are concerned that their children will shed the live virus and they will be in jeopardy. This study highlights that this may be more of an antiquated way of thinking. We need more studies of this kind to better understand and advise our patients properly without instilling unwarranted fear.

Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.

The VERVE study highlights a crucial topic for rheumatologists treating patients in clinical practice. The traditional thinking is to inform patients never to receive live vaccines when they are using TNF (tumor necrosis factor) inhibitors to treat their autoimmune disease. The VERVE study indicates that in the case of the Zostavax vaccine, patients on this form of biologic therapy for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis can safely receive this preventive measure. This study scratches the surface on an important topic, and other studies need to follow.

Many patients on biologic therapy want to travel. Many times, international travel requires vaccination that is only in the form of a live vaccine – for example, the yellow fever vaccine. It would be useful for us to better understand whether other live vaccines can safely be administered and better inform our patients who want to travel. In addition, many times mothers with young infants are nervous if they are on biologic therapy and their children need to receive a live vaccine. They are concerned that their children will shed the live virus and they will be in jeopardy. This study highlights that this may be more of an antiquated way of thinking. We need more studies of this kind to better understand and advise our patients properly without instilling unwarranted fear.

Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.

The VERVE study highlights a crucial topic for rheumatologists treating patients in clinical practice. The traditional thinking is to inform patients never to receive live vaccines when they are using TNF (tumor necrosis factor) inhibitors to treat their autoimmune disease. The VERVE study indicates that in the case of the Zostavax vaccine, patients on this form of biologic therapy for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis can safely receive this preventive measure. This study scratches the surface on an important topic, and other studies need to follow.

Many patients on biologic therapy want to travel. Many times, international travel requires vaccination that is only in the form of a live vaccine – for example, the yellow fever vaccine. It would be useful for us to better understand whether other live vaccines can safely be administered and better inform our patients who want to travel. In addition, many times mothers with young infants are nervous if they are on biologic therapy and their children need to receive a live vaccine. They are concerned that their children will shed the live virus and they will be in jeopardy. This study highlights that this may be more of an antiquated way of thinking. We need more studies of this kind to better understand and advise our patients properly without instilling unwarranted fear.

Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.