Evidence builds for biologics’ effect on height, disease activity in JIA patients

LIVERPOOL, ENGLAND – Biologic therapy has shown sustained benefits for the signs and symptoms of juvenile idiopathic arthritis as well as improved height over the course of up to 2 years of treatment, according to data from four studies presented at the British Society for Rheumatology annual conference.

The studies provided evidence indicating that:

• Treatment with etanercept over 2 years helped children with juvenile idiopathic arthritis (JIA) to gain height, although their overall vertical growth still lagged behind children in the general reference population.

• When etanercept was not used as a first-line biologic, it was most common to use adalimumab instead, followed by tocilizumab and infliximab.

• Adalimumab reduced the signs and symptoms of enthesitis-related arthritis (ERA) in children by week 12 of treatment and the effects were sustained at 1-year of follow up.

• The benefits of tocilizumab in reducing disease activity to a minimal level were preserved from 40 weeks to 2 years in most patients.

Etanercept and growth in JIA

"Etanercept therapy was associated with improvement in height z score over the first 2 years of therapy," and the effect was most apparent in children who were not receiving concomitant steroids, said Lianne Kearsley-Fleet, who reported data from the British Society for Paediatric and Adolescent Rheumatology (BSPAR Etanercept Cohort Study). The prospective, observational study was initiated in 2004 with the aim of recruiting all children with JIA who were starting treatment with etanercept. For comparison, a cohort of children newly starting methotrexate was also included.

The current analysis focused on the growth of children taking the biologic therapy because children with JIA are known to have restricted growth, which may be linked to inflammation and the use of corticosteroids. Of 658 children registered in the study, 191 had height data available at baseline and at 1 and 2 years’ follow-up.

Mean height and changes in height during biologic therapy over time were assessed by calculating z scores, and compared with values set by the World Health Organization for girls and boys of a similar age who did not have JIA.

The mean age of children included in the current analysis was 11 years, with a mean disease duration of 3.5 years. The majority (65%) were female, with concomitant oral steroids in 38% and methotrexate in 58%.

The mean height z score of the study population was –0.67 at baseline, –0.57 after 1 year, and –0.45 after 2 years’ etanercept therapy. "While it is still negative [compared with children of a similar sex and age], there is still significant improvement," said Ms. Kearsley-Fleet, a research assistant from the Arthritis Research UK Centre for Epidemiology at the University of Manchester, England.

"There was a lack of evidence for association between disease activity and improved growth," the researcher noted, adding that "anti-TNF inhibitors alone may be insufficient to increase growth."

Use of non–etanercept biologics

In a poster presentation at the meeting, Ms. Kearsley-Fleet and her colleagues at her institution also presented the findings from the Biologics for Children with Rheumatic Diseases Study. This ongoing, prospective, observational cohort study is looking at the use of biologics other than etanercept in the treatment of JIA.

Since the study started in 2010, and up until early April 2014, a total of 280 children with JIA had been recruited into the biologic cohort. The study also includes a parallel control cohort of 295 children being treated with methotrexate. Just under half (46%) of the children recruited into the biologic cohort started a non–etanercept biologic as their first biologic treatment, of which the majority (75%) received the medications off label. The main alternatives to etanercept being used were adalimumab in 38% of cases, followed by tocilizumab in 25% of children, and infliximab in 23%. Other drugs used as the first biologic was anakinra (13%), rituximab (less than 1%), and abatacept (less than 1%).

Adalimumab was also a popular subsequent biologic choice in 30% of cases, with 20% of patients using tocilizumab, and 25% infliximab as a subsequent biologic choice.

The research team reported that patients using a biologic for the first time were significantly younger and had shorter disease durations than did subsequent biologic users. The mean ages of first-, second-, and third-line users were 9, 12, and 11 years, respectively, and the mean disease durations were 2, 6, and 4 years. Subsequent biologic users also had higher active and limited joint counts than did first-time users.

Adalimumab reduces enthesitis-related arthritis symptoms

"Enthesitis-related arthritis is a category of juvenile idiopathic arthritis that primarily affects the peripheral joints and entheses, but can also affect the sacroiliac joints and spine," said Iain Sainsbury, Ph.D., associate director for RA in global medical affairs at AbbVie, in a presentation of data on the efficacy and safety of adalimumab in children with enthesitis-related arthritis (ERA) from the M11-328 study on behalf of the study’s authors.

Since adalimumab had been previously been shown to be an effective treatment for children aged 2-17 years with polyarticular JIA, the aim of the current study was to see if it could also be of benefit in patients with ERA.

The M11-328 study was a 12-week, multicenter, double-blind trial that enrolled 46 children aged 6-18 years. They were randomized 2:1 to receive adalimumab or placebo, with continued open-label treatment for up to 3 years.

The primary endpoint, the percent change in the number of active joints with arthritis from baseline to week 12, showed a clear benefit of treatment with the biologic. Indeed, adalimumab reduced the active joint count by 62.6% vs. a reduction of 11.6% with placebo (P = .039). The treatment response was maintained with continued adalimumab treatment for 1 year. Other signs and symptoms of ERA, such as pain and enthesitis, were also reduced by the active treatment.

Dr. Sainsbury said, "The safety profile in this patient population is consistent with what we see in all other patient populations," including children aged 2 years or older with polyarticular JIA.

CHERISH 2-year data show sustained tocilizumab benefits

Dr. Eileen Baildam of Alder Hey Children’s Hospital in Liverpool, England, reported 2-year follow-up data from the CHERISH phase III trial. This trial was conducted in 58 centers in 15 countries and consisted of three phases: an open-label, lead-in phase that involved 188 children who were treated with tocilizumab for 16 weeks; a double-blind phase in which 166 children were randomized to receive tocilizumab or placebo for 24 weeks; and an open-label extension involving 60 children who were treated with tocilizumab for a further 64 weeks, bringing the total duration of therapy to 104 weeks.

Data from the second phase of the trial, at 40 weeks’ follow-up have been previously reported and "showed a very significant improvement in the flare rate in those treated vs. those on placebo," Dr. Baildam said.

A total of 82% of the 188 children enrolled in the study completed 2 years’ treatment and exhibited improvements in JIA American College of Rheumatology (ACR) 50, 70, and 90 criteria. The percentage of children who were ACR70 responders at 40 weeks and at 104 weeks were 79.3% and 86.6%, respectively, and the percentage who were ACR90 responders were a respective 50% and 70.7%.

Dr. Baildam reported a continued benefit of the anti–interleukin-6 receptor therapy, with 73.5% of children showing minimal disease activity at 40 weeks and 58.5% showing minimal disease activity at 2 years. Benefit was also seen in children who had received prior biologics.

"Overall the safety profiles remained unchanged from those at week 40, there were no deaths, and no new or unexpected safety concerns," she concluded.

The Etanercept Cohort Study is supported by Pfizer; Ms. Kearsley-Fleet had no disclosures. The CHERISH trial was supported by Pfizer; Dr. Baildam has received speaker or advisory board fees from Roche and Pfizer. The adalimumab trial was supported by AbbVie; Dr. Sainsbury is an employee of AbbVie.

LIVERPOOL, ENGLAND – Biologic therapy has shown sustained benefits for the signs and symptoms of juvenile idiopathic arthritis as well as improved height over the course of up to 2 years of treatment, according to data from four studies presented at the British Society for Rheumatology annual conference.

The studies provided evidence indicating that:

• Treatment with etanercept over 2 years helped children with juvenile idiopathic arthritis (JIA) to gain height, although their overall vertical growth still lagged behind children in the general reference population.

• When etanercept was not used as a first-line biologic, it was most common to use adalimumab instead, followed by tocilizumab and infliximab.

• Adalimumab reduced the signs and symptoms of enthesitis-related arthritis (ERA) in children by week 12 of treatment and the effects were sustained at 1-year of follow up.

• The benefits of tocilizumab in reducing disease activity to a minimal level were preserved from 40 weeks to 2 years in most patients.

Etanercept and growth in JIA

"Etanercept therapy was associated with improvement in height z score over the first 2 years of therapy," and the effect was most apparent in children who were not receiving concomitant steroids, said Lianne Kearsley-Fleet, who reported data from the British Society for Paediatric and Adolescent Rheumatology (BSPAR Etanercept Cohort Study). The prospective, observational study was initiated in 2004 with the aim of recruiting all children with JIA who were starting treatment with etanercept. For comparison, a cohort of children newly starting methotrexate was also included.

The current analysis focused on the growth of children taking the biologic therapy because children with JIA are known to have restricted growth, which may be linked to inflammation and the use of corticosteroids. Of 658 children registered in the study, 191 had height data available at baseline and at 1 and 2 years’ follow-up.

Mean height and changes in height during biologic therapy over time were assessed by calculating z scores, and compared with values set by the World Health Organization for girls and boys of a similar age who did not have JIA.

The mean age of children included in the current analysis was 11 years, with a mean disease duration of 3.5 years. The majority (65%) were female, with concomitant oral steroids in 38% and methotrexate in 58%.

The mean height z score of the study population was –0.67 at baseline, –0.57 after 1 year, and –0.45 after 2 years’ etanercept therapy. "While it is still negative [compared with children of a similar sex and age], there is still significant improvement," said Ms. Kearsley-Fleet, a research assistant from the Arthritis Research UK Centre for Epidemiology at the University of Manchester, England.

"There was a lack of evidence for association between disease activity and improved growth," the researcher noted, adding that "anti-TNF inhibitors alone may be insufficient to increase growth."

Use of non–etanercept biologics

In a poster presentation at the meeting, Ms. Kearsley-Fleet and her colleagues at her institution also presented the findings from the Biologics for Children with Rheumatic Diseases Study. This ongoing, prospective, observational cohort study is looking at the use of biologics other than etanercept in the treatment of JIA.

Since the study started in 2010, and up until early April 2014, a total of 280 children with JIA had been recruited into the biologic cohort. The study also includes a parallel control cohort of 295 children being treated with methotrexate. Just under half (46%) of the children recruited into the biologic cohort started a non–etanercept biologic as their first biologic treatment, of which the majority (75%) received the medications off label. The main alternatives to etanercept being used were adalimumab in 38% of cases, followed by tocilizumab in 25% of children, and infliximab in 23%. Other drugs used as the first biologic was anakinra (13%), rituximab (less than 1%), and abatacept (less than 1%).

Adalimumab was also a popular subsequent biologic choice in 30% of cases, with 20% of patients using tocilizumab, and 25% infliximab as a subsequent biologic choice.

The research team reported that patients using a biologic for the first time were significantly younger and had shorter disease durations than did subsequent biologic users. The mean ages of first-, second-, and third-line users were 9, 12, and 11 years, respectively, and the mean disease durations were 2, 6, and 4 years. Subsequent biologic users also had higher active and limited joint counts than did first-time users.

Adalimumab reduces enthesitis-related arthritis symptoms

"Enthesitis-related arthritis is a category of juvenile idiopathic arthritis that primarily affects the peripheral joints and entheses, but can also affect the sacroiliac joints and spine," said Iain Sainsbury, Ph.D., associate director for RA in global medical affairs at AbbVie, in a presentation of data on the efficacy and safety of adalimumab in children with enthesitis-related arthritis (ERA) from the M11-328 study on behalf of the study’s authors.

Since adalimumab had been previously been shown to be an effective treatment for children aged 2-17 years with polyarticular JIA, the aim of the current study was to see if it could also be of benefit in patients with ERA.

The M11-328 study was a 12-week, multicenter, double-blind trial that enrolled 46 children aged 6-18 years. They were randomized 2:1 to receive adalimumab or placebo, with continued open-label treatment for up to 3 years.

The primary endpoint, the percent change in the number of active joints with arthritis from baseline to week 12, showed a clear benefit of treatment with the biologic. Indeed, adalimumab reduced the active joint count by 62.6% vs. a reduction of 11.6% with placebo (P = .039). The treatment response was maintained with continued adalimumab treatment for 1 year. Other signs and symptoms of ERA, such as pain and enthesitis, were also reduced by the active treatment.

Dr. Sainsbury said, "The safety profile in this patient population is consistent with what we see in all other patient populations," including children aged 2 years or older with polyarticular JIA.

CHERISH 2-year data show sustained tocilizumab benefits

Dr. Eileen Baildam of Alder Hey Children’s Hospital in Liverpool, England, reported 2-year follow-up data from the CHERISH phase III trial. This trial was conducted in 58 centers in 15 countries and consisted of three phases: an open-label, lead-in phase that involved 188 children who were treated with tocilizumab for 16 weeks; a double-blind phase in which 166 children were randomized to receive tocilizumab or placebo for 24 weeks; and an open-label extension involving 60 children who were treated with tocilizumab for a further 64 weeks, bringing the total duration of therapy to 104 weeks.

Data from the second phase of the trial, at 40 weeks’ follow-up have been previously reported and "showed a very significant improvement in the flare rate in those treated vs. those on placebo," Dr. Baildam said.

A total of 82% of the 188 children enrolled in the study completed 2 years’ treatment and exhibited improvements in JIA American College of Rheumatology (ACR) 50, 70, and 90 criteria. The percentage of children who were ACR70 responders at 40 weeks and at 104 weeks were 79.3% and 86.6%, respectively, and the percentage who were ACR90 responders were a respective 50% and 70.7%.

Dr. Baildam reported a continued benefit of the anti–interleukin-6 receptor therapy, with 73.5% of children showing minimal disease activity at 40 weeks and 58.5% showing minimal disease activity at 2 years. Benefit was also seen in children who had received prior biologics.

"Overall the safety profiles remained unchanged from those at week 40, there were no deaths, and no new or unexpected safety concerns," she concluded.

The Etanercept Cohort Study is supported by Pfizer; Ms. Kearsley-Fleet had no disclosures. The CHERISH trial was supported by Pfizer; Dr. Baildam has received speaker or advisory board fees from Roche and Pfizer. The adalimumab trial was supported by AbbVie; Dr. Sainsbury is an employee of AbbVie.

LIVERPOOL, ENGLAND – Biologic therapy has shown sustained benefits for the signs and symptoms of juvenile idiopathic arthritis as well as improved height over the course of up to 2 years of treatment, according to data from four studies presented at the British Society for Rheumatology annual conference.

The studies provided evidence indicating that:

• Treatment with etanercept over 2 years helped children with juvenile idiopathic arthritis (JIA) to gain height, although their overall vertical growth still lagged behind children in the general reference population.

• When etanercept was not used as a first-line biologic, it was most common to use adalimumab instead, followed by tocilizumab and infliximab.

• Adalimumab reduced the signs and symptoms of enthesitis-related arthritis (ERA) in children by week 12 of treatment and the effects were sustained at 1-year of follow up.

• The benefits of tocilizumab in reducing disease activity to a minimal level were preserved from 40 weeks to 2 years in most patients.

Etanercept and growth in JIA

"Etanercept therapy was associated with improvement in height z score over the first 2 years of therapy," and the effect was most apparent in children who were not receiving concomitant steroids, said Lianne Kearsley-Fleet, who reported data from the British Society for Paediatric and Adolescent Rheumatology (BSPAR Etanercept Cohort Study). The prospective, observational study was initiated in 2004 with the aim of recruiting all children with JIA who were starting treatment with etanercept. For comparison, a cohort of children newly starting methotrexate was also included.

The current analysis focused on the growth of children taking the biologic therapy because children with JIA are known to have restricted growth, which may be linked to inflammation and the use of corticosteroids. Of 658 children registered in the study, 191 had height data available at baseline and at 1 and 2 years’ follow-up.

Mean height and changes in height during biologic therapy over time were assessed by calculating z scores, and compared with values set by the World Health Organization for girls and boys of a similar age who did not have JIA.

The mean age of children included in the current analysis was 11 years, with a mean disease duration of 3.5 years. The majority (65%) were female, with concomitant oral steroids in 38% and methotrexate in 58%.

The mean height z score of the study population was –0.67 at baseline, –0.57 after 1 year, and –0.45 after 2 years’ etanercept therapy. "While it is still negative [compared with children of a similar sex and age], there is still significant improvement," said Ms. Kearsley-Fleet, a research assistant from the Arthritis Research UK Centre for Epidemiology at the University of Manchester, England.

"There was a lack of evidence for association between disease activity and improved growth," the researcher noted, adding that "anti-TNF inhibitors alone may be insufficient to increase growth."

Use of non–etanercept biologics

In a poster presentation at the meeting, Ms. Kearsley-Fleet and her colleagues at her institution also presented the findings from the Biologics for Children with Rheumatic Diseases Study. This ongoing, prospective, observational cohort study is looking at the use of biologics other than etanercept in the treatment of JIA.

Since the study started in 2010, and up until early April 2014, a total of 280 children with JIA had been recruited into the biologic cohort. The study also includes a parallel control cohort of 295 children being treated with methotrexate. Just under half (46%) of the children recruited into the biologic cohort started a non–etanercept biologic as their first biologic treatment, of which the majority (75%) received the medications off label. The main alternatives to etanercept being used were adalimumab in 38% of cases, followed by tocilizumab in 25% of children, and infliximab in 23%. Other drugs used as the first biologic was anakinra (13%), rituximab (less than 1%), and abatacept (less than 1%).

Adalimumab was also a popular subsequent biologic choice in 30% of cases, with 20% of patients using tocilizumab, and 25% infliximab as a subsequent biologic choice.

The research team reported that patients using a biologic for the first time were significantly younger and had shorter disease durations than did subsequent biologic users. The mean ages of first-, second-, and third-line users were 9, 12, and 11 years, respectively, and the mean disease durations were 2, 6, and 4 years. Subsequent biologic users also had higher active and limited joint counts than did first-time users.

Adalimumab reduces enthesitis-related arthritis symptoms

"Enthesitis-related arthritis is a category of juvenile idiopathic arthritis that primarily affects the peripheral joints and entheses, but can also affect the sacroiliac joints and spine," said Iain Sainsbury, Ph.D., associate director for RA in global medical affairs at AbbVie, in a presentation of data on the efficacy and safety of adalimumab in children with enthesitis-related arthritis (ERA) from the M11-328 study on behalf of the study’s authors.

Since adalimumab had been previously been shown to be an effective treatment for children aged 2-17 years with polyarticular JIA, the aim of the current study was to see if it could also be of benefit in patients with ERA.

The M11-328 study was a 12-week, multicenter, double-blind trial that enrolled 46 children aged 6-18 years. They were randomized 2:1 to receive adalimumab or placebo, with continued open-label treatment for up to 3 years.

The primary endpoint, the percent change in the number of active joints with arthritis from baseline to week 12, showed a clear benefit of treatment with the biologic. Indeed, adalimumab reduced the active joint count by 62.6% vs. a reduction of 11.6% with placebo (P = .039). The treatment response was maintained with continued adalimumab treatment for 1 year. Other signs and symptoms of ERA, such as pain and enthesitis, were also reduced by the active treatment.

Dr. Sainsbury said, "The safety profile in this patient population is consistent with what we see in all other patient populations," including children aged 2 years or older with polyarticular JIA.

CHERISH 2-year data show sustained tocilizumab benefits

Dr. Eileen Baildam of Alder Hey Children’s Hospital in Liverpool, England, reported 2-year follow-up data from the CHERISH phase III trial. This trial was conducted in 58 centers in 15 countries and consisted of three phases: an open-label, lead-in phase that involved 188 children who were treated with tocilizumab for 16 weeks; a double-blind phase in which 166 children were randomized to receive tocilizumab or placebo for 24 weeks; and an open-label extension involving 60 children who were treated with tocilizumab for a further 64 weeks, bringing the total duration of therapy to 104 weeks.

Data from the second phase of the trial, at 40 weeks’ follow-up have been previously reported and "showed a very significant improvement in the flare rate in those treated vs. those on placebo," Dr. Baildam said.

A total of 82% of the 188 children enrolled in the study completed 2 years’ treatment and exhibited improvements in JIA American College of Rheumatology (ACR) 50, 70, and 90 criteria. The percentage of children who were ACR70 responders at 40 weeks and at 104 weeks were 79.3% and 86.6%, respectively, and the percentage who were ACR90 responders were a respective 50% and 70.7%.

Dr. Baildam reported a continued benefit of the anti–interleukin-6 receptor therapy, with 73.5% of children showing minimal disease activity at 40 weeks and 58.5% showing minimal disease activity at 2 years. Benefit was also seen in children who had received prior biologics.

"Overall the safety profiles remained unchanged from those at week 40, there were no deaths, and no new or unexpected safety concerns," she concluded.

The Etanercept Cohort Study is supported by Pfizer; Ms. Kearsley-Fleet had no disclosures. The CHERISH trial was supported by Pfizer; Dr. Baildam has received speaker or advisory board fees from Roche and Pfizer. The adalimumab trial was supported by AbbVie; Dr. Sainsbury is an employee of AbbVie.