Guidelines Provide New Insights Into Systemic JIA Treatment

NEW YORK - Early and aggressive therapy is warranted in the management of systemic juvenile idiopathic arthritis, which accounts for 10% of arthritis cases in children and which can be devastating, according to Dr. Randy Q. Cron, who spoke about the condition at a meeting sponsored by New York University.

Dr. Cron, director of pediatric rheumatology at the University of Alabama at Birmingham, is a coauthor of the first ever 2011 ACR Recommendations for the Treatment of Juvenile Idiopathic Arthritis (JIA) that were published on April 1 (Arthritis Care Res. 2011;63:465-82) and which include guidelines for the treatment of systemic JIA. According to the publication, "the JIA category of systemic arthritis proved to be especially challenging to evaluate. Attempts to exhaustively depict the myriad possible clinical presentations of systemic arthritis were impractical." The result was that systemic JIA guidelines include two treatment algorithms, one for the active systemic features (for example, fever) and one for the active arthritis. Patients who have both concurrent active systemic features and active arthritis can be treated according to suggestions from both algorithms.

For treating the systemic features of systemic JIA, three first-line options are available: nonsteroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, and anakinra (Kineret). It should be noted that interleukin-6 inhibitors and interleukin-1 inhibitors other than anakinra were not considered when developing the recommendations, since they were not widely available commercially at the time. TNF-alpha inhibitors were not considered because of their relatively poor effectiveness for the systemic manifestations.

While NSAID monotherapy might also help some children, the recommendations say that its use is inappropriate for patients with active fever and physician global assessment of overall disease activity (MD global) score equal to 7 of 10. It should also not be used for more than 1 month in patients with active fever.

Systemic glucocorticoids were recommended as initial therapy for patients with active fever and an MD global score of 7. Systemic glucocorticoids may also be added after 2 weeks of NSAID monotherapy in patients with active fever.

Anakinra was recommended for all patients with active fever who had poor prognostic features, no matter what they were currently taking. Anakinra was also recommended for patients who have or develop fever while on systemic glucocorticoids. Anakinra is a human recombinant interleukin-1 (IL-1) inhibitor that was approved to treat adults with moderate to severe arthritis who have not had an adequate response to conservative disease-modifying anti-rheumatic drug therapy. It is not currently approved for children with JIA.

Medications such as calcineurin inhibitors, intravenous immunoglobulin, methotrexate, and thalidomide were not formally recommended but might have roles in the treatment of systemic JIA.

For the treatment of the arthritic features of systemic JIA, initiation of NSAID monotherapy (with or without glucocorticoid joint injections) was recommended for all patients, regardless of the level of disease activity or presence of poor prognostic features. It was assumed that most patients with newly diagnosed systemic arthritis would have been started with NSAIDs. The next step would be methotrexate for all patients with active arthritis who were taking NSAID monotherapy for less than 1 month. If escalation of therapy was needed, the next choices would be either addition of a TNF-alpha inhibitor or anakinra. The recommendations indicate that initiation of anakinra should take place early rather than later in the disease course. For patients with moderate or high disease activity, regardless of features of poor prognosis, it was suggested that patients be switched from anakinra to a TNF-alpha inhibitor.

The last option is abatacept, a costimulatory blocker, for those who fail to be controlled by methotrexate or 4 months of a TNF-alpha inhibitor, and who have moderate to high disease activity.

During his presentation, Dr. Cron provided his perspective on the new systemic JIA recommendations. Most pediatric rheumatologists would probably begin with systemic corticosteroids at the onset of treatment, because that is what they are most familiar with and they are effective, he said.

He was pleased with the inclusion of anakinra in the guidelines. "With these guidelines, physicians can treat children with JIA from the start with anakinra." Inclusion of anakinra in the guidelines as a first option should help tremendously in helping patients receive reimbursement from insurance companies, he noted.

Dr. Cron cited evidence showing the effectiveness of anakinra as a first-line disease-modifying therapy in 46 patients with JIA, preventing refractory arthritis in almost 90% of patients (Arthritis Rheum. 2011;63:545-55). In this series of case studies, use of anakinra reduced elevated sedimentation rates and ferritin levels, decreased the number of active joint counts, and significantly lowered the dose of concomitant steroid therapy. "Kids can get remarkably better within days or months with anakinra. It can be a wonder drug for very sick children with systemic JIA," he said.

Although it was not discussed in the Recommendations, in his talk Dr. Cron said that anakinra is "revolutionizing" the treatment of macrophage activation syndrome (MAS) in systemic JIA (Rheumatology 2011;50:417-9) Dr. Cron reported that he has used anakinra as initial therapy to treat two children with MAS, and he found dramatic reductions in ferritin levels and liver enzymes within 2 days of initiation.

Systemic JIA is a relatively rare disease, with a prevalence of about 1 in 10,000. It has multiple systemic manifestations, including a high fever (which follows a unique pattern: typically once-daily, late-afternoon spikes in 30% of patients at presentation), rash, hepatosplenomegaly, lymphadenopathy, pericarditis, pleural effusion, pulmonary vasculitis, and even CNS stroke or seizure. Stroke or seizure might be related to MAS, a widespread coagulopathy that occurs in about 50% of patients and can be fatal.

Another common finding is asymmetry of the jaw. According to Dr. Cron, up to 80% of children with all forms of arthritis, including systemic JIA, can have arthritis of the temporomandibular joint (TMJ). This is often a subtle finding that can be overlooked until significant erosion has occurred. However, early TMJ arthritis can be detected with magnetic resonance screening.

Dr. Cron is a consultant for Genentech.

NEW YORK - Early and aggressive therapy is warranted in the management of systemic juvenile idiopathic arthritis, which accounts for 10% of arthritis cases in children and which can be devastating, according to Dr. Randy Q. Cron, who spoke about the condition at a meeting sponsored by New York University.

Dr. Cron, director of pediatric rheumatology at the University of Alabama at Birmingham, is a coauthor of the first ever 2011 ACR Recommendations for the Treatment of Juvenile Idiopathic Arthritis (JIA) that were published on April 1 (Arthritis Care Res. 2011;63:465-82) and which include guidelines for the treatment of systemic JIA. According to the publication, "the JIA category of systemic arthritis proved to be especially challenging to evaluate. Attempts to exhaustively depict the myriad possible clinical presentations of systemic arthritis were impractical." The result was that systemic JIA guidelines include two treatment algorithms, one for the active systemic features (for example, fever) and one for the active arthritis. Patients who have both concurrent active systemic features and active arthritis can be treated according to suggestions from both algorithms.

For treating the systemic features of systemic JIA, three first-line options are available: nonsteroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, and anakinra (Kineret). It should be noted that interleukin-6 inhibitors and interleukin-1 inhibitors other than anakinra were not considered when developing the recommendations, since they were not widely available commercially at the time. TNF-alpha inhibitors were not considered because of their relatively poor effectiveness for the systemic manifestations.

While NSAID monotherapy might also help some children, the recommendations say that its use is inappropriate for patients with active fever and physician global assessment of overall disease activity (MD global) score equal to 7 of 10. It should also not be used for more than 1 month in patients with active fever.

Systemic glucocorticoids were recommended as initial therapy for patients with active fever and an MD global score of 7. Systemic glucocorticoids may also be added after 2 weeks of NSAID monotherapy in patients with active fever.

Anakinra was recommended for all patients with active fever who had poor prognostic features, no matter what they were currently taking. Anakinra was also recommended for patients who have or develop fever while on systemic glucocorticoids. Anakinra is a human recombinant interleukin-1 (IL-1) inhibitor that was approved to treat adults with moderate to severe arthritis who have not had an adequate response to conservative disease-modifying anti-rheumatic drug therapy. It is not currently approved for children with JIA.

Medications such as calcineurin inhibitors, intravenous immunoglobulin, methotrexate, and thalidomide were not formally recommended but might have roles in the treatment of systemic JIA.

For the treatment of the arthritic features of systemic JIA, initiation of NSAID monotherapy (with or without glucocorticoid joint injections) was recommended for all patients, regardless of the level of disease activity or presence of poor prognostic features. It was assumed that most patients with newly diagnosed systemic arthritis would have been started with NSAIDs. The next step would be methotrexate for all patients with active arthritis who were taking NSAID monotherapy for less than 1 month. If escalation of therapy was needed, the next choices would be either addition of a TNF-alpha inhibitor or anakinra. The recommendations indicate that initiation of anakinra should take place early rather than later in the disease course. For patients with moderate or high disease activity, regardless of features of poor prognosis, it was suggested that patients be switched from anakinra to a TNF-alpha inhibitor.

The last option is abatacept, a costimulatory blocker, for those who fail to be controlled by methotrexate or 4 months of a TNF-alpha inhibitor, and who have moderate to high disease activity.

During his presentation, Dr. Cron provided his perspective on the new systemic JIA recommendations. Most pediatric rheumatologists would probably begin with systemic corticosteroids at the onset of treatment, because that is what they are most familiar with and they are effective, he said.

He was pleased with the inclusion of anakinra in the guidelines. "With these guidelines, physicians can treat children with JIA from the start with anakinra." Inclusion of anakinra in the guidelines as a first option should help tremendously in helping patients receive reimbursement from insurance companies, he noted.

Dr. Cron cited evidence showing the effectiveness of anakinra as a first-line disease-modifying therapy in 46 patients with JIA, preventing refractory arthritis in almost 90% of patients (Arthritis Rheum. 2011;63:545-55). In this series of case studies, use of anakinra reduced elevated sedimentation rates and ferritin levels, decreased the number of active joint counts, and significantly lowered the dose of concomitant steroid therapy. "Kids can get remarkably better within days or months with anakinra. It can be a wonder drug for very sick children with systemic JIA," he said.

Although it was not discussed in the Recommendations, in his talk Dr. Cron said that anakinra is "revolutionizing" the treatment of macrophage activation syndrome (MAS) in systemic JIA (Rheumatology 2011;50:417-9) Dr. Cron reported that he has used anakinra as initial therapy to treat two children with MAS, and he found dramatic reductions in ferritin levels and liver enzymes within 2 days of initiation.

Systemic JIA is a relatively rare disease, with a prevalence of about 1 in 10,000. It has multiple systemic manifestations, including a high fever (which follows a unique pattern: typically once-daily, late-afternoon spikes in 30% of patients at presentation), rash, hepatosplenomegaly, lymphadenopathy, pericarditis, pleural effusion, pulmonary vasculitis, and even CNS stroke or seizure. Stroke or seizure might be related to MAS, a widespread coagulopathy that occurs in about 50% of patients and can be fatal.

Another common finding is asymmetry of the jaw. According to Dr. Cron, up to 80% of children with all forms of arthritis, including systemic JIA, can have arthritis of the temporomandibular joint (TMJ). This is often a subtle finding that can be overlooked until significant erosion has occurred. However, early TMJ arthritis can be detected with magnetic resonance screening.

Dr. Cron is a consultant for Genentech.

NEW YORK - Early and aggressive therapy is warranted in the management of systemic juvenile idiopathic arthritis, which accounts for 10% of arthritis cases in children and which can be devastating, according to Dr. Randy Q. Cron, who spoke about the condition at a meeting sponsored by New York University.

Dr. Cron, director of pediatric rheumatology at the University of Alabama at Birmingham, is a coauthor of the first ever 2011 ACR Recommendations for the Treatment of Juvenile Idiopathic Arthritis (JIA) that were published on April 1 (Arthritis Care Res. 2011;63:465-82) and which include guidelines for the treatment of systemic JIA. According to the publication, "the JIA category of systemic arthritis proved to be especially challenging to evaluate. Attempts to exhaustively depict the myriad possible clinical presentations of systemic arthritis were impractical." The result was that systemic JIA guidelines include two treatment algorithms, one for the active systemic features (for example, fever) and one for the active arthritis. Patients who have both concurrent active systemic features and active arthritis can be treated according to suggestions from both algorithms.

For treating the systemic features of systemic JIA, three first-line options are available: nonsteroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, and anakinra (Kineret). It should be noted that interleukin-6 inhibitors and interleukin-1 inhibitors other than anakinra were not considered when developing the recommendations, since they were not widely available commercially at the time. TNF-alpha inhibitors were not considered because of their relatively poor effectiveness for the systemic manifestations.

While NSAID monotherapy might also help some children, the recommendations say that its use is inappropriate for patients with active fever and physician global assessment of overall disease activity (MD global) score equal to 7 of 10. It should also not be used for more than 1 month in patients with active fever.

Systemic glucocorticoids were recommended as initial therapy for patients with active fever and an MD global score of 7. Systemic glucocorticoids may also be added after 2 weeks of NSAID monotherapy in patients with active fever.

Anakinra was recommended for all patients with active fever who had poor prognostic features, no matter what they were currently taking. Anakinra was also recommended for patients who have or develop fever while on systemic glucocorticoids. Anakinra is a human recombinant interleukin-1 (IL-1) inhibitor that was approved to treat adults with moderate to severe arthritis who have not had an adequate response to conservative disease-modifying anti-rheumatic drug therapy. It is not currently approved for children with JIA.

Medications such as calcineurin inhibitors, intravenous immunoglobulin, methotrexate, and thalidomide were not formally recommended but might have roles in the treatment of systemic JIA.

For the treatment of the arthritic features of systemic JIA, initiation of NSAID monotherapy (with or without glucocorticoid joint injections) was recommended for all patients, regardless of the level of disease activity or presence of poor prognostic features. It was assumed that most patients with newly diagnosed systemic arthritis would have been started with NSAIDs. The next step would be methotrexate for all patients with active arthritis who were taking NSAID monotherapy for less than 1 month. If escalation of therapy was needed, the next choices would be either addition of a TNF-alpha inhibitor or anakinra. The recommendations indicate that initiation of anakinra should take place early rather than later in the disease course. For patients with moderate or high disease activity, regardless of features of poor prognosis, it was suggested that patients be switched from anakinra to a TNF-alpha inhibitor.

The last option is abatacept, a costimulatory blocker, for those who fail to be controlled by methotrexate or 4 months of a TNF-alpha inhibitor, and who have moderate to high disease activity.

During his presentation, Dr. Cron provided his perspective on the new systemic JIA recommendations. Most pediatric rheumatologists would probably begin with systemic corticosteroids at the onset of treatment, because that is what they are most familiar with and they are effective, he said.

He was pleased with the inclusion of anakinra in the guidelines. "With these guidelines, physicians can treat children with JIA from the start with anakinra." Inclusion of anakinra in the guidelines as a first option should help tremendously in helping patients receive reimbursement from insurance companies, he noted.

Dr. Cron cited evidence showing the effectiveness of anakinra as a first-line disease-modifying therapy in 46 patients with JIA, preventing refractory arthritis in almost 90% of patients (Arthritis Rheum. 2011;63:545-55). In this series of case studies, use of anakinra reduced elevated sedimentation rates and ferritin levels, decreased the number of active joint counts, and significantly lowered the dose of concomitant steroid therapy. "Kids can get remarkably better within days or months with anakinra. It can be a wonder drug for very sick children with systemic JIA," he said.

Although it was not discussed in the Recommendations, in his talk Dr. Cron said that anakinra is "revolutionizing" the treatment of macrophage activation syndrome (MAS) in systemic JIA (Rheumatology 2011;50:417-9) Dr. Cron reported that he has used anakinra as initial therapy to treat two children with MAS, and he found dramatic reductions in ferritin levels and liver enzymes within 2 days of initiation.

Systemic JIA is a relatively rare disease, with a prevalence of about 1 in 10,000. It has multiple systemic manifestations, including a high fever (which follows a unique pattern: typically once-daily, late-afternoon spikes in 30% of patients at presentation), rash, hepatosplenomegaly, lymphadenopathy, pericarditis, pleural effusion, pulmonary vasculitis, and even CNS stroke or seizure. Stroke or seizure might be related to MAS, a widespread coagulopathy that occurs in about 50% of patients and can be fatal.

Another common finding is asymmetry of the jaw. According to Dr. Cron, up to 80% of children with all forms of arthritis, including systemic JIA, can have arthritis of the temporomandibular joint (TMJ). This is often a subtle finding that can be overlooked until significant erosion has occurred. However, early TMJ arthritis can be detected with magnetic resonance screening.

Dr. Cron is a consultant for Genentech.