Revised EULAR RA guidelines keep synthetic DMARDs first

MADRID – In newly updated recommendations for managing rheumatoid arthritis, a EULAR task force retained much from its prior 2010 version but included some significant changes such as elevating the biologic drugs tocilizumab and abatacept to the same status as tumor necrosis factor inhibitors.

The 2013 draft revision may be most notable for what stayed the same from 2010, such as keeping conventional synthetic disease-modifying antirheumatic drugs (DMARDs) as the only first-line interventions for newly diagnosed patients with rheumatoid arthritis (RA). This means the update keeps all biologic DMARDs as secondary treatments reserved for patients who fail to respond adequately to or are intolerant of methotrexate or the other conventional, synthetic DMARDs cited as first-line options: sulfasalazine, hydrochloroquine, and leflunomide.

By maintaining synthetic DMARDs – either methotrexate monotherapy or in combined regimens – as its only first-line options for treating RA, the European League Against Rheumatism (EULAR) Task Force appointed to develop the new revision broke with the 2012 RA management recommendations of the American College of Rheumatology (ACR), which cited treatment with a tumor necrosis factor (TNF) inhibitor as a first-line option, with or without combination with methotrexate, for patients with early RA, high disease activity, and poor prognostic features (Arthritis Care Res. 2012;64:625-39).

The reason to keep all biologic DMARDs as second-line drugs was the evidence that supports the "efficacy of a treat-to-target strategy when adding biologics after insufficient response to methotrexate," said Dr. Josef S. Smolen, professor of rheumatology at the Medical University of Vienna, who presented the draft update during a session at the annual European Congress of Rheumatology. Dr. Smolen stressed that although the EULAR-appointed, 33-member update task force had completed all their votes to approve the draft recommendations, the update was still subject to further review and change before its eventual publication.

The new draft "does not advocate use of biologics as first DMARD strategies because the treat-to-target approach will lead to a similar overall outcome while avoiding the overtreatment of 20%-50% of patients with early RA," Dr. Smolen explained. The revision also does not endorse monotherapy with a TNF inhibitor or any other type of biologic DMARD.

Another major break from the past in the new revision is its leveling of the role for tocilizumab (Actemra) and abatacept (Orencia) alongside the several TNF inhibitor DMARDs now on the worldwide market. Last year’s ACR recommendations specified anti-TNF drugs as an option for initial therapy of patients with high disease activity and poor prognostic features, as well as low disease activity patients who get inadequate benefit from synthetic DMARDs. In the ACR recommendations, abatacept as well as rituximab (Rituxan) fell lower in the management algorithm, while tocilizumab was completely off the page.

Not only do the new EULAR recommendations place tocilizumab and abatacept on the same level as the TNF inhibitors, the EULAR draft further singles out tocilizumab as the "preferred agent" for patients who must receive a biologic DMARD as monotherapy rather than the preferred way, in combination with methotrexate. "Preference is given to combining all biologicals with methotrexate," Dr. Smolen said. The revision also cites rituximab as another biologic DMARD to consider, but it’s not ranked as high as the others.

In another change from 2010, the task force specially noted the potential benefit from using multiple conventional synthetic DMARDs for initial treatment. "The 2013 task force reiterates the evidence-based view that conventional synthetic DMARD monotherpy is effective, but based on some newer trial data on conventional synthetic DMARD combination therapy, the task force more explicitly endorses combination of conventional synthetic DMARDs early on. Preference to combination is not given because of possible limitations in the design of these trials and conflicting trial data."

The 2013 recommendations also specify a role for tofacitinib (Xeljanz), which received U.S. marketing approval late last year. Dr. Smolen highlighted that the task force reached a consensus on how to fit tofacitinib into the treatment algorithm in early April, before the European Medicines Agency denied the drug European marketing approval in late April. Despite the drug being turned down as a treatment option for European patients, "the task force was convinced of the clinical, functional, and structural efficacy of tofacitinib based on available evidence." However, citing a possibly higher risk for flare of herpes zoster, compared with biologic DMARDs, the task force said that tofacitinib should be used only in patients who had failed at least one biologic drug and "preferably two" until more experience and registry data became available.

Dr. Smolen said he has been a consultant to, a speaker for, or has received grant support from 14 pharmaceutical companies. He also said he served as the principal investigator for seven trials that assessed six different biologic agents for the treatment of rheumatoid arthritis.

Summary of EULAR’s 2013 RA management recommendations

The draft 2013 EULAR rheumatoid arthritis management recommendations includes three overarching principles and 14 recommendations. Here is a summary of the draft recommendations:

1. Therapy with DMARDs should start as soon as rheumatoid arthritis is diagnosed.

2. Treatment should aim to achieve remission or low disease activity.

3. Monitoring should be frequent, and if there is no improvement after a maximum of 3 months or if the target has not been reached by a maximum of 6 months, treatment should be adjusted.

4. Methotrexate should be part of the first treatment strategy.

5. When methotrexate is contraindicated or not tolerated, consider sulfasalazine or leflunomide as part of the treatment regimen.

6. Early treatment with a combination of conventional synthetic DMARDs is a reasonable alternative to initial methotrexate monotherapy.

7. Consider adding a low-dose glucocorticoid as part of initial treatment for up to 6 months; taper down as rapidly as clinically feasible.

8. If the treatment target is not reached, consider changing to another synthetic DMARD regimen; if the patient has poor prognostic features, consider adding a biological DMARD.

9. If a patient does not respond adequately to treatment with conventional, synthetic DMARDs – with or without concurrent treatment with a glucocorticoid – a biological DMARD should be started along with methotrexate. The biological DMARD could be a TNF inhibitor, abatacept, or tocilizumab.

10. Patients who fail to adequately respond to a biological DMARD should be switched to another biological DMARD. Patients who fail a first TNF inhibitor may be switched to a different TNF inhibitor.

11. Treatment with tofacitinib can be considered after patients fail treatment with biological DMARDs.

12. For patients in persistent remission, first taper down the corticosteroid dosage. If remission persists consider tapering down treatment with any biological DMARD, especially if the patient is also receiving one or more synthetic DMARDs.

13. In patients with sustained, long-term remission, consider tapering down the dosage of conventional, synthetic DMARDs as a shared decision between the patient and physician.

14. When adjusting therapy, take into account progression of structural damage, comorbidities, and safety issues, as well as disease activity.

Source: Dr. Smolen

[email protected]

On Twitter @mitchelzoler

MADRID – In newly updated recommendations for managing rheumatoid arthritis, a EULAR task force retained much from its prior 2010 version but included some significant changes such as elevating the biologic drugs tocilizumab and abatacept to the same status as tumor necrosis factor inhibitors.

The 2013 draft revision may be most notable for what stayed the same from 2010, such as keeping conventional synthetic disease-modifying antirheumatic drugs (DMARDs) as the only first-line interventions for newly diagnosed patients with rheumatoid arthritis (RA). This means the update keeps all biologic DMARDs as secondary treatments reserved for patients who fail to respond adequately to or are intolerant of methotrexate or the other conventional, synthetic DMARDs cited as first-line options: sulfasalazine, hydrochloroquine, and leflunomide.

By maintaining synthetic DMARDs – either methotrexate monotherapy or in combined regimens – as its only first-line options for treating RA, the European League Against Rheumatism (EULAR) Task Force appointed to develop the new revision broke with the 2012 RA management recommendations of the American College of Rheumatology (ACR), which cited treatment with a tumor necrosis factor (TNF) inhibitor as a first-line option, with or without combination with methotrexate, for patients with early RA, high disease activity, and poor prognostic features (Arthritis Care Res. 2012;64:625-39).

The reason to keep all biologic DMARDs as second-line drugs was the evidence that supports the "efficacy of a treat-to-target strategy when adding biologics after insufficient response to methotrexate," said Dr. Josef S. Smolen, professor of rheumatology at the Medical University of Vienna, who presented the draft update during a session at the annual European Congress of Rheumatology. Dr. Smolen stressed that although the EULAR-appointed, 33-member update task force had completed all their votes to approve the draft recommendations, the update was still subject to further review and change before its eventual publication.

The new draft "does not advocate use of biologics as first DMARD strategies because the treat-to-target approach will lead to a similar overall outcome while avoiding the overtreatment of 20%-50% of patients with early RA," Dr. Smolen explained. The revision also does not endorse monotherapy with a TNF inhibitor or any other type of biologic DMARD.

Another major break from the past in the new revision is its leveling of the role for tocilizumab (Actemra) and abatacept (Orencia) alongside the several TNF inhibitor DMARDs now on the worldwide market. Last year’s ACR recommendations specified anti-TNF drugs as an option for initial therapy of patients with high disease activity and poor prognostic features, as well as low disease activity patients who get inadequate benefit from synthetic DMARDs. In the ACR recommendations, abatacept as well as rituximab (Rituxan) fell lower in the management algorithm, while tocilizumab was completely off the page.

Not only do the new EULAR recommendations place tocilizumab and abatacept on the same level as the TNF inhibitors, the EULAR draft further singles out tocilizumab as the "preferred agent" for patients who must receive a biologic DMARD as monotherapy rather than the preferred way, in combination with methotrexate. "Preference is given to combining all biologicals with methotrexate," Dr. Smolen said. The revision also cites rituximab as another biologic DMARD to consider, but it’s not ranked as high as the others.

In another change from 2010, the task force specially noted the potential benefit from using multiple conventional synthetic DMARDs for initial treatment. "The 2013 task force reiterates the evidence-based view that conventional synthetic DMARD monotherpy is effective, but based on some newer trial data on conventional synthetic DMARD combination therapy, the task force more explicitly endorses combination of conventional synthetic DMARDs early on. Preference to combination is not given because of possible limitations in the design of these trials and conflicting trial data."

The 2013 recommendations also specify a role for tofacitinib (Xeljanz), which received U.S. marketing approval late last year. Dr. Smolen highlighted that the task force reached a consensus on how to fit tofacitinib into the treatment algorithm in early April, before the European Medicines Agency denied the drug European marketing approval in late April. Despite the drug being turned down as a treatment option for European patients, "the task force was convinced of the clinical, functional, and structural efficacy of tofacitinib based on available evidence." However, citing a possibly higher risk for flare of herpes zoster, compared with biologic DMARDs, the task force said that tofacitinib should be used only in patients who had failed at least one biologic drug and "preferably two" until more experience and registry data became available.

Dr. Smolen said he has been a consultant to, a speaker for, or has received grant support from 14 pharmaceutical companies. He also said he served as the principal investigator for seven trials that assessed six different biologic agents for the treatment of rheumatoid arthritis.

Summary of EULAR’s 2013 RA management recommendations

The draft 2013 EULAR rheumatoid arthritis management recommendations includes three overarching principles and 14 recommendations. Here is a summary of the draft recommendations:

1. Therapy with DMARDs should start as soon as rheumatoid arthritis is diagnosed.

2. Treatment should aim to achieve remission or low disease activity.

3. Monitoring should be frequent, and if there is no improvement after a maximum of 3 months or if the target has not been reached by a maximum of 6 months, treatment should be adjusted.

4. Methotrexate should be part of the first treatment strategy.

5. When methotrexate is contraindicated or not tolerated, consider sulfasalazine or leflunomide as part of the treatment regimen.

6. Early treatment with a combination of conventional synthetic DMARDs is a reasonable alternative to initial methotrexate monotherapy.

7. Consider adding a low-dose glucocorticoid as part of initial treatment for up to 6 months; taper down as rapidly as clinically feasible.

8. If the treatment target is not reached, consider changing to another synthetic DMARD regimen; if the patient has poor prognostic features, consider adding a biological DMARD.

9. If a patient does not respond adequately to treatment with conventional, synthetic DMARDs – with or without concurrent treatment with a glucocorticoid – a biological DMARD should be started along with methotrexate. The biological DMARD could be a TNF inhibitor, abatacept, or tocilizumab.

10. Patients who fail to adequately respond to a biological DMARD should be switched to another biological DMARD. Patients who fail a first TNF inhibitor may be switched to a different TNF inhibitor.

11. Treatment with tofacitinib can be considered after patients fail treatment with biological DMARDs.

12. For patients in persistent remission, first taper down the corticosteroid dosage. If remission persists consider tapering down treatment with any biological DMARD, especially if the patient is also receiving one or more synthetic DMARDs.

13. In patients with sustained, long-term remission, consider tapering down the dosage of conventional, synthetic DMARDs as a shared decision between the patient and physician.

14. When adjusting therapy, take into account progression of structural damage, comorbidities, and safety issues, as well as disease activity.

Source: Dr. Smolen

[email protected]

On Twitter @mitchelzoler

MADRID – In newly updated recommendations for managing rheumatoid arthritis, a EULAR task force retained much from its prior 2010 version but included some significant changes such as elevating the biologic drugs tocilizumab and abatacept to the same status as tumor necrosis factor inhibitors.

The 2013 draft revision may be most notable for what stayed the same from 2010, such as keeping conventional synthetic disease-modifying antirheumatic drugs (DMARDs) as the only first-line interventions for newly diagnosed patients with rheumatoid arthritis (RA). This means the update keeps all biologic DMARDs as secondary treatments reserved for patients who fail to respond adequately to or are intolerant of methotrexate or the other conventional, synthetic DMARDs cited as first-line options: sulfasalazine, hydrochloroquine, and leflunomide.

By maintaining synthetic DMARDs – either methotrexate monotherapy or in combined regimens – as its only first-line options for treating RA, the European League Against Rheumatism (EULAR) Task Force appointed to develop the new revision broke with the 2012 RA management recommendations of the American College of Rheumatology (ACR), which cited treatment with a tumor necrosis factor (TNF) inhibitor as a first-line option, with or without combination with methotrexate, for patients with early RA, high disease activity, and poor prognostic features (Arthritis Care Res. 2012;64:625-39).

The reason to keep all biologic DMARDs as second-line drugs was the evidence that supports the "efficacy of a treat-to-target strategy when adding biologics after insufficient response to methotrexate," said Dr. Josef S. Smolen, professor of rheumatology at the Medical University of Vienna, who presented the draft update during a session at the annual European Congress of Rheumatology. Dr. Smolen stressed that although the EULAR-appointed, 33-member update task force had completed all their votes to approve the draft recommendations, the update was still subject to further review and change before its eventual publication.

The new draft "does not advocate use of biologics as first DMARD strategies because the treat-to-target approach will lead to a similar overall outcome while avoiding the overtreatment of 20%-50% of patients with early RA," Dr. Smolen explained. The revision also does not endorse monotherapy with a TNF inhibitor or any other type of biologic DMARD.

Another major break from the past in the new revision is its leveling of the role for tocilizumab (Actemra) and abatacept (Orencia) alongside the several TNF inhibitor DMARDs now on the worldwide market. Last year’s ACR recommendations specified anti-TNF drugs as an option for initial therapy of patients with high disease activity and poor prognostic features, as well as low disease activity patients who get inadequate benefit from synthetic DMARDs. In the ACR recommendations, abatacept as well as rituximab (Rituxan) fell lower in the management algorithm, while tocilizumab was completely off the page.

Not only do the new EULAR recommendations place tocilizumab and abatacept on the same level as the TNF inhibitors, the EULAR draft further singles out tocilizumab as the "preferred agent" for patients who must receive a biologic DMARD as monotherapy rather than the preferred way, in combination with methotrexate. "Preference is given to combining all biologicals with methotrexate," Dr. Smolen said. The revision also cites rituximab as another biologic DMARD to consider, but it’s not ranked as high as the others.

In another change from 2010, the task force specially noted the potential benefit from using multiple conventional synthetic DMARDs for initial treatment. "The 2013 task force reiterates the evidence-based view that conventional synthetic DMARD monotherpy is effective, but based on some newer trial data on conventional synthetic DMARD combination therapy, the task force more explicitly endorses combination of conventional synthetic DMARDs early on. Preference to combination is not given because of possible limitations in the design of these trials and conflicting trial data."

The 2013 recommendations also specify a role for tofacitinib (Xeljanz), which received U.S. marketing approval late last year. Dr. Smolen highlighted that the task force reached a consensus on how to fit tofacitinib into the treatment algorithm in early April, before the European Medicines Agency denied the drug European marketing approval in late April. Despite the drug being turned down as a treatment option for European patients, "the task force was convinced of the clinical, functional, and structural efficacy of tofacitinib based on available evidence." However, citing a possibly higher risk for flare of herpes zoster, compared with biologic DMARDs, the task force said that tofacitinib should be used only in patients who had failed at least one biologic drug and "preferably two" until more experience and registry data became available.

Dr. Smolen said he has been a consultant to, a speaker for, or has received grant support from 14 pharmaceutical companies. He also said he served as the principal investigator for seven trials that assessed six different biologic agents for the treatment of rheumatoid arthritis.

Summary of EULAR’s 2013 RA management recommendations

The draft 2013 EULAR rheumatoid arthritis management recommendations includes three overarching principles and 14 recommendations. Here is a summary of the draft recommendations:

1. Therapy with DMARDs should start as soon as rheumatoid arthritis is diagnosed.

2. Treatment should aim to achieve remission or low disease activity.

3. Monitoring should be frequent, and if there is no improvement after a maximum of 3 months or if the target has not been reached by a maximum of 6 months, treatment should be adjusted.

4. Methotrexate should be part of the first treatment strategy.

5. When methotrexate is contraindicated or not tolerated, consider sulfasalazine or leflunomide as part of the treatment regimen.

6. Early treatment with a combination of conventional synthetic DMARDs is a reasonable alternative to initial methotrexate monotherapy.

7. Consider adding a low-dose glucocorticoid as part of initial treatment for up to 6 months; taper down as rapidly as clinically feasible.

8. If the treatment target is not reached, consider changing to another synthetic DMARD regimen; if the patient has poor prognostic features, consider adding a biological DMARD.

9. If a patient does not respond adequately to treatment with conventional, synthetic DMARDs – with or without concurrent treatment with a glucocorticoid – a biological DMARD should be started along with methotrexate. The biological DMARD could be a TNF inhibitor, abatacept, or tocilizumab.

10. Patients who fail to adequately respond to a biological DMARD should be switched to another biological DMARD. Patients who fail a first TNF inhibitor may be switched to a different TNF inhibitor.

11. Treatment with tofacitinib can be considered after patients fail treatment with biological DMARDs.

12. For patients in persistent remission, first taper down the corticosteroid dosage. If remission persists consider tapering down treatment with any biological DMARD, especially if the patient is also receiving one or more synthetic DMARDs.

13. In patients with sustained, long-term remission, consider tapering down the dosage of conventional, synthetic DMARDs as a shared decision between the patient and physician.

14. When adjusting therapy, take into account progression of structural damage, comorbidities, and safety issues, as well as disease activity.

Source: Dr. Smolen

[email protected]

On Twitter @mitchelzoler