New Ankylosing Spondylitis Guidelines Highlight TNF Inhibitors

ROME — Revised recommendations for managing ankylosing spondylitis from two international societies set tumor necrosis factor inhibitors as the cornerstone of treatment for patients who fail to have an adequate response to treatment with NSAIDs.

The new recommendations also put new emphasis on the extra-articular manifestations of ankylosing spondylitis (AS) – psoriasis, uveitis, and inflammatory bowel disease – and stress that these manifestations should be managed in collaboration with other specialists, along with recognition that AS patients also face increased risks for cardiovascular disease and osteoporosis, Dr. Jürgen Braun said at the annual European Congress of Rheumatology.

AS patients who present with psoriasis, uveitis, or inflammatory bowel disease may do better on a monoclonal antibody–based TNF inhibitor because those forms seem to work better on the extra-articular manifestations than do soluble receptor–based TNF inhibitors, Dr. Braun said in an interview. On the other hand, soluble receptor–based anti-TNF drugs appear to be somewhat safer, in that they appear to pose a reduced risk for activating either latent tuberculosis or herpes zoster infections, he said.

In the treatment of AS, the main difference “compared with rheumatoid arthritis is that conventional disease-modifying antirheumatic drugs [DMARDs] do not work for axial symptoms,” which exist in the majority of AS patients. “This makes TNF inhibitors almost first-line agents, after [NSAIDs]. All TNF inhibitors work similarly well for the spine, peripheral joints, and entheses.” For AS patients whose major problem is peripheral joint disease, a conventional DMARD – specifically sulfasalazine – can be effective, said Dr. Braun, director of the Center for Rheumatic Diseases in Herne, Germany.

The new treatment guidelines complement the new classification criteria for AS and axial spondyloarthritis that were published by the ASAS (Assessment of Spondyloarthritis International Association) last year (Ann. Rheum. Dis. 2009;68:777-83). The new classification criteria mean that rheumatologists can “treat when they see inflammation on MRI” instead of having to wait for patients to develop radiographic changes, Dr. Braun noted. The new classification criteria – coupled with the new treatment recommendations – put treatment on a faster track, and give physicians backup to put those AS patients who don’t respond within a few weeks to NSAID therapy on a TNF inhibitor relatively early in the course of their disease.

A panel of 18 rheumatologists, two orthopedic surgeons, one physiotherapist, and four patients formed by ASAS and EULAR (European League Against Rheumatism) devised the new treatment recommendations over 2 days in February in Zurich. They based their decisions on a review of the published literature since 2005.

The recommendations consist of 11 specific AS management directives that cover everything from general treatment to surgery, and rule out other causes in patients who do respond to standard care. They will appear in an article the EULAR journal, Annals of the Rheumatic Diseases, in the near future.

The recommendations are as follows:

• General: Treatment of patients with AS should be tailored to their current disease manifestations; their current level of symptoms, clinical findings, and prognostic indicators; and the patient’s general clinical status, including age, gender, co-morbidities, concomitant medications, and psychosocial status.

• Disease monitoring:Monitoring should include a patient’s history, clinical parameters, laboratory tests, and imaging. Frequency of monitoring should be individualized based on the course of symptoms, symptom severity, and treatment.

• Non-pharmacologic treatment: The cornerstones are education about AS and regular exercise.

• Extra-articular manifestations: Psoriasis, uveitis, and inflammatory bowel disease need collaborative management by specialists. Rheumatologists should also be aware of the increased risk for cardiovascular disease and osteoporosis in AS patients.

• NSAIDs: NSAIDs, including selective cyclooxygenase-2 inhibitors (COXIBs), are the recommended first-line treatment for patients with AS who have pain and stiffness. Continuous NSAID treatment is preferred for patients with persistently active, symptomatic disease. A patient’s cardiovascular and gastrointestinal risks should be considered when prescribing NSAIDs.

• Analgesics: Pain medications such as paracetamol and opioids or opioid-like drugs might be considered to treat residual pain if previously recommended treatments failed, are contraindicated, or poorly tolerated.

• Corticosteroids: Consider local corticosteroid injections at sites of musculoskeletal inflammation. Systemic corticosteroids for treating axial disease is not supported by evidence.

• DMARDS: No evidence supports the efficacy of DMARDS, including sulfasalazine, for treating axial disease. Sulfasalazine may be considered for patients with peripheral arthritis.

• Biologic therapy: A TNF inhibitor should be given to patients with persistently high disease activity despite conventional treatments according to ASAS recommendations. No evidence supports the obligatory use of DMARDs before or during treatment with a TNF inhibitor in patients with axial AS. No evidence supports a difference in the efficacy of the various TNF inhibitors on axial and articular/entheseal disease manifestations. In patients with inflammatory bowel disease, differences in the gastrointestinal efficacy of the various TNF inhibitors should be taken into account. No evidence supports the efficacy of any other biologic agent aside from TNF inhibitors in AS patients. Switching to a second TNF inhibitor may benefit AS patients, especially those who lose response to the first drug they receive.

• Surgery: Consider total hip arthroplasty in patients with refractory pain or disability and radiographic evidence of structural damage independent of age. Spinal corrective osteotomy may be considered in patients with severe disabling deformity. AS patients with an acute vertebral fracture need a consultation with a spinal surgeon.

• If a patient has a significant change in disease course, other causes of inflammation, such as a spinal fracture, should be considered and an appropriate evaluation, including imaging, should be done.

Dr. Braun has received research support from, been a consultant to, and served as a speaker for Abbott Laboratories, Amgen Inc., Bristol-Myers Squibb Co., Centocor Inc., Merck/Schering-Plough Pharmaceuticals, Merck Sharp and Dohme Corp., Novartis, Pfizer Inc./Wyeth, and Roche.

ROME — Revised recommendations for managing ankylosing spondylitis from two international societies set tumor necrosis factor inhibitors as the cornerstone of treatment for patients who fail to have an adequate response to treatment with NSAIDs.

The new recommendations also put new emphasis on the extra-articular manifestations of ankylosing spondylitis (AS) – psoriasis, uveitis, and inflammatory bowel disease – and stress that these manifestations should be managed in collaboration with other specialists, along with recognition that AS patients also face increased risks for cardiovascular disease and osteoporosis, Dr. Jürgen Braun said at the annual European Congress of Rheumatology.

AS patients who present with psoriasis, uveitis, or inflammatory bowel disease may do better on a monoclonal antibody–based TNF inhibitor because those forms seem to work better on the extra-articular manifestations than do soluble receptor–based TNF inhibitors, Dr. Braun said in an interview. On the other hand, soluble receptor–based anti-TNF drugs appear to be somewhat safer, in that they appear to pose a reduced risk for activating either latent tuberculosis or herpes zoster infections, he said.

In the treatment of AS, the main difference “compared with rheumatoid arthritis is that conventional disease-modifying antirheumatic drugs [DMARDs] do not work for axial symptoms,” which exist in the majority of AS patients. “This makes TNF inhibitors almost first-line agents, after [NSAIDs]. All TNF inhibitors work similarly well for the spine, peripheral joints, and entheses.” For AS patients whose major problem is peripheral joint disease, a conventional DMARD – specifically sulfasalazine – can be effective, said Dr. Braun, director of the Center for Rheumatic Diseases in Herne, Germany.

The new treatment guidelines complement the new classification criteria for AS and axial spondyloarthritis that were published by the ASAS (Assessment of Spondyloarthritis International Association) last year (Ann. Rheum. Dis. 2009;68:777-83). The new classification criteria mean that rheumatologists can “treat when they see inflammation on MRI” instead of having to wait for patients to develop radiographic changes, Dr. Braun noted. The new classification criteria – coupled with the new treatment recommendations – put treatment on a faster track, and give physicians backup to put those AS patients who don’t respond within a few weeks to NSAID therapy on a TNF inhibitor relatively early in the course of their disease.

A panel of 18 rheumatologists, two orthopedic surgeons, one physiotherapist, and four patients formed by ASAS and EULAR (European League Against Rheumatism) devised the new treatment recommendations over 2 days in February in Zurich. They based their decisions on a review of the published literature since 2005.

The recommendations consist of 11 specific AS management directives that cover everything from general treatment to surgery, and rule out other causes in patients who do respond to standard care. They will appear in an article the EULAR journal, Annals of the Rheumatic Diseases, in the near future.

The recommendations are as follows:

• General: Treatment of patients with AS should be tailored to their current disease manifestations; their current level of symptoms, clinical findings, and prognostic indicators; and the patient’s general clinical status, including age, gender, co-morbidities, concomitant medications, and psychosocial status.

• Disease monitoring:Monitoring should include a patient’s history, clinical parameters, laboratory tests, and imaging. Frequency of monitoring should be individualized based on the course of symptoms, symptom severity, and treatment.

• Non-pharmacologic treatment: The cornerstones are education about AS and regular exercise.

• Extra-articular manifestations: Psoriasis, uveitis, and inflammatory bowel disease need collaborative management by specialists. Rheumatologists should also be aware of the increased risk for cardiovascular disease and osteoporosis in AS patients.

• NSAIDs: NSAIDs, including selective cyclooxygenase-2 inhibitors (COXIBs), are the recommended first-line treatment for patients with AS who have pain and stiffness. Continuous NSAID treatment is preferred for patients with persistently active, symptomatic disease. A patient’s cardiovascular and gastrointestinal risks should be considered when prescribing NSAIDs.

• Analgesics: Pain medications such as paracetamol and opioids or opioid-like drugs might be considered to treat residual pain if previously recommended treatments failed, are contraindicated, or poorly tolerated.

• Corticosteroids: Consider local corticosteroid injections at sites of musculoskeletal inflammation. Systemic corticosteroids for treating axial disease is not supported by evidence.

• DMARDS: No evidence supports the efficacy of DMARDS, including sulfasalazine, for treating axial disease. Sulfasalazine may be considered for patients with peripheral arthritis.

• Biologic therapy: A TNF inhibitor should be given to patients with persistently high disease activity despite conventional treatments according to ASAS recommendations. No evidence supports the obligatory use of DMARDs before or during treatment with a TNF inhibitor in patients with axial AS. No evidence supports a difference in the efficacy of the various TNF inhibitors on axial and articular/entheseal disease manifestations. In patients with inflammatory bowel disease, differences in the gastrointestinal efficacy of the various TNF inhibitors should be taken into account. No evidence supports the efficacy of any other biologic agent aside from TNF inhibitors in AS patients. Switching to a second TNF inhibitor may benefit AS patients, especially those who lose response to the first drug they receive.

• Surgery: Consider total hip arthroplasty in patients with refractory pain or disability and radiographic evidence of structural damage independent of age. Spinal corrective osteotomy may be considered in patients with severe disabling deformity. AS patients with an acute vertebral fracture need a consultation with a spinal surgeon.

• If a patient has a significant change in disease course, other causes of inflammation, such as a spinal fracture, should be considered and an appropriate evaluation, including imaging, should be done.

Dr. Braun has received research support from, been a consultant to, and served as a speaker for Abbott Laboratories, Amgen Inc., Bristol-Myers Squibb Co., Centocor Inc., Merck/Schering-Plough Pharmaceuticals, Merck Sharp and Dohme Corp., Novartis, Pfizer Inc./Wyeth, and Roche.

ROME — Revised recommendations for managing ankylosing spondylitis from two international societies set tumor necrosis factor inhibitors as the cornerstone of treatment for patients who fail to have an adequate response to treatment with NSAIDs.

The new recommendations also put new emphasis on the extra-articular manifestations of ankylosing spondylitis (AS) – psoriasis, uveitis, and inflammatory bowel disease – and stress that these manifestations should be managed in collaboration with other specialists, along with recognition that AS patients also face increased risks for cardiovascular disease and osteoporosis, Dr. Jürgen Braun said at the annual European Congress of Rheumatology.

AS patients who present with psoriasis, uveitis, or inflammatory bowel disease may do better on a monoclonal antibody–based TNF inhibitor because those forms seem to work better on the extra-articular manifestations than do soluble receptor–based TNF inhibitors, Dr. Braun said in an interview. On the other hand, soluble receptor–based anti-TNF drugs appear to be somewhat safer, in that they appear to pose a reduced risk for activating either latent tuberculosis or herpes zoster infections, he said.

In the treatment of AS, the main difference “compared with rheumatoid arthritis is that conventional disease-modifying antirheumatic drugs [DMARDs] do not work for axial symptoms,” which exist in the majority of AS patients. “This makes TNF inhibitors almost first-line agents, after [NSAIDs]. All TNF inhibitors work similarly well for the spine, peripheral joints, and entheses.” For AS patients whose major problem is peripheral joint disease, a conventional DMARD – specifically sulfasalazine – can be effective, said Dr. Braun, director of the Center for Rheumatic Diseases in Herne, Germany.

The new treatment guidelines complement the new classification criteria for AS and axial spondyloarthritis that were published by the ASAS (Assessment of Spondyloarthritis International Association) last year (Ann. Rheum. Dis. 2009;68:777-83). The new classification criteria mean that rheumatologists can “treat when they see inflammation on MRI” instead of having to wait for patients to develop radiographic changes, Dr. Braun noted. The new classification criteria – coupled with the new treatment recommendations – put treatment on a faster track, and give physicians backup to put those AS patients who don’t respond within a few weeks to NSAID therapy on a TNF inhibitor relatively early in the course of their disease.

A panel of 18 rheumatologists, two orthopedic surgeons, one physiotherapist, and four patients formed by ASAS and EULAR (European League Against Rheumatism) devised the new treatment recommendations over 2 days in February in Zurich. They based their decisions on a review of the published literature since 2005.

The recommendations consist of 11 specific AS management directives that cover everything from general treatment to surgery, and rule out other causes in patients who do respond to standard care. They will appear in an article the EULAR journal, Annals of the Rheumatic Diseases, in the near future.

The recommendations are as follows:

• General: Treatment of patients with AS should be tailored to their current disease manifestations; their current level of symptoms, clinical findings, and prognostic indicators; and the patient’s general clinical status, including age, gender, co-morbidities, concomitant medications, and psychosocial status.

• Disease monitoring:Monitoring should include a patient’s history, clinical parameters, laboratory tests, and imaging. Frequency of monitoring should be individualized based on the course of symptoms, symptom severity, and treatment.

• Non-pharmacologic treatment: The cornerstones are education about AS and regular exercise.

• Extra-articular manifestations: Psoriasis, uveitis, and inflammatory bowel disease need collaborative management by specialists. Rheumatologists should also be aware of the increased risk for cardiovascular disease and osteoporosis in AS patients.

• NSAIDs: NSAIDs, including selective cyclooxygenase-2 inhibitors (COXIBs), are the recommended first-line treatment for patients with AS who have pain and stiffness. Continuous NSAID treatment is preferred for patients with persistently active, symptomatic disease. A patient’s cardiovascular and gastrointestinal risks should be considered when prescribing NSAIDs.

• Analgesics: Pain medications such as paracetamol and opioids or opioid-like drugs might be considered to treat residual pain if previously recommended treatments failed, are contraindicated, or poorly tolerated.

• Corticosteroids: Consider local corticosteroid injections at sites of musculoskeletal inflammation. Systemic corticosteroids for treating axial disease is not supported by evidence.

• DMARDS: No evidence supports the efficacy of DMARDS, including sulfasalazine, for treating axial disease. Sulfasalazine may be considered for patients with peripheral arthritis.

• Biologic therapy: A TNF inhibitor should be given to patients with persistently high disease activity despite conventional treatments according to ASAS recommendations. No evidence supports the obligatory use of DMARDs before or during treatment with a TNF inhibitor in patients with axial AS. No evidence supports a difference in the efficacy of the various TNF inhibitors on axial and articular/entheseal disease manifestations. In patients with inflammatory bowel disease, differences in the gastrointestinal efficacy of the various TNF inhibitors should be taken into account. No evidence supports the efficacy of any other biologic agent aside from TNF inhibitors in AS patients. Switching to a second TNF inhibitor may benefit AS patients, especially those who lose response to the first drug they receive.

• Surgery: Consider total hip arthroplasty in patients with refractory pain or disability and radiographic evidence of structural damage independent of age. Spinal corrective osteotomy may be considered in patients with severe disabling deformity. AS patients with an acute vertebral fracture need a consultation with a spinal surgeon.

• If a patient has a significant change in disease course, other causes of inflammation, such as a spinal fracture, should be considered and an appropriate evaluation, including imaging, should be done.

Dr. Braun has received research support from, been a consultant to, and served as a speaker for Abbott Laboratories, Amgen Inc., Bristol-Myers Squibb Co., Centocor Inc., Merck/Schering-Plough Pharmaceuticals, Merck Sharp and Dohme Corp., Novartis, Pfizer Inc./Wyeth, and Roche.