Gains Seen in Ankylosing Spondylitis; Dx Lags

CHICAGO — Early treatment of ankylosing spondylitis may or may not prevent structural damage but it certainly improves quality of life and the ability to function, Dr. John Davis told a symposium of the American College of Rheumatology.

Dr. Davis pointed to four reasons for why ankylosing spondylitis (AS) is typically diagnosed about 8 years after disease onset: low awareness of the spondyloarthritis among nonrheumatologists; the erroneous belief among rheumatologists that AS is a “man's disease”; the difficulty in differentiating between mechanical and inflammatory back pain; and reliance on radiologic sacroiliitis, which is a late feature of AS.

Dr. Davis, who directs the Clinical Trials Center at the University of California, San Francisco, noted that the Spondylitis Association of America guidelines call for a thorough physical exam including x-rays, individual medical history, and any family history of AS, as well as blood work that includes a test for HLA-B27 antigen. Important signs of AS include pain that has persisted longer than 3 months, back pain, and stiffness that worsen with immobility but ease with physical activity, and a positive response to NSAIDs.

Research efforts are now focusing on three TNF inhibitors. Phase III trials of three biologics showed good responses that were maintained at over 2 years (etanercept and infliximab) and 24 weeks (adalimumab). All three drugs significantly outperformed placebo in phase III studies using the Assessment in AS (ASAS) International Working Group criteria and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The BASDAI form contains six visual analog scales (“none” to “very severe”) on fatigue, neck, back or hip pain, joint pain and swelling, tender areas, and morning stiffness. “If you use the BASDAI as an outcome measure you should expect about a 50% improvement in the BASDAI 50 in all the anti-TNF studies,” Dr. Davis explained, adding that physicians can print out the one-page form and have patients fill it out in their offices. The form is available at www.spondylitis.org/physician_resources/cme/basdai.pdf

In studies using the ASAS 5/6 Improvement Criteria, patient responses to tumor necrosis factor (TNF) inhibition approached 50%. Under this protocol, said Dr. Davis, patients had to have an improvement of at least 20% in four of five domains, including patient global, pain, function, inflammation, C-reactive protein, and/or spinal mobility. “Also, total spinal fusion is not a contraindication for using anti-TNF agents, as about 10% of patients who enrolled in the adalimumab study could have had total spinal fusion yet they responded to that drug,” he said, stressing that because anti-TNF therapy is lifelong, patients need to understand its risks and benefits.

International guidelines for treating patients with AS have been modified by the Spondyloarthritis Research and Treatment Network (SPARTAN) and are now in print (J. Rheumatol. 2006;33:978–82). “You can use the modified New York criteria or other evidence of spondyloarthropathy including inflammatory back pain, elevated acute phase reactants, rapid radiographic progression, spinal inflammation on imaging—including MRI—or, interestingly, ultrasound,” Dr. Davis explained, noting that French researchers found ultrasound to be especially useful in assessing enthesopathies.

“Your patient should have a BASDAI score of at least 4, and you as a physician should assign a moderate disease activity score on either a visual analog scale or the Likert scale. In general, there are three clinical presentations you need to keep in mind … the axial, peripheral arthritis excluding the hip, and the entheses. Pick out the predominant feature that you're going to treat and follow. All the manifestations should be treated with at least two courses of an NSAID, and those with significant arthritis or refractory enthesopathies should have failed either methotrexate or sulfasalazine at maximally tolerated doses for at least 3 months. For those with axial involvement, there's no requirement for nonbiologic disease-modifying antirheumatic drugs (DMARDs) and they should go directly to a biologic agent,” Dr. Davis said, adding that methotrexate and leflunomide have shown little evidence of efficacy in AS, while sulfasalizine has been shown to have effects mostly on peripheral manifestations. “Thalidomide and pamidronate interestingly have weak anti-TNF activity and have shown some clinical efficacy in small trials.”

Muscle relaxants can help, particularly when the patient is starting physical therapy. Corticosteroids injected into the sacroiliac joints alleviate refractory pain and topical corticosteroids are effective in treating acute anterior uveitis, Dr. Davis said.

After placing a patient on TNF blockade, expect a response (based on clinical trials and clinical experience) within 12 weeks. “And you want a change in your BASDAI score of at least 50% or two units, and a change in your physician global score of at least one.” Etanercept and infliximab have FDA approval, while approval of adalimumab is pending. Patients taking these medications should be screened for tuberculosis and consideration should be given to testing for hepatitis, especially in those from endemic areas, Dr. Davis said.

CHICAGO — Early treatment of ankylosing spondylitis may or may not prevent structural damage but it certainly improves quality of life and the ability to function, Dr. John Davis told a symposium of the American College of Rheumatology.

Dr. Davis pointed to four reasons for why ankylosing spondylitis (AS) is typically diagnosed about 8 years after disease onset: low awareness of the spondyloarthritis among nonrheumatologists; the erroneous belief among rheumatologists that AS is a “man's disease”; the difficulty in differentiating between mechanical and inflammatory back pain; and reliance on radiologic sacroiliitis, which is a late feature of AS.

Dr. Davis, who directs the Clinical Trials Center at the University of California, San Francisco, noted that the Spondylitis Association of America guidelines call for a thorough physical exam including x-rays, individual medical history, and any family history of AS, as well as blood work that includes a test for HLA-B27 antigen. Important signs of AS include pain that has persisted longer than 3 months, back pain, and stiffness that worsen with immobility but ease with physical activity, and a positive response to NSAIDs.

Research efforts are now focusing on three TNF inhibitors. Phase III trials of three biologics showed good responses that were maintained at over 2 years (etanercept and infliximab) and 24 weeks (adalimumab). All three drugs significantly outperformed placebo in phase III studies using the Assessment in AS (ASAS) International Working Group criteria and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The BASDAI form contains six visual analog scales (“none” to “very severe”) on fatigue, neck, back or hip pain, joint pain and swelling, tender areas, and morning stiffness. “If you use the BASDAI as an outcome measure you should expect about a 50% improvement in the BASDAI 50 in all the anti-TNF studies,” Dr. Davis explained, adding that physicians can print out the one-page form and have patients fill it out in their offices. The form is available at www.spondylitis.org/physician_resources/cme/basdai.pdf

In studies using the ASAS 5/6 Improvement Criteria, patient responses to tumor necrosis factor (TNF) inhibition approached 50%. Under this protocol, said Dr. Davis, patients had to have an improvement of at least 20% in four of five domains, including patient global, pain, function, inflammation, C-reactive protein, and/or spinal mobility. “Also, total spinal fusion is not a contraindication for using anti-TNF agents, as about 10% of patients who enrolled in the adalimumab study could have had total spinal fusion yet they responded to that drug,” he said, stressing that because anti-TNF therapy is lifelong, patients need to understand its risks and benefits.

International guidelines for treating patients with AS have been modified by the Spondyloarthritis Research and Treatment Network (SPARTAN) and are now in print (J. Rheumatol. 2006;33:978–82). “You can use the modified New York criteria or other evidence of spondyloarthropathy including inflammatory back pain, elevated acute phase reactants, rapid radiographic progression, spinal inflammation on imaging—including MRI—or, interestingly, ultrasound,” Dr. Davis explained, noting that French researchers found ultrasound to be especially useful in assessing enthesopathies.

“Your patient should have a BASDAI score of at least 4, and you as a physician should assign a moderate disease activity score on either a visual analog scale or the Likert scale. In general, there are three clinical presentations you need to keep in mind … the axial, peripheral arthritis excluding the hip, and the entheses. Pick out the predominant feature that you're going to treat and follow. All the manifestations should be treated with at least two courses of an NSAID, and those with significant arthritis or refractory enthesopathies should have failed either methotrexate or sulfasalazine at maximally tolerated doses for at least 3 months. For those with axial involvement, there's no requirement for nonbiologic disease-modifying antirheumatic drugs (DMARDs) and they should go directly to a biologic agent,” Dr. Davis said, adding that methotrexate and leflunomide have shown little evidence of efficacy in AS, while sulfasalizine has been shown to have effects mostly on peripheral manifestations. “Thalidomide and pamidronate interestingly have weak anti-TNF activity and have shown some clinical efficacy in small trials.”

Muscle relaxants can help, particularly when the patient is starting physical therapy. Corticosteroids injected into the sacroiliac joints alleviate refractory pain and topical corticosteroids are effective in treating acute anterior uveitis, Dr. Davis said.

After placing a patient on TNF blockade, expect a response (based on clinical trials and clinical experience) within 12 weeks. “And you want a change in your BASDAI score of at least 50% or two units, and a change in your physician global score of at least one.” Etanercept and infliximab have FDA approval, while approval of adalimumab is pending. Patients taking these medications should be screened for tuberculosis and consideration should be given to testing for hepatitis, especially in those from endemic areas, Dr. Davis said.

CHICAGO — Early treatment of ankylosing spondylitis may or may not prevent structural damage but it certainly improves quality of life and the ability to function, Dr. John Davis told a symposium of the American College of Rheumatology.

Dr. Davis pointed to four reasons for why ankylosing spondylitis (AS) is typically diagnosed about 8 years after disease onset: low awareness of the spondyloarthritis among nonrheumatologists; the erroneous belief among rheumatologists that AS is a “man's disease”; the difficulty in differentiating between mechanical and inflammatory back pain; and reliance on radiologic sacroiliitis, which is a late feature of AS.

Dr. Davis, who directs the Clinical Trials Center at the University of California, San Francisco, noted that the Spondylitis Association of America guidelines call for a thorough physical exam including x-rays, individual medical history, and any family history of AS, as well as blood work that includes a test for HLA-B27 antigen. Important signs of AS include pain that has persisted longer than 3 months, back pain, and stiffness that worsen with immobility but ease with physical activity, and a positive response to NSAIDs.

Research efforts are now focusing on three TNF inhibitors. Phase III trials of three biologics showed good responses that were maintained at over 2 years (etanercept and infliximab) and 24 weeks (adalimumab). All three drugs significantly outperformed placebo in phase III studies using the Assessment in AS (ASAS) International Working Group criteria and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The BASDAI form contains six visual analog scales (“none” to “very severe”) on fatigue, neck, back or hip pain, joint pain and swelling, tender areas, and morning stiffness. “If you use the BASDAI as an outcome measure you should expect about a 50% improvement in the BASDAI 50 in all the anti-TNF studies,” Dr. Davis explained, adding that physicians can print out the one-page form and have patients fill it out in their offices. The form is available at www.spondylitis.org/physician_resources/cme/basdai.pdf

In studies using the ASAS 5/6 Improvement Criteria, patient responses to tumor necrosis factor (TNF) inhibition approached 50%. Under this protocol, said Dr. Davis, patients had to have an improvement of at least 20% in four of five domains, including patient global, pain, function, inflammation, C-reactive protein, and/or spinal mobility. “Also, total spinal fusion is not a contraindication for using anti-TNF agents, as about 10% of patients who enrolled in the adalimumab study could have had total spinal fusion yet they responded to that drug,” he said, stressing that because anti-TNF therapy is lifelong, patients need to understand its risks and benefits.

International guidelines for treating patients with AS have been modified by the Spondyloarthritis Research and Treatment Network (SPARTAN) and are now in print (J. Rheumatol. 2006;33:978–82). “You can use the modified New York criteria or other evidence of spondyloarthropathy including inflammatory back pain, elevated acute phase reactants, rapid radiographic progression, spinal inflammation on imaging—including MRI—or, interestingly, ultrasound,” Dr. Davis explained, noting that French researchers found ultrasound to be especially useful in assessing enthesopathies.

“Your patient should have a BASDAI score of at least 4, and you as a physician should assign a moderate disease activity score on either a visual analog scale or the Likert scale. In general, there are three clinical presentations you need to keep in mind … the axial, peripheral arthritis excluding the hip, and the entheses. Pick out the predominant feature that you're going to treat and follow. All the manifestations should be treated with at least two courses of an NSAID, and those with significant arthritis or refractory enthesopathies should have failed either methotrexate or sulfasalazine at maximally tolerated doses for at least 3 months. For those with axial involvement, there's no requirement for nonbiologic disease-modifying antirheumatic drugs (DMARDs) and they should go directly to a biologic agent,” Dr. Davis said, adding that methotrexate and leflunomide have shown little evidence of efficacy in AS, while sulfasalizine has been shown to have effects mostly on peripheral manifestations. “Thalidomide and pamidronate interestingly have weak anti-TNF activity and have shown some clinical efficacy in small trials.”

Muscle relaxants can help, particularly when the patient is starting physical therapy. Corticosteroids injected into the sacroiliac joints alleviate refractory pain and topical corticosteroids are effective in treating acute anterior uveitis, Dr. Davis said.

After placing a patient on TNF blockade, expect a response (based on clinical trials and clinical experience) within 12 weeks. “And you want a change in your BASDAI score of at least 50% or two units, and a change in your physician global score of at least one.” Etanercept and infliximab have FDA approval, while approval of adalimumab is pending. Patients taking these medications should be screened for tuberculosis and consideration should be given to testing for hepatitis, especially in those from endemic areas, Dr. Davis said.