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Inflammation in ankylosing spondylitis was associated with new spinal bone formation in a 12-year follow-up study of 184 patients in the Outcome in AS International Study (OASIS).
"We have demonstrated here for the first time that the effect of disease activity on radiographic damage is actually rather impressive and longitudinal: Per one ASDAS unit increase a 0.7 mSASSS (modified Stoke Ankylosing Spondylitis Spine Score) units progression in 2 years can be expected. This longitudinal relationship was pertinent over the entire 12 years of follow-up," said Dr. Sofia Ramiro of the Amsterdam Rheumatology Center, University of Amsterdam.
The effect was more pronounced in men and in the earlier phases of the disease, Dr. Ramiro and her associates wrote in an article published online May 7 in Annals of the Rheumatic Diseases (doi:10.1136/annrheumdis-2014-205178).
For the study, all patients had biennial clinical and radiographic assessments and two readers independently scored the x-rays according to the mSASSS. Disease activity measures included the Bath AS Disease Activity Index (BASDAI), AS Disease Activity Index (ASDAS)-C-reactive protein (CRP), CRP, erythrocyte sedimentation rate (ESR), patient’s global assessment, and spinal pain.
As a disease activity measure, ASDAS outperformed the models with all other disease activity measures. The finding importantly adds to the validity of ASDAS as the disease activity measure of choice, the researchers said.
Patients with an ASDAS less than 1.3 at baseline had an average progression of 0.71 mSASSS units/2-years. Those with an ASDAS of more than 3.5 at baseline had a progression of 3.1 mSASSS units/2-year progression. A similar relationship was found for BASDAI: patients with a BASDAI less than 4 at baseline had an average progression of 1.4 mSASSS units/2 years, while patients with a BASDAI of 4 or more at baseline had an average progression of 2.7 mSASSS units/2 years.
However, inflammation "by far does not fully explain radiographic damage in AS: Even without measurable disease activity there is still considerable radiographic progression," they said. Patients who have inactive disease for the entire 12 years still can expect a progression of 5 mSASSS units on average. It seems as if increased bone formation in AS is partly constitutive and partly inflammation dependent.
The effect of disease activity on radiographic progression seems to be stronger in men, who had an additional progression of about 1 mSASSS unit per 2-year interval per additional unit of ASDAS. The researchers also found a stronger effect of disease activity on radiographic progression in the early phase of AS.
The models with ASDAS as the disease activity measure fitted the data better than did models with BASDAI, CRP, or BASDAI+CRP. An increase of one ASDAS unit led to an increase of 0.72 mSASSS units/2 years. An ASDAS exceeding 3.5 compared with an ASDAS of less than 1.3 resulted in an additional 2-year progression of 2.31 mSASSS units.
Dr. Romero was supported by the Fundação para a Ciência e Tecnologia (FCT) grant SFRH/BD/68684/2010.
We now have clear evidence that inflammation and new bone formation are related in ankylosing spondylitis. The current model even allows such a relationship to be quantified, with an increase of 1 ASDAS unit leading to an increase of 0.72 mSASSS units/2 years, an estimation that might also be useful for daily clinical practice.
However, the mean disease duration in this study was rather long at 20 years and can be seen as a limitation, since it is unclear whether an ASDAS increase has a similar effect on radiographic progression at an earlier stage of the disease. Thus, structural damage already present would lead to new or further bone formation over time, independent of the presence of inflammation. Further, only 30% of the study patients were women, and the limited data indicate that there is no or less correlation between parameters of activity and radiographic progression in women.
Nevertheless, the effect of elevated disease activity on new bone formation shown here is a big advance in understanding this rather complex relationship and is also potentially important for future treatment strategies, including the ‘treat to target’ approach. However, it has to be shown in therapeutic studies that lowering disease activity effectively can indeed retard radiographic progression in AS.
Long-term treatment studies in patients with early axial ankylosing spondylitis, including those with nonradiographic axial disease before structural damage is visible on x-ray, are now possible based on the new ASAS classification criteria. In light of the current evidence, we would hypothesize that early treatment with a tumor necrosis factor (TNF) blocker might retard radiographic progression, but that in long-standing ankylosing spondylitis a combination with another drug inhibiting new bone formation might be necessary. As some evidence indicates that NSAIDs might be able to inhibit radiographic progression, a clinical trial investigating the effect of combination therapy of a TNF blocker with an NSAID would be of interest.
Dr. Joachim Sieper and Dr. Denis Poddubnyy are with the Campus Benjamin Franklin, Charité, Berlin. They reported having no relevant financial disclosures. They made their remarks in an editorial that accompanied the study (Ann. Rheum Dis. 2014 May 8 [10.1136/annrheumdis-2014-205464]).
We now have clear evidence that inflammation and new bone formation are related in ankylosing spondylitis. The current model even allows such a relationship to be quantified, with an increase of 1 ASDAS unit leading to an increase of 0.72 mSASSS units/2 years, an estimation that might also be useful for daily clinical practice.
However, the mean disease duration in this study was rather long at 20 years and can be seen as a limitation, since it is unclear whether an ASDAS increase has a similar effect on radiographic progression at an earlier stage of the disease. Thus, structural damage already present would lead to new or further bone formation over time, independent of the presence of inflammation. Further, only 30% of the study patients were women, and the limited data indicate that there is no or less correlation between parameters of activity and radiographic progression in women.
Nevertheless, the effect of elevated disease activity on new bone formation shown here is a big advance in understanding this rather complex relationship and is also potentially important for future treatment strategies, including the ‘treat to target’ approach. However, it has to be shown in therapeutic studies that lowering disease activity effectively can indeed retard radiographic progression in AS.
Long-term treatment studies in patients with early axial ankylosing spondylitis, including those with nonradiographic axial disease before structural damage is visible on x-ray, are now possible based on the new ASAS classification criteria. In light of the current evidence, we would hypothesize that early treatment with a tumor necrosis factor (TNF) blocker might retard radiographic progression, but that in long-standing ankylosing spondylitis a combination with another drug inhibiting new bone formation might be necessary. As some evidence indicates that NSAIDs might be able to inhibit radiographic progression, a clinical trial investigating the effect of combination therapy of a TNF blocker with an NSAID would be of interest.
Dr. Joachim Sieper and Dr. Denis Poddubnyy are with the Campus Benjamin Franklin, Charité, Berlin. They reported having no relevant financial disclosures. They made their remarks in an editorial that accompanied the study (Ann. Rheum Dis. 2014 May 8 [10.1136/annrheumdis-2014-205464]).
We now have clear evidence that inflammation and new bone formation are related in ankylosing spondylitis. The current model even allows such a relationship to be quantified, with an increase of 1 ASDAS unit leading to an increase of 0.72 mSASSS units/2 years, an estimation that might also be useful for daily clinical practice.
However, the mean disease duration in this study was rather long at 20 years and can be seen as a limitation, since it is unclear whether an ASDAS increase has a similar effect on radiographic progression at an earlier stage of the disease. Thus, structural damage already present would lead to new or further bone formation over time, independent of the presence of inflammation. Further, only 30% of the study patients were women, and the limited data indicate that there is no or less correlation between parameters of activity and radiographic progression in women.
Nevertheless, the effect of elevated disease activity on new bone formation shown here is a big advance in understanding this rather complex relationship and is also potentially important for future treatment strategies, including the ‘treat to target’ approach. However, it has to be shown in therapeutic studies that lowering disease activity effectively can indeed retard radiographic progression in AS.
Long-term treatment studies in patients with early axial ankylosing spondylitis, including those with nonradiographic axial disease before structural damage is visible on x-ray, are now possible based on the new ASAS classification criteria. In light of the current evidence, we would hypothesize that early treatment with a tumor necrosis factor (TNF) blocker might retard radiographic progression, but that in long-standing ankylosing spondylitis a combination with another drug inhibiting new bone formation might be necessary. As some evidence indicates that NSAIDs might be able to inhibit radiographic progression, a clinical trial investigating the effect of combination therapy of a TNF blocker with an NSAID would be of interest.
Dr. Joachim Sieper and Dr. Denis Poddubnyy are with the Campus Benjamin Franklin, Charité, Berlin. They reported having no relevant financial disclosures. They made their remarks in an editorial that accompanied the study (Ann. Rheum Dis. 2014 May 8 [10.1136/annrheumdis-2014-205464]).
Inflammation in ankylosing spondylitis was associated with new spinal bone formation in a 12-year follow-up study of 184 patients in the Outcome in AS International Study (OASIS).
"We have demonstrated here for the first time that the effect of disease activity on radiographic damage is actually rather impressive and longitudinal: Per one ASDAS unit increase a 0.7 mSASSS (modified Stoke Ankylosing Spondylitis Spine Score) units progression in 2 years can be expected. This longitudinal relationship was pertinent over the entire 12 years of follow-up," said Dr. Sofia Ramiro of the Amsterdam Rheumatology Center, University of Amsterdam.
The effect was more pronounced in men and in the earlier phases of the disease, Dr. Ramiro and her associates wrote in an article published online May 7 in Annals of the Rheumatic Diseases (doi:10.1136/annrheumdis-2014-205178).
For the study, all patients had biennial clinical and radiographic assessments and two readers independently scored the x-rays according to the mSASSS. Disease activity measures included the Bath AS Disease Activity Index (BASDAI), AS Disease Activity Index (ASDAS)-C-reactive protein (CRP), CRP, erythrocyte sedimentation rate (ESR), patient’s global assessment, and spinal pain.
As a disease activity measure, ASDAS outperformed the models with all other disease activity measures. The finding importantly adds to the validity of ASDAS as the disease activity measure of choice, the researchers said.
Patients with an ASDAS less than 1.3 at baseline had an average progression of 0.71 mSASSS units/2-years. Those with an ASDAS of more than 3.5 at baseline had a progression of 3.1 mSASSS units/2-year progression. A similar relationship was found for BASDAI: patients with a BASDAI less than 4 at baseline had an average progression of 1.4 mSASSS units/2 years, while patients with a BASDAI of 4 or more at baseline had an average progression of 2.7 mSASSS units/2 years.
However, inflammation "by far does not fully explain radiographic damage in AS: Even without measurable disease activity there is still considerable radiographic progression," they said. Patients who have inactive disease for the entire 12 years still can expect a progression of 5 mSASSS units on average. It seems as if increased bone formation in AS is partly constitutive and partly inflammation dependent.
The effect of disease activity on radiographic progression seems to be stronger in men, who had an additional progression of about 1 mSASSS unit per 2-year interval per additional unit of ASDAS. The researchers also found a stronger effect of disease activity on radiographic progression in the early phase of AS.
The models with ASDAS as the disease activity measure fitted the data better than did models with BASDAI, CRP, or BASDAI+CRP. An increase of one ASDAS unit led to an increase of 0.72 mSASSS units/2 years. An ASDAS exceeding 3.5 compared with an ASDAS of less than 1.3 resulted in an additional 2-year progression of 2.31 mSASSS units.
Dr. Romero was supported by the Fundação para a Ciência e Tecnologia (FCT) grant SFRH/BD/68684/2010.
Inflammation in ankylosing spondylitis was associated with new spinal bone formation in a 12-year follow-up study of 184 patients in the Outcome in AS International Study (OASIS).
"We have demonstrated here for the first time that the effect of disease activity on radiographic damage is actually rather impressive and longitudinal: Per one ASDAS unit increase a 0.7 mSASSS (modified Stoke Ankylosing Spondylitis Spine Score) units progression in 2 years can be expected. This longitudinal relationship was pertinent over the entire 12 years of follow-up," said Dr. Sofia Ramiro of the Amsterdam Rheumatology Center, University of Amsterdam.
The effect was more pronounced in men and in the earlier phases of the disease, Dr. Ramiro and her associates wrote in an article published online May 7 in Annals of the Rheumatic Diseases (doi:10.1136/annrheumdis-2014-205178).
For the study, all patients had biennial clinical and radiographic assessments and two readers independently scored the x-rays according to the mSASSS. Disease activity measures included the Bath AS Disease Activity Index (BASDAI), AS Disease Activity Index (ASDAS)-C-reactive protein (CRP), CRP, erythrocyte sedimentation rate (ESR), patient’s global assessment, and spinal pain.
As a disease activity measure, ASDAS outperformed the models with all other disease activity measures. The finding importantly adds to the validity of ASDAS as the disease activity measure of choice, the researchers said.
Patients with an ASDAS less than 1.3 at baseline had an average progression of 0.71 mSASSS units/2-years. Those with an ASDAS of more than 3.5 at baseline had a progression of 3.1 mSASSS units/2-year progression. A similar relationship was found for BASDAI: patients with a BASDAI less than 4 at baseline had an average progression of 1.4 mSASSS units/2 years, while patients with a BASDAI of 4 or more at baseline had an average progression of 2.7 mSASSS units/2 years.
However, inflammation "by far does not fully explain radiographic damage in AS: Even without measurable disease activity there is still considerable radiographic progression," they said. Patients who have inactive disease for the entire 12 years still can expect a progression of 5 mSASSS units on average. It seems as if increased bone formation in AS is partly constitutive and partly inflammation dependent.
The effect of disease activity on radiographic progression seems to be stronger in men, who had an additional progression of about 1 mSASSS unit per 2-year interval per additional unit of ASDAS. The researchers also found a stronger effect of disease activity on radiographic progression in the early phase of AS.
The models with ASDAS as the disease activity measure fitted the data better than did models with BASDAI, CRP, or BASDAI+CRP. An increase of one ASDAS unit led to an increase of 0.72 mSASSS units/2 years. An ASDAS exceeding 3.5 compared with an ASDAS of less than 1.3 resulted in an additional 2-year progression of 2.31 mSASSS units.
Dr. Romero was supported by the Fundação para a Ciência e Tecnologia (FCT) grant SFRH/BD/68684/2010.
From Annals of Rheumatic Diseases
Key clinical point: New bone formation in ankylosing spondylitis correlates with inflammation.
Major finding: Patients with an ASDAS less than 1.3 at baseline had an average progression of 0.71 mSASSS units/2-years. Those with an ASDAS of more than 3.5 at baseline had a progression of 3.1 mSASSS units/2-year progression.
Data source: A 12-year follow up study of 184 patients in the Outcome in AS International Study (OASIS).
Disclosures: Dr. Romero was supported by the Fundação para a Ciência e Tecnologia (FCT) grant SFRH/BD/68684/2010.