Etanercept Doesn't Slow Structural Ankylosing Spondylitis Progression

AMSTERDAM — Treatment with etanercept for 2 years failed to inhibit structural progression of ankylosing spondylitis in the first controlled study to examine this key issue, Dr. Desiree M. van der Heijde said at the annual European Congress of Rheumatology.

“This suggests there may not be direct linkage between clinical disease activity, inflammation, and new bone formation in ankylosing spondylitis. It might be that syndesmophyte formation is tumor necrosis factor-independent,” added Dr. van der Heijde, professor of rheumatology at University Hospital Maastricht (the Netherlands).

Does etanercept's failure to inhibit structural damage in this study mean that clinicians should narrow their indications for anti-TNF therapy in ankylosing spondylitis (AS) patients? Certainly not, Dr. van der Heijde said.

She pointed out that this study and others have shown that these drugs provide many other worthwhile benefits, including improvement in clinical signs and symptoms, quality of life, and physical function, along with greater bone mineral density and reduced inflammation on MRI.

She reported on 257 AS patients who participated in a 24-week double-blind, placebo-controlled clinical trial of etanercept therapy and then continued on open-label etanercept. Spinal x-rays were taken at baseline and at 2 years, and will be obtained again at 4 years.

The comparison group consisted of 175 patients in the Outcome in Ankylosing Spondylitis International Study (OASIS), none of whom received a TNF inhibitor. The radiographs were analyzed by evaluators blinded to the origin of the films and the time order of the films.

The mean change over 2 years in radiographic structural disease progression as measured by the modified Stokes Ankylosing Spondylitis Spinal Score was 0.91 in the etanercept study participants, which wasn't significantly different from that noted in OASIS subjects, she reported.

Whether etanercept's lack of inhibition of radiographic disease progression is part of a class effect extending to infliximab and adalimumab is unknown. It is worth remembering, however, that the TNF blockers have differential efficacy in Crohn's disease and uveitis, the rheumatologist said.

One implication of this study might be that TNF inhibitors should be utilized much earlier in the disease process, before syndesmophytes have formed.

The idea—which is well worth pursuing in clinical trials, Dr. van der Heijde said—is to suppress inflammation before the structural damage has begun.

Rheumatologists at the University of Leuven (Belgium) have developed a hypothesis she finds attractive. They have shown, in mouse models of AS, that once new bone formation is triggered by inflammation it is a continuing process, even if the inflammation is taken away.

The Belgians have zeroed in on bone morphogenetic proteins as potentially playing a key role in this process.

These proteins are members of the transforming growth factor beta superfamily that induce a cascade of out-of-control bone formation. As such, bone morphogenetic protein signalling may be a potential new therapeutic target, she said.

Several audience members criticized Dr. van der Heijde's reliance upon historical controls from OASIS in the etanercept study. She replied that today a 2-year placebo-controlled trial of TNF blockers in AS patients is no longer ethical.

Dr. Robert D.M. Landewé commented that he considered Dr. van der Heijde's study “one of the most important presentations of the whole congress.”

The idea is to suppress inflammation before the structural damage has begun. DR. VAN DER HEIJDE

AMSTERDAM — Treatment with etanercept for 2 years failed to inhibit structural progression of ankylosing spondylitis in the first controlled study to examine this key issue, Dr. Desiree M. van der Heijde said at the annual European Congress of Rheumatology.

“This suggests there may not be direct linkage between clinical disease activity, inflammation, and new bone formation in ankylosing spondylitis. It might be that syndesmophyte formation is tumor necrosis factor-independent,” added Dr. van der Heijde, professor of rheumatology at University Hospital Maastricht (the Netherlands).

Does etanercept's failure to inhibit structural damage in this study mean that clinicians should narrow their indications for anti-TNF therapy in ankylosing spondylitis (AS) patients? Certainly not, Dr. van der Heijde said.

She pointed out that this study and others have shown that these drugs provide many other worthwhile benefits, including improvement in clinical signs and symptoms, quality of life, and physical function, along with greater bone mineral density and reduced inflammation on MRI.

She reported on 257 AS patients who participated in a 24-week double-blind, placebo-controlled clinical trial of etanercept therapy and then continued on open-label etanercept. Spinal x-rays were taken at baseline and at 2 years, and will be obtained again at 4 years.

The comparison group consisted of 175 patients in the Outcome in Ankylosing Spondylitis International Study (OASIS), none of whom received a TNF inhibitor. The radiographs were analyzed by evaluators blinded to the origin of the films and the time order of the films.

The mean change over 2 years in radiographic structural disease progression as measured by the modified Stokes Ankylosing Spondylitis Spinal Score was 0.91 in the etanercept study participants, which wasn't significantly different from that noted in OASIS subjects, she reported.

Whether etanercept's lack of inhibition of radiographic disease progression is part of a class effect extending to infliximab and adalimumab is unknown. It is worth remembering, however, that the TNF blockers have differential efficacy in Crohn's disease and uveitis, the rheumatologist said.

One implication of this study might be that TNF inhibitors should be utilized much earlier in the disease process, before syndesmophytes have formed.

The idea—which is well worth pursuing in clinical trials, Dr. van der Heijde said—is to suppress inflammation before the structural damage has begun.

Rheumatologists at the University of Leuven (Belgium) have developed a hypothesis she finds attractive. They have shown, in mouse models of AS, that once new bone formation is triggered by inflammation it is a continuing process, even if the inflammation is taken away.

The Belgians have zeroed in on bone morphogenetic proteins as potentially playing a key role in this process.

These proteins are members of the transforming growth factor beta superfamily that induce a cascade of out-of-control bone formation. As such, bone morphogenetic protein signalling may be a potential new therapeutic target, she said.

Several audience members criticized Dr. van der Heijde's reliance upon historical controls from OASIS in the etanercept study. She replied that today a 2-year placebo-controlled trial of TNF blockers in AS patients is no longer ethical.

Dr. Robert D.M. Landewé commented that he considered Dr. van der Heijde's study “one of the most important presentations of the whole congress.”

The idea is to suppress inflammation before the structural damage has begun. DR. VAN DER HEIJDE

AMSTERDAM — Treatment with etanercept for 2 years failed to inhibit structural progression of ankylosing spondylitis in the first controlled study to examine this key issue, Dr. Desiree M. van der Heijde said at the annual European Congress of Rheumatology.

“This suggests there may not be direct linkage between clinical disease activity, inflammation, and new bone formation in ankylosing spondylitis. It might be that syndesmophyte formation is tumor necrosis factor-independent,” added Dr. van der Heijde, professor of rheumatology at University Hospital Maastricht (the Netherlands).

Does etanercept's failure to inhibit structural damage in this study mean that clinicians should narrow their indications for anti-TNF therapy in ankylosing spondylitis (AS) patients? Certainly not, Dr. van der Heijde said.

She pointed out that this study and others have shown that these drugs provide many other worthwhile benefits, including improvement in clinical signs and symptoms, quality of life, and physical function, along with greater bone mineral density and reduced inflammation on MRI.

She reported on 257 AS patients who participated in a 24-week double-blind, placebo-controlled clinical trial of etanercept therapy and then continued on open-label etanercept. Spinal x-rays were taken at baseline and at 2 years, and will be obtained again at 4 years.

The comparison group consisted of 175 patients in the Outcome in Ankylosing Spondylitis International Study (OASIS), none of whom received a TNF inhibitor. The radiographs were analyzed by evaluators blinded to the origin of the films and the time order of the films.

The mean change over 2 years in radiographic structural disease progression as measured by the modified Stokes Ankylosing Spondylitis Spinal Score was 0.91 in the etanercept study participants, which wasn't significantly different from that noted in OASIS subjects, she reported.

Whether etanercept's lack of inhibition of radiographic disease progression is part of a class effect extending to infliximab and adalimumab is unknown. It is worth remembering, however, that the TNF blockers have differential efficacy in Crohn's disease and uveitis, the rheumatologist said.

One implication of this study might be that TNF inhibitors should be utilized much earlier in the disease process, before syndesmophytes have formed.

The idea—which is well worth pursuing in clinical trials, Dr. van der Heijde said—is to suppress inflammation before the structural damage has begun.

Rheumatologists at the University of Leuven (Belgium) have developed a hypothesis she finds attractive. They have shown, in mouse models of AS, that once new bone formation is triggered by inflammation it is a continuing process, even if the inflammation is taken away.

The Belgians have zeroed in on bone morphogenetic proteins as potentially playing a key role in this process.

These proteins are members of the transforming growth factor beta superfamily that induce a cascade of out-of-control bone formation. As such, bone morphogenetic protein signalling may be a potential new therapeutic target, she said.

Several audience members criticized Dr. van der Heijde's reliance upon historical controls from OASIS in the etanercept study. She replied that today a 2-year placebo-controlled trial of TNF blockers in AS patients is no longer ethical.

Dr. Robert D.M. Landewé commented that he considered Dr. van der Heijde's study “one of the most important presentations of the whole congress.”

The idea is to suppress inflammation before the structural damage has begun. DR. VAN DER HEIJDE