Switching TNF Inhibitors Pays in Ankylosing Spondylitis

BERLIN – If at first you don’t succeed in getting satisfactory results when prescribing a tumor necrosis factor inhibitor in ankylosing spondylitis, don’t hesitate to switch to another. And, if need be, switch again. And again.

"Irrespective of the reason for discontinuation of the first [tumor necrosis factor (TNF)] inhibitor, switching to another TNF inhibitor should be considered," said Dr. Bente Glintborg of Gentofte University Hospital, Copenhagen, at the annual European Congress of Rheumatology.

That’s her key message gleaned from DANBIO, the Danish national registry of patients on biologic agents for rheumatic diseases. DANBIO is a comprehensive registry reflecting real-world clinical practice. Physician reporting to the registry is mandatory, with no informed consent requirement.

Dr. Glintborg reported on 1,436 ankylosing spondylitis (AS) patients followed for a median of 2.4 years after going on their first TNF inhibitor and enrolling in DANBIO.

The first key lesson from DANBIO is that switching anti-TNF biologics in patients with AS is common. Of DANBIO participants, 30% switched to a different TNF inhibitor. Changes made due to lack of efficacy outnumbered those due to adverse events by 2 to 1.

A total of 137 patients, or 10% of the original cohort, switched again to a third TNF inhibitor. This time around, changes made because of lack of efficacy outpaced those due to adverse events by 3 to 1. Thirty-nine patients went on to switch to a fourth TNF inhibitor.

Switchers were disproportionately female, and had an average disease duration several years less briefer than that of nonswitchers. They also had greater baseline disease activity by a variety of measures.

Each successive switch to a different TNF inhibitor brought a yet-lower favorable clinical response rate. Nevertheless, 2 years after embarking on anti-TNF therapy, 52% of switchers enjoyed a good clinical response as defined by at least a 50% decrease from baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI), as did 63% of nonswitchers. The number needed to treat in order to obtain a good clinical response was 1.6 among nonswitchers and 1.9 for switchers.

The favorable clinical response rate after 6 months on a TNF inhibitor was 59% during the first treatment course, 41% during the second, and 32% with the third. The number needed to treat was 1.7, 2.4, and 3.0, respectively, she reported.

The median duration on first-line anti-TNF therapy was 3.1 years, falling to 1.6 years for a second course and 1.8 years with a third.

Male gender and a low baseline BASFI were significant predictors of longer adherence to the second TNF inhibitor prescribed. Among the many factors that proved unrelated to adherence were the specific anti-TNF agent, baseline C-reactive protein level, presence or absence of concomitant methotrexate, and the reason for stopping the first TNF inhibitor.

Infliximab (Remicade) was the most frequently prescribed first-line agent among Danish AS patients. A total of 45% of patients received it. The next most popular first-line TNF inhibitors were adalimumab (Humira), given to 37%, and etanercept (Enbrel), at 16%. Adalimumab was the second-line agent selected in 46% of first-time switchers, followed by etanercept in 40% and infliximab in 10%.

Session cochair Dr. Martin Rudwaleit expressed appreciation for the Danish effort to shed light on the sequential use of TNF inhibitors in AS, a heretofore understudied subject.

"I think it’s very good news to hear that switching can be quite effective, as you have shown in this open registry, particularly in light of not having any other compounds available at the moment to give to these patients," commented Dr. Rudwaleit of Charité University Hospital, Berlin.

Dr. Glintborg reported having no financial conflicts.

BERLIN – If at first you don’t succeed in getting satisfactory results when prescribing a tumor necrosis factor inhibitor in ankylosing spondylitis, don’t hesitate to switch to another. And, if need be, switch again. And again.

"Irrespective of the reason for discontinuation of the first [tumor necrosis factor (TNF)] inhibitor, switching to another TNF inhibitor should be considered," said Dr. Bente Glintborg of Gentofte University Hospital, Copenhagen, at the annual European Congress of Rheumatology.

That’s her key message gleaned from DANBIO, the Danish national registry of patients on biologic agents for rheumatic diseases. DANBIO is a comprehensive registry reflecting real-world clinical practice. Physician reporting to the registry is mandatory, with no informed consent requirement.

Dr. Glintborg reported on 1,436 ankylosing spondylitis (AS) patients followed for a median of 2.4 years after going on their first TNF inhibitor and enrolling in DANBIO.

The first key lesson from DANBIO is that switching anti-TNF biologics in patients with AS is common. Of DANBIO participants, 30% switched to a different TNF inhibitor. Changes made due to lack of efficacy outnumbered those due to adverse events by 2 to 1.

A total of 137 patients, or 10% of the original cohort, switched again to a third TNF inhibitor. This time around, changes made because of lack of efficacy outpaced those due to adverse events by 3 to 1. Thirty-nine patients went on to switch to a fourth TNF inhibitor.

Switchers were disproportionately female, and had an average disease duration several years less briefer than that of nonswitchers. They also had greater baseline disease activity by a variety of measures.

Each successive switch to a different TNF inhibitor brought a yet-lower favorable clinical response rate. Nevertheless, 2 years after embarking on anti-TNF therapy, 52% of switchers enjoyed a good clinical response as defined by at least a 50% decrease from baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI), as did 63% of nonswitchers. The number needed to treat in order to obtain a good clinical response was 1.6 among nonswitchers and 1.9 for switchers.

The favorable clinical response rate after 6 months on a TNF inhibitor was 59% during the first treatment course, 41% during the second, and 32% with the third. The number needed to treat was 1.7, 2.4, and 3.0, respectively, she reported.

The median duration on first-line anti-TNF therapy was 3.1 years, falling to 1.6 years for a second course and 1.8 years with a third.

Male gender and a low baseline BASFI were significant predictors of longer adherence to the second TNF inhibitor prescribed. Among the many factors that proved unrelated to adherence were the specific anti-TNF agent, baseline C-reactive protein level, presence or absence of concomitant methotrexate, and the reason for stopping the first TNF inhibitor.

Infliximab (Remicade) was the most frequently prescribed first-line agent among Danish AS patients. A total of 45% of patients received it. The next most popular first-line TNF inhibitors were adalimumab (Humira), given to 37%, and etanercept (Enbrel), at 16%. Adalimumab was the second-line agent selected in 46% of first-time switchers, followed by etanercept in 40% and infliximab in 10%.

Session cochair Dr. Martin Rudwaleit expressed appreciation for the Danish effort to shed light on the sequential use of TNF inhibitors in AS, a heretofore understudied subject.

"I think it’s very good news to hear that switching can be quite effective, as you have shown in this open registry, particularly in light of not having any other compounds available at the moment to give to these patients," commented Dr. Rudwaleit of Charité University Hospital, Berlin.

Dr. Glintborg reported having no financial conflicts.

BERLIN – If at first you don’t succeed in getting satisfactory results when prescribing a tumor necrosis factor inhibitor in ankylosing spondylitis, don’t hesitate to switch to another. And, if need be, switch again. And again.

"Irrespective of the reason for discontinuation of the first [tumor necrosis factor (TNF)] inhibitor, switching to another TNF inhibitor should be considered," said Dr. Bente Glintborg of Gentofte University Hospital, Copenhagen, at the annual European Congress of Rheumatology.

That’s her key message gleaned from DANBIO, the Danish national registry of patients on biologic agents for rheumatic diseases. DANBIO is a comprehensive registry reflecting real-world clinical practice. Physician reporting to the registry is mandatory, with no informed consent requirement.

Dr. Glintborg reported on 1,436 ankylosing spondylitis (AS) patients followed for a median of 2.4 years after going on their first TNF inhibitor and enrolling in DANBIO.

The first key lesson from DANBIO is that switching anti-TNF biologics in patients with AS is common. Of DANBIO participants, 30% switched to a different TNF inhibitor. Changes made due to lack of efficacy outnumbered those due to adverse events by 2 to 1.

A total of 137 patients, or 10% of the original cohort, switched again to a third TNF inhibitor. This time around, changes made because of lack of efficacy outpaced those due to adverse events by 3 to 1. Thirty-nine patients went on to switch to a fourth TNF inhibitor.

Switchers were disproportionately female, and had an average disease duration several years less briefer than that of nonswitchers. They also had greater baseline disease activity by a variety of measures.

Each successive switch to a different TNF inhibitor brought a yet-lower favorable clinical response rate. Nevertheless, 2 years after embarking on anti-TNF therapy, 52% of switchers enjoyed a good clinical response as defined by at least a 50% decrease from baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI), as did 63% of nonswitchers. The number needed to treat in order to obtain a good clinical response was 1.6 among nonswitchers and 1.9 for switchers.

The favorable clinical response rate after 6 months on a TNF inhibitor was 59% during the first treatment course, 41% during the second, and 32% with the third. The number needed to treat was 1.7, 2.4, and 3.0, respectively, she reported.

The median duration on first-line anti-TNF therapy was 3.1 years, falling to 1.6 years for a second course and 1.8 years with a third.

Male gender and a low baseline BASFI were significant predictors of longer adherence to the second TNF inhibitor prescribed. Among the many factors that proved unrelated to adherence were the specific anti-TNF agent, baseline C-reactive protein level, presence or absence of concomitant methotrexate, and the reason for stopping the first TNF inhibitor.

Infliximab (Remicade) was the most frequently prescribed first-line agent among Danish AS patients. A total of 45% of patients received it. The next most popular first-line TNF inhibitors were adalimumab (Humira), given to 37%, and etanercept (Enbrel), at 16%. Adalimumab was the second-line agent selected in 46% of first-time switchers, followed by etanercept in 40% and infliximab in 10%.

Session cochair Dr. Martin Rudwaleit expressed appreciation for the Danish effort to shed light on the sequential use of TNF inhibitors in AS, a heretofore understudied subject.

"I think it’s very good news to hear that switching can be quite effective, as you have shown in this open registry, particularly in light of not having any other compounds available at the moment to give to these patients," commented Dr. Rudwaleit of Charité University Hospital, Berlin.

Dr. Glintborg reported having no financial conflicts.