There are 2 groups of drugs that have been shown effective in the treatment of patients with axial spondyloarthritis: nonsteroidal anti-inflammatory drugs and tumor necrosis factor α blockers. Conventional disease-modifying drugs and some other biologics have not been shown clinically efficacious in this disease. This overview discusses the available data on whether early treatment strategies in patients with axial spondyloarthritis have an effect on (1) the percentage of patients reaching clinical remission, (2) achieving drug-free remission, and (3) the progress of radiographic progression in the spine as a parameter for structural damage.
- •
Patients with axial spondyloarthritis respond best to TNF-blocker therapy if treated early in the course of their disease. Patients seem also to respond better to NSAiDs if treated early.
- •
There is currently no clear evidence that early therapeutic intervention is mandatory in axial SpA to,prevent structural damage. More research is needed in this area. NSAIDs seem to prevent sturctural damage in established ankylosing spondylitis.
Introduction
Currently there are mainly 2 groups of drugs that have been shown effective in the treatment of patients with axSpA, NSAIDs and TNF-α blockers, which have been approved for those patients who do not adequately respond to NSAID treatment. Conventional disease-modifying antirheumatic drugs and some other biologics, such as anakinra and abatacept, have not been shown so far to be clinically efficacious in this disease.
Most of the early treatment trials in axSpA have been performed in patients with ankylosing spondylitis (AS) classified according to the modified New York criteria—implying that patients already had structural changes in the SI joints (radiographic sacroiliitis). The mean symptom duration of patients included in treatment trials both with NSAIDs and TNF blockers has been between 10 and 14 years. Although short symptom duration and young age have been identified as parameters predictive of good response rates, there were, until recently, no data available addressing the question of whether axSpA patients respond better when treated earlier. The development of the ASAS classification criteria for axSpA was a big step forward in that regard because they allow including patients in treatment trials at an early phase of their disease before the occurrence of radiographic changes in the SI joints. This group has recently be termed as nonradiographic axSpA (nr-axSpA). The ASAS classification criteria for the whole group of axSpA are fulfilled if patients have chronic back pain greater than 3 months, if symptoms start at an age younger than 45 years, and if they have either active inflammation in the SI joints on MRI plus 1 additional clinical or laboratory feature typical of SpA, or if they are positive for HLA-B27 plus 2 additional other SpA features.
This overview discusses the available data on whether early treatment strategies in patients with axSpA have an effect on (1) the percentage of patients reaching clinical remission, (2) achieving drug-free remission, and (3) the progress of radiographic progression in the spine as a parameter for structural damage.
The effect of anti-TNF therapy on clinical parameters depends on symptom duration
This article focuses on clinical remission rates according to the ASAS definition but also reports on Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50% and/or ASAS 40% response rates if data on remission are not available. These data are summarized in Table 1 . Clinical remission was reached in TNF blocker trials in approximately 25% of patients with established AS, but AS patients with a symptom duration of less than 10 years showed a better response rate than patients with a symptom duration of between 10 and 20 or more years. In another analysis of an open-label AS trial, remission was reached in 50% of patients younger than 30 years in contrast to only 19% of patients between the age of 40 and 49 years, whereas young age as predictor of a good response was largely overlapping with short symptom duration.
| Name of Study | Treatment a | Subgroup | No. of Patients | Symptom Duration | Clinical Remission (%) a , b | BASDAI 50 or ASAS 40 (%) b | Ref. |
|---|---|---|---|---|---|---|---|
| ASSERT | Infliximab | AS | 201 | 7.7 | 22.4 | ||
| ATLAS | Adalimumab | AS | 208 | 11.3 | 22.1 | ||
| International etanercept study | Etanercept | AS | 138 | 10.1 | 17 | ||
| Infliximab Etanercept | AS | 99 | 14.8 | 56 73 58 31 | ||
| Adalimumab | nr-axSpr | 22 | 7 | 22.7 50 16 | 54.5 | |
| ESTHER | Etanercept | axSpA c | 40 | <5 y | 50 | ||
| Leeds axSpA study | Infliximab | axSpA c | 20 | <3 y | 55.6 | ||
| Adalimumab | nr-axSpA | 91 | 10.1 | 16 | 36 48 31 | |
| INFAST | Infliximab | axSpA c | 105 | <3 y | 61.9 |
a Patients were treated between 12 and 52 weeks.
b According to the ASAS definition.
The first TNF blocker trial in patients with nr-axSpA was performed with adalimumab in the usual dosage (40 mg subcutaneous every 2 weeks). Although these patients did not yet fulfill the modified New York criteria for radiographic sacroiliitis, the mean symptom duration was still 7 to 8 years. Remission was reached in 22.7% (in comparison to 0% in the placebo group)—a percentage similar to the 22.1% of patients in the AS treatment trial with adalimumab. The remission rate went up to 50%, however, when concentrating on the patients with symptom duration less than 3 years—which was considerably higher than the 16% in those with symptom duration greater than 3 years. A larger, phase III trial with 185 nr-axSpA patients treated with adalimumab (using the same dosing) or placebo for 12 weeks followed. Again, the mean symptom duration at inclusion was approximately 10 years. An ASAS 40 response rate was achieved in 36.3% of the adalimumab-treated patients versus 14.9% in the placebo group. The difference between the 2 groups, however, was larger in the subgroup of patients with less than 5 years symptom duration: 49% versus 6%, compared with 31% versus 20%, in patients with symptom duration greater than 5 years, respectively. In another study performed in the United Kingdom with infliximab (5 mg/kg 4 times intravenously until week 12), axSpA patients were included if the symptom duration was less than 3 years, if they had active inflammation in the SI joints detected by MRI, and if they complained about inflammatory back pain and were HLA-B27 positive. Only approximately 12% of these patients already had radiographic sacroiliitis. The remission rate at week 16 in these patients with short symptom duration and a positive MRI was as high as 55.6% versus 12.5% in the placebo group. In another nonblinded but prospective randomized head-to-head trial performed within axSpA patients who had a symptom duration less than 5 years and a positive MRI at inclusion, the remission rate was 50% after 1 year of treatment with etanercept (50mg per week s.c) versus 19% in the group treated with sulfasazine. Half of these patients did not have radiographic sacroiliitis and could thus be labeled as having nr-axSpA, whereas the other half already had structural changes. The symptom duration and the baseline disease activity were similar in both groups. The observation that the response rate was similar in these 2 groups indicates that presence or absence of radiographic sacroiliitis does not matter regarding the response rate if the other parameters are similar.
In a recent treatment trial (Infliximab as First line Therapy in Patients with Early Active Spondyloarthritis Trial [INFAST]), axSpA patients with a symptom duration of less than 3 years, who were not allowed to be included when they had already been refractory to NSAIDs, were treated blindly for 28 weeks either with infliximab (5 mg/kg in the usual sequence of dosing) plus naproxen (1000 mg/d) or just with naproxen plus placebo. In this study the, until now, highest remission rate was achieved in the group treated with both compounds: 62% versus 35% in the group treated with naproxen only.
The effect of anti-TNF therapy on clinical parameters depends on symptom duration
This article focuses on clinical remission rates according to the ASAS definition but also reports on Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50% and/or ASAS 40% response rates if data on remission are not available. These data are summarized in Table 1 . Clinical remission was reached in TNF blocker trials in approximately 25% of patients with established AS, but AS patients with a symptom duration of less than 10 years showed a better response rate than patients with a symptom duration of between 10 and 20 or more years. In another analysis of an open-label AS trial, remission was reached in 50% of patients younger than 30 years in contrast to only 19% of patients between the age of 40 and 49 years, whereas young age as predictor of a good response was largely overlapping with short symptom duration.
| Name of Study | Treatment a | Subgroup | No. of Patients | Symptom Duration | Clinical Remission (%) a , b | BASDAI 50 or ASAS 40 (%) b | Ref. |
|---|---|---|---|---|---|---|---|
| ASSERT | Infliximab | AS | 201 | 7.7 | 22.4 | ||
| ATLAS | Adalimumab | AS | 208 | 11.3 | 22.1 | ||
| International etanercept study | Etanercept | AS | 138 | 10.1 | 17 | ||
| Infliximab Etanercept | AS | 99 | 14.8 | 56 73 58 31 | ||
| Adalimumab | nr-axSpr | 22 | 7 | 22.7 50 16 | 54.5 | |
| ESTHER | Etanercept | axSpA c | 40 | <5 y | 50 | ||
| Leeds axSpA study | Infliximab | axSpA c | 20 | <3 y | 55.6 | ||
| Adalimumab | nr-axSpA | 91 | 10.1 | 16 | 36 48 31 | |
| INFAST | Infliximab | axSpA c | 105 | <3 y | 61.9 |
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
