Treating Ankylosing Spondylitis Refractory to TNF-inhibition
SSZ or methotrexate is recommended for patients with AS and peripheral arthritis according to the ASAS recommendations. The effect of SSZ in patients with nonradiographic axial (formerly undifferentiated) SpA has been studied in two recent trials following a trial in 2006. In the current trials, SSZ was directly compared to the TNF receptor fusion protein etanercept (ETN).
In the Ankylosing Spondylitis Study Comparing Enbrel With Sulfasalazine Dosed Weekly trial, ETN 50mg once weekly were compared to SSZ titrated to a maximum of 3 g/day. The proportion of ASAS20 responders at week 16 was significantly greater among patients treated with ETN compared with SSZ (76 vs. 53%, P<0.0001), and this effect on both axial and peripheral manifestations was already marked early.
In ESTHER, whole body MRI was chosen as primary outcome parameter. In the ETN group, the reduction of the SIJ score from 7.7 at baseline to 2.0 was significantly (P=0.02) larger compared with the SSZ group (5.4–3.5) at week 48. A similar difference in the reduction of inflammation was found in the spine from 2.2 to 1.0 in the ETN vs. 1.4–1.3 in the SSZ group between baseline and week 48, respectively (P=0.01). The number of enthesitic sites also improved significantly from 26 to 11 on ETN but not on SSZ. Overall, 50% of patients reached clinical remission in the ETN vs. 19% in the SSZ group at week 48. The imaging data of baseline and the follow-up period showed a close interaction between inflammation, TNF blockade and development of fatty lesions. If baseline inflammation resolved, fatty lesions occured more often in SIJ quadrants and in the spine, but if inflammation did not resolve over 1 year, fatty lesions occurred less frequently.
Taken together, the good response to the TNF blocker could of course have been expected, whereas the relatively good response to SSZ was not. Overall, there seems to be 'some response', at least as good as placebo treatment.
Sulfasalazine
SSZ or methotrexate is recommended for patients with AS and peripheral arthritis according to the ASAS recommendations. The effect of SSZ in patients with nonradiographic axial (formerly undifferentiated) SpA has been studied in two recent trials following a trial in 2006. In the current trials, SSZ was directly compared to the TNF receptor fusion protein etanercept (ETN).
In the Ankylosing Spondylitis Study Comparing Enbrel With Sulfasalazine Dosed Weekly trial, ETN 50mg once weekly were compared to SSZ titrated to a maximum of 3 g/day. The proportion of ASAS20 responders at week 16 was significantly greater among patients treated with ETN compared with SSZ (76 vs. 53%, P<0.0001), and this effect on both axial and peripheral manifestations was already marked early.
In ESTHER, whole body MRI was chosen as primary outcome parameter. In the ETN group, the reduction of the SIJ score from 7.7 at baseline to 2.0 was significantly (P=0.02) larger compared with the SSZ group (5.4–3.5) at week 48. A similar difference in the reduction of inflammation was found in the spine from 2.2 to 1.0 in the ETN vs. 1.4–1.3 in the SSZ group between baseline and week 48, respectively (P=0.01). The number of enthesitic sites also improved significantly from 26 to 11 on ETN but not on SSZ. Overall, 50% of patients reached clinical remission in the ETN vs. 19% in the SSZ group at week 48. The imaging data of baseline and the follow-up period showed a close interaction between inflammation, TNF blockade and development of fatty lesions. If baseline inflammation resolved, fatty lesions occured more often in SIJ quadrants and in the spine, but if inflammation did not resolve over 1 year, fatty lesions occurred less frequently.
Taken together, the good response to the TNF blocker could of course have been expected, whereas the relatively good response to SSZ was not. Overall, there seems to be 'some response', at least as good as placebo treatment.
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