Artikel
Ustekinumab effectively reduces clinical symptoms and active inflammation detected by magnetic resonance imaging in patients with active ankylosing spondylitis: results of a 28-week, prospective, open-label, proof-of-concept study (TOPAS)
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Autoren
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Denis Poddubnyy
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Gastroenterologie, Infektologie, Rheumatologie, Berlin
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Kay-Geert Hermann
- Charité - Universitätsmedizin Berlin, Radiologie, Berlin
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Johanna Callhoff
- Deutsches Rheuma-Forschungszentrum (DRFZ), Forschungsbereich Epidemiologie, Berlin
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Joachim Listing
- Deutsches Rheuma-Forschungszentrum (DRFZ), Forschungsbereich Epidemiologie, Berlin
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Joachim Sieper
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Gastroenterologie, Infektologie, Rheumatologie, Berlin
| Veröffentlicht: | 12. September 2014 |
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Gliederung
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Background: Ustekinumab – a fully human monoclonal antibody against interleukin (IL)-12 and -23 – has been shown to be effective and is approved for treatment of psoriasis and psoriatic arthritis. The purpose of the current study was to investigate the short-term efficacy and safety of ustekinumab in patients with active ankylosing spondylitis (AS).
Methods: In this trial ustekinumab in a dose of 90 mg was administered subcutaneously at baseline, week 4 and week 16 in 20 patients with active AS. Eligible patients were required to have a diagnosis of AS according to the modified New York criteria and an active disease defined as a BASDAI score of ≥4 despite previous NSAIDs treatment. The primary study endpoint was the proportion of patients with ASAS40 response at week 24. Magnetic resonance imaging (MRI) of the sacroiliac joints (SIJ) and of the spine (STIR and T1-weighted sequences) was performed at baseline and at week 24.
Results: At week 24, ASAS40 response was reached by 65% of the patients. ASAS partial remission and a ≥50% improvement of the BASDAI were achieved in 30% and 55% of the patients, respectively (Figure 1 [Fig. 1]). Complete MRI sets (baseline and follow-up) were available in 17 patients. There was a significant reduction of active inflammation on MRI at week 24 as compared to baseline both in the SIJ (osteitis change score -2.2±3.8 corresponding to 41% reduction) and in the spine (osteitis change score -1.2±2.3 corresponding to 31% reduction). Reduction of active inflammation after 24 weeks was more prominent and statistically significant in patients with clinical response (ASAS40): osteitis change score in the SIJ was -3.1±3.8 in responders as compared to +0.6±1.3 in non-responders, p=0.015; similarly, osteitis change score in the spine was -1.9±1.9 in responders as compared to +1.0±2.4 in non-responders, p=0.023.
Overall, ustekinumab was well tolerated: only one serious adverse event (AS worsening) was observed, there were no adverse events leading to study discontinuation, no cases of serious infections, malignancies or deaths.
Conclusion: In this proof-of-concept clinical trial, ustekinumab treatment was associated with a significant reduction of symptoms and of active inflammation in the axial skeleton in patients with active AS.
