Artikel
Clinical, serologic and radiographic markers during and after the first RCT of Tocilizumab in giant cell arteritis
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Autoren
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Sabine Adler
- Inselspital Bern, Universitätsklinik für Rheumatologie, Immunologie und Allergologie, Bern, Schweiz
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Andrea Gloor
- Universitätsklinik für Rheumatologie, Immunologie und Allergologie, Bern, Schweiz
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Stephan Reichenbach
- Institut für Sozial- und Präventivmedizin, Universität Bern, Bern, Schweiz
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Jennifer Cullmann
- Universitätsinstitut für diagnostische, interventionelle und pädiatrische Radiologie, Universitätsklinik Bern, Bern, Schweiz
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Daniel Yerly
- Universitätsklinik für Rheumatologie, Immunologie und Allergologie, Bern, Schweiz
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Michael Seitz
- Inselspital Bern, Klinik für Rheumatologie & klinische Immunologie, Allergologie, Bern, Schweiz
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Peter M. Villiger
- Inselspital Bern, Klinik für Rheumatologie, klinische Immunologie und Allergologie, Bern, Schweiz
| Veröffentlicht: | 5. Februar 2019 |
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Gliederung
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Background: Giant Cell Arteritis (GCA) is the most frequent large vessel vasculitis (LVV) in Western countries, affecting predominantly women over 50 years of age. Intense inflammation in all layers of the medium- to large-sized arteries and formation of granulomas might lead to vascular obliteration, blindness, aneurysms and aortic ruptures. Conventional treatment with long-term glucocorticoids (GC) leads to side effects over time. Tocilizumab (TCZ) has very recently been proved to maintain remission and to lead to significant reduction of the cumulative GC dose. Data on incidence and prediction of relapse for and during long-term follow-up after stop of TCZ are rare.
Methods: Between 2012 and 2015, 30 patients underwent the first phase 2, randomised, double-blind, placebo-controlled trial (RCT) of TCZ to induce and control remission of GCA with a 12-months cycle of 8mg/kg bodyweight of TCZ given in 4-weekly intervals and concomitant glucocorticoids in rapid decrements. Whereas all but one patient in the TCZ arm stayed in lasting remission up to study end at week 52, only 2 patients in the placebo arm did not relapse. Along the study, sera were collected in order to analyze a large range of immune-inflammatory biomarkers. Furthermore, Magnetic Resonance Angiography (MRA) was repeated if positive at start of study and during follow-up.
Results: After study end patients were followed-up for an average of 48 months after the last dose of TCZ. Relapse occurred in 11/19 patients mostly during the first 6 months without further relapses after month 14.
MMP-3, pentraxin-3 and sTNFR2 were significantly elevated while ICAM-1 and CD163 were significantly decreased initially with almost complete normalization toward the end of study compared to healthy controls (Figure 1 [Fig. 1]). MMP-3 levels showed a weak association with MRA intensity; none of the biomarkers predicted relapse after study end. MRA at last follow-up did not show vascular damage in any of the patients.
Conclusion: A 12-months cycle of i.v. TCZ induces long-term clinical remission in almost 50% of patients and restores specific serological markers of inflammation. MRA is not reliable to monitor disease activity but should be repeated - at least yearly - in order not to miss possible large vessel damage.
