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- Chatzidionysiou, Katerina
(author)
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Biological therapy in rheumatoid arthritis : epidemiological studies
- 2014
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Doctoral thesis (other academic/artistic)abstract
- The landscape of RA treatment has unquestionably changed dramatically during the last decade. A deeper understanding of the pathophysiological and immunological mechanisms in RA, earlier and more aggressive treatment, and the development and introduction to daily clinical practice of a new class of antirheumatic drugs, the so-called biologic therapies, has contributed to this ‘revolution’. To date, nine biologic agents have been approved for the treatment for RA and more molecules with distinct mechanisms of action are currently being tested in laboratories and in clinical trials. In all cases, very good clinical efficacy and safety were documented in large, randomized, controlled clinical trials that led to regulatory approval. However, not all questions regarding the optimal use of these agents can be addressed in randomized trials. Observational studies based on registries can provide important information about the effectiveness and safety of biologics in real-life RA populations as well as better insight of different treatment strategies. Thus they are important ‘pieces of the puzzle’ and can help complete the picture of RA treatment. This thesis comprises of two parts: part I is based on four studies about several aspects of rituximab use in RA which are based on a large international cohort. The second part is based on four studies about the use of TNF inhibitors in RA (cycling, switching and discontinuation) which are based on local and national registers and a pilot clinical trial.
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- Chatzidionysiou, Katerina, et al.
(author)
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Effectiveness of TNF inhibitor switch in RA: results from the national Swedish register
- 2014
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 74:5, s. 890-896
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Journal article (peer-reviewed)abstract
- Background Switching to a second tumour necrosis factor inhibitor (TNFi) after discontinuation of a first in rheumatoid arthritis (RA) is a common strategy. The reason for the switch from the first TNFi could potentially influence the response to therapy. Data on direct comparisons between TNFi after switching are limited. Methods The national Swedish register was used. RA patients who switched to a second TNFi (infliximab, etanercept or adalimumab) after failure of a TNFi as first-ever biologic were identified. Effectiveness of treatment was compared across the three drugs according to the first TNFi used, the reason for discontinuing and the drug survival. Drug survival across TNFi used as second biologic was compared. Results Half of all patients starting infliximab, adalimumab or etanercept during the period 2005-2012 discontinued treatment for various reasons. Of these patients, a third switched within 2 months to a second TNFi (infliximab, etanercept or adalimumab). Around 35% of all patients achieved low disease activity or remission at 6 months. Regarding the switching strategy, best results were observed among patients who switched from infliximab to etanercept because of (secondary) inefficacy. Etanercept as second TNFi was associated with longer drug survival compared with infliximab. Conclusions Switching to a second TNFi after the failure of the first may lead to good clinical results. The inter-drug differences in drug survival on the second TNFi mirror those reported previously for the first TNFi, suggesting that these differences are not solely due to channelling bias.
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- van Vollenhoven, Ronald F., et al.
(author)
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Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group Swefot trial
- 2012
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In: The Lancet. - 1474-547X. ; 379:9827, s. 1712-1720
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Journal article (peer-reviewed)abstract
- Background Analysis of the Swedish Farmacotherapy (Swefot) trial at 12 months showed that the addition of an anti-tumour-necrosis-factor agent gave an improved clinical outcome compared with the addition of conventional disease-modifying antirheumatic drugs in patients with methotrexate-refractory early rheumatoid arthritis. Here we report the 2 year follow-up assessment. Methods In this randomised, non-blinded, parallel-group trial, we enrolled adult patients older than 18 years with rheumatoid arthritis and a symptom duration of less than 1 year from 15 rheumatology units in Sweden between December, 2002 and December, 2006. All patients were started on methotrexate. After 3-4 months, those who failed treatment were randomly assigned (1: 1) to group A (conventional treatment; additional sulfasalazine and hydroxychloroquine) or group B (biological treatment; additional infliximab). Randomisation was done with a computer-generated sequence. We analysed clinical outcomes at months 18 and 24 by the response criteria of the American College of Rheumatology and the European League Against Rheumatism, and radiographs of patients' hands and feet at months 12 and 24 using the Van der Heijde modification of the Sharp score. Analysis was by intention to treat. This trial is registered with www.ClinicalTrials.gov, number NCT00764725. Findings Of 493 screened individuals, we enrolled 487, of whom 258 were randomly allocated to treatment. The proportion of patients in group B who received a EULAR-defined good response was non-significantly greater than it was in group A at 18 months (49 of 128 [38%] vs 38 of 130 [29%]) and at 24 months (49 of 128 [38%] vs 40 of 130 [31%]; p=0.204). After 24 months, radiological disease progression was greater in patients in group A than it was in those in group B (mean 7.23 [SD 12.72] vs 4.00 [10.0]; p=0.009). We recorded three serious adverse events: an extended generalised illness in group A, an extended febrile episode in group B, and a generalised illness in group B. Interpretation Additional biological treatment is a valid option for patients who fail initial methotrexate treatment. However, improved clinical outcomes after 12 months and better radiographical results after 24 months should be weighed against the absence of a convincing clinical difference at 24 months and substantially higher costs. Therefore, for many patients who fail initial methotrexate treatment, add-on treatment with disease-modifying antirheumatic drugs is an appropriate treatment option.
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