Biological therapy in rheumatoid arthritis : epidemiological studies

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.

List of scientific papers

I. Chatzidionysiou K, Lie E, Nasonov E, Lukina G, Hetland ML, Tarp U, Gabay C, van Riel PL, Nordström DC, Gomez-Reino J, Pavelka K, Tomsic M, Kvien TK, van Vollenhoven RF. Highest clinical effectiveness of rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonists has failed: pooled data from 10 European registries. Ann Rheum Dis. 2011 Sep; 70(9):1575-80.
https://doi.org/10.1136/ard.2010.148759

II. Chatzidionysiou K, Lie E, Nasonov E, Lukina G, Hetland ML, Tarp U, van Riel PL, Nordström DC, Gomez-Reino J, Pavelka K, Tomsic M, Kvien TK, van Vollenhoven RF, Gabay C. Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and leflunomide in rituximab-treated rheumatoid arthritis patients: results of a 1-year follow-up study from the CERERRA collaboration. Ann Rheum Dis. 2012 Mar; 71(3):374-7.
https://doi.org/10.1136/annrheumdis-2011-200003

III. Chatzidionysiou K, Lie E, Nasonov E, Lukina G, Hetland ML, Tarp U, Ancuta I, Pavelka K, Nordström DC, Gabay C, Canhão H, Tomsic M, van Riel PL, Gomez-Reino J, Kvien TK, van Vollenhoven RF. Effectiveness of two different doses of rituximab for the treatment of RA: data from the CERERRA collaboration. [Manuscript]

IV. Chatzidionysiou K, Lie E, Nasonov E, Lukina G, Hetland ML, Hauge E, Pavelka K, Gabay C, Nordström DC, Canhão H, Tomsic M, van Riel PL, Gomez-Reino J, Ancuta I, Kvien TK, van Vollenhoven RF. Retreatment with rituximab in Rheumatoid Arthritis in a real-life cohort-data from the CERERRA collaboration. [Manuscript]

V. Chatzidionysiou K, Askling J, Eriksson J, Kristensen LE, van Vollenhoven R; for the ARTIS group. Effectiveness of TNF inhibitor switch in RA: results from the national Swedish register. Ann Rheum Dis. 2014 Jan 15.
https://doi.org/10.1136/annrheumdis-2013-204714

VI. Chatzidionysiou K, van Vollenhoven RF. Rituximab versus anti-TNF in patients who previously failed one TNF inhibitor in an observational cohort. Scand J Rheumatol. 2013; 42(3):190-5.
https://doi.org/10.3109/03009742.2012.729607

VII. Chatzidionysiou K, Askling J, Eriksson J, Kristensen LE, van Vollenhoven R. Effectiveness and drug-survival of certolizumab pegol in clinical practice – results from a national registry. [Manuscript]

VIII. Chatzidionysiou K, Turesson C, Teleman A, Knight A, Lindqvist E, Larsson P, Cöster L, van Vollenhoven R, Heimbürger M. A Multicenter, Randomized, Controlled, Open-Label Pilot Study of the Feasibility of Discontinuation of Adalimumab in Rheumatoid Arthritis Patients in Stable Clinical Remission. [Manuscript]