Off-Label Use Of Rituximab For Systemic Lupus Erythematosus in Europe: Limited Use Mostly In Refractory Patients

Ronald F. van Vollenhoven¹, Melinda Mild², Andrea Doria³, T. Dörner⁴, Gianfranco Ferraccioli⁵, Frederic Houssiau⁶, T.W.J. Huizinga⁷, David A. Isenberg⁸, László Kovács⁹, Guillermo Ruiz-Irastorza¹⁰, Danilo Squatrito¹¹, Alexandre Voskuyl¹², Marta Mosca¹³, G D Sebastiani¹⁴, Murat Inanç¹⁵, Gabriella Szücs¹⁶, Søren Jacobsen¹⁷, A. Castro¹⁸ and for The IRBIS-EMA group¹⁹, ¹Unit for Clinical Therapy Research, Inflammatory Diseases (ClinTRID), the Karolinska Institute, Stockholm, Sweden, ²Department of medicine, Karolinska Institutet, Stockholm, Sweden, ³Rheumatology Unit - Department of Medicine, University of Padova, Padova, Italy, ⁴Charité University Medicine Berlin, Berlin, Germany, ⁵Division of Rheumatology, Institute of Rheumatology and Affine Sciences, Catholic University of the Sacred Heart, Rome, Italy, ⁶Department of Rheumatology, Université catholique de Louvain, Brussels, Belgium, ⁷Rheumatology, Leiden University Medical Center, Leiden, Netherlands, ⁸Centre for Rheumatology Research, Rayne Building, 4th Floor, Centre for Rheumatology, Department of Medicine, University College London, London, United Kingdom, ⁹Department of Rheumatology, University of Szeged, Szeged, Hungary, ¹⁰Autoimmune Diseases Research Unit, Department of Internal Medicine, BioCruces Health Research Institute, Hospital Universitario Cruces, University of the Basque Country, Barakaldo, Spain, ¹¹Center for Autoimmune Diseases, Department of Internal Medicine, Careggi Hospital- Florence, Florence, Italy, ¹²Department of Rheumatology, VU University Medical Center, Amsterdam, Netherlands, ¹³Rheumatology Unit, University of Pisa, Pisa, Italy, ¹⁴Rheumatology Unit, San Camillo-Forlanini Hospital, Rome, Rome, Italy, ¹⁵Department of Internal Medicine, Rheumatology Division, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey, ¹⁶Department of Rheumatology, University of Debrecen Medical and Health Sciences Center, Debrecen, Hungary, ¹⁷Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, ¹⁸Hospital Universitari de Reus, Spain, Reus, Spain, ¹⁹ClinTRID, Department of Medicine, Karolinska Institute, Stockholm, Sweden

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: rituximab and treatment, SLE

Session Information

Title: Systemic Lupus Erythematosus - Clinical Aspects II: Central Nervous System Manifestations, Therapeutics

Session Type: Abstract Submissions (ACR)

Background/Purpose: Rituximab (Rituxan, Mabthera; RTX) has not been approved for use in SLE, but uncontrolled observations have suggested efficacy in some patients and the medication can be used off-label in many European countries. We previously reported that based on data from the IRBIS registry and additional data from investigators, between 0.5 and 1.3% of European patients with SLE have been treated, off-label, with RTX. The objective for this study was to compare characteristics of SLE patients treated off-label with RTX to those of SLE patients treated with conventional, non-biological immunosuppressives (ISs) at the same specialty centers.

Methods: Investigators participating in the International Registry for Biologics in SLE (IRBIS), which was initiated by the SLICC group, provided the data for this study. Data previously submitted to the IRBIS registry by 28 centers in 11 European countries were complemented with additional clinical information from the participating sites. Comparator patients had been started on any conventional IS but were not necessarily naïve for this.

Results: 175 patients were analyzed; 103 were treated off-label with RTX and 72 with a conventional IS. The most frequently used ISs were mycophenolate mofetil (43%) and azathioprine (33%). For both groups, about 90% were female, 90% were Caucasians and 85% were non-smokers. Organ manifestations leading to treatment with RTX were lupus nephritis in 58%, hematological lupus in 16%, musculoskeletal manifestations in 11%, skin disease in 6%, CNS lupus in 7%, and other manifestations in 7%. For patients started on conventional ISs the corresponding percentages were 53%, 11%, 22%, 6%, 7%, and 6%. These distributions were not statistically different. Reason for treatment initiation with RTX was mainly disease control while steroid sparing was frequently the main reason for conventional ISs. At treatment initiation mean disease duration (±SD) was 9.1±7.0 for RTX-treated patients and 4.1±6.6 for patients on ISs (p<0.0001) and mean ages were 41.2±12.5 and 36.1±11.3, respectively (p=0.007). There were significant differences between the groups for SLEDAI scores (12.2±7.0 vs. 9.4±7.0; p=0.001) and SLICC damage index (1.6±3.4 vs. 0.57±1.0, p=0.014).

Conclusion: Both RTX and conventional ISs are mostly used for lupus nephritis, and no other specific organ manifestation was more likely to be treated with RTX. However, patients started on RTX were somewhat older, had significantly longer disease duration, higher disease activity and more damage compared to patients started on conventional ISs only. These data support the view that RTX is used for selected patients with later-stage, more severe SLE.

Disclosure:

R. F. van Vollenhoven,

AbbVie, BMS, GSK, Merck, Pfizer, Roche, UCB,

AbbVie, AstraZeneca, Biotest, BMS, GSK, Lilly, Merck, Pfizer, Roche, UCB, Vertex,

M. Mild,
None;

A. Doria,
None;

T. Dörner,
None;

G. Ferraccioli,
None;

F. Houssiau,

UCB Pharma,

T. W. J. Huizinga,

TWJ Huizinga has received lecture fees/consultancy fees from Merck, UCB, Bristol Myers Squibb, Biotest AG, Pfizer, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Nycomed, Boeringher, Takeda, and Eli Lilly,

D. A. Isenberg,

I have consulted for a number of companiews including GSK, Roche, UCB and teva. I arrange for the payments offered to go a local arthritis charity .,

L. Kovács,
None;

G. Ruiz-Irastorza,
None;

D. Squatrito,
None;

A. Voskuyl,
None;

M. Mosca,
None;

G. D. Sebastiani,
None;

M. Inanç,
None;

G. Szücs,
None;

S. Jacobsen,
None;

A. Castro,
None;

F. T. IRBIS-EMA group,
None.

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