Biologics in myelodysplastic syndrome-related systemic inflammatory and autoimmune diseases: French multicenter retrospective study of 29 patients.

Abstract

BACKGROUND:

Systemic inflammatory and autoimmune diseases (SIADs) associated with myelodysplastic syndromes are often difficult to treat. Corticosteroids are efficient but only usually at high doses. The use of biologics needs to be specified.

METHODS:

In a French multicenter retrospective study, we analyzed the efficacy and safety of biologics (tumor necrosis factor-α [TNF-α] antagonists, tocilizumab, rituximab and anakinra) for SIADs associated with myelodysplastic syndromes (MDSs). Clinical, biological and overall treatment responses were evaluated. When several lines of treatment were used, data were analyzed before and at the end of each treatment line and were pooled to compare overall response among steroids, disease-modifying anti-rheumatic drugs (DMARDs) and biologics.

RESULTS:

We included 29 patients (median age 67years [interquartile range 62-76], 83% males) with MDS-related SIADs treated with at least one biologic. The MDSs were predominantly refractory anemia with excess blasts 1 (38%) and refractory cytopenia with multilineage dysplasia (21%). The SIADs were mainly arthritis (n=6; 20%), relapsing polychondritis (n=8; 30%) and vasculitis (n=10; 34%). During a 3-year median follow-up (IQR 1.3-4.5), a total of 114 lines of treatments were used for all patients: steroids alone (22%), DMARDs (23%), TNF-α antagonists (14%), anakinra (10%), rituximab (10%), tocilizumab (7%) and azacytidine (9%). Considering all 114 lines, overall response (complete and partial) was shown in 54% cases. Overall response was more frequent with steroids (78%) and rituximab (66%) than DMARDs (45%) and other biologics (33%) (p<0.05). Rituximab had better response in vasculitis and TNF-α antagonists in arthritis. During follow-up, 20 patients (71%) presented at least one severe infection.

CONCLUSION:

This nationwide study demonstrates the efficacy of steroids for SIAD-associated MDSs but a high frequency of steroid dependence. The response to biologics seems low, but rituximab and azacytidine seem promising.

• Authors: Arsene Mekinian, Guillaume Dervin, Nathanael Lapidus, Jean-Emmanuel Kahn, Louis Terriou, Eric Liozon, Eric Grignano, Jean-Charles Piette, Odile Beyne Rauzy, Vincent Grobost, Pascal Godmer, Jerome Gillard, Julien Rossignol, David Launay, Achille Aouba, Thierry Cardon, Laurence Bouillet, Jonathan Broner, Julien Vinit, Lionel Ades, Fabrice Carrat, Clementine Salvado, Eric Toussirot, Mathilde Versini, Nathalie Costedoat-Chalumeau, Jean Baptiste Fraison, Philippe Guilpain, Pierre Fenaux, Olivier Fain, GFM, SNFMI, CRI and MINHEMON
• Journal: Autoimmunity reviews (Autoimmun Rev) Vol. 16 Issue 9 Pg. 903-910 (Sep 2017) ISSN: 1873-0183 [Electronic] Netherlands
• PMID: 28705782 (Publication Type: Journal Article, Multicenter Study)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• Biological Products
• Immunologic Factors
• Rituximab
• tocilizumab

Topics

• Aged
• Antibodies, Monoclonal, Humanized (pharmacology, therapeutic use)
• Antirheumatic Agents (pharmacology, therapeutic use)
• Arthritis, Rheumatoid (drug therapy, mortality)
• Biological Products (pharmacology, therapeutic use)
• Disease-Free Survival
• Drug Therapy, Combination
• Female
• France
• Humans
• Immunologic Factors (therapeutic use)
• Male
• Middle Aged
• Myelodysplastic Syndromes (drug therapy, mortality)
• Polychondritis, Relapsing (drug therapy, mortality)
• Retrospective Studies
• Rituximab (pharmacology, therapeutic use)
• Treatment Outcome