Complications of Varicella Zona Virus Infections Are More Frequent in Patients Treated with Biologic Drugs When Combined with Steroids

Jacques Morel¹, Florence Tubach^2,3, Yannick Allanore⁴, Daniel Wendling⁵, Celine Cozic⁶, Emmanuelle Dernis Labous⁷, Eric Legangneux⁸, Thao Pham⁹, Sophie Odoit¹⁰, Isabelle Roitg¹¹, Isabelle Koné-Paut¹², Pierre Quartier¹³, Jean Sibilia¹⁴ and Severine Guillaume Czitrom¹⁵, ¹Rheumatology, Hopital Lapeyronie, Montpellier, France, ²Département d'Epidémiologie Biostatistique et Recherche Clinique, APHP, Hôpital Bichat, Paris, France, ³INSERM, Universite Paris Diderot, Paris, France, ⁴Paris Descartes University, Rheumatology A Department and INSERM U1016, Cochin Hospital, Paris, France, ⁵Service de Rhumatologie, CHU J Minjoz, Besancon, France, ⁶Rheumatology, CHD la Roche sur Yon, La Roche Sur Yon, France, ⁷Rhumatologie, Ch Du Mans, Le Mans, France, ⁸Rheumatology, Centre Hospitalier Public du Cotentin, 50100, France, ⁹Rheumatology Department, Sainte Marguerite Hospital, Marseille, France, ¹⁰Dermatology, CHU de la Réunion, Saint Denis, France, ¹¹Hopital De Perpignan, Perpignan, France, ¹²Pediatrics Rheumatology, CHU Bicêtre, Le Kremlin Bicêtre, France, ¹³Pediatric Rheumatology, IMAGINE Institute, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Université Paris-Descartes, Paris, France, ¹⁴Division of Rheumatology, University Hospital of Strasbourg, Strasbourg, France, ¹⁵Ch De Bicetre, Le Kremlin Bicetre Cedex, France

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Biologic drugs, complications, Infection, steroids and viruses

Session Information

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy: Safety of Biologics and Small Molecules in Rheumatoid Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose

To assess varicella zona virus (VZV) infection features under biological drugs.

Methods

A call for observations was sent from april 2013 to april 2014 by email through the Club Rheumatism et Inflammation website to collect varicella zona virus (VZV) infections in adults and children under biologic DMARDs (bDMARDs). Cases collected between february 1st 2004 and january 31th 2007, by the french observational study RATIO were added. Khi-two or Fisher tests were used for qualitative variables when appropriate.

Results

103 VZV infections were collected in 76 adults and 27 children receiving anti-TNF (71), anti-IL-1 (10), rituximab (10), tocilizumab (8) and abatacept (4) for rheumatoid arthritis (46), spondyloarthritis (15), juvenile induced idiopathic arthritis excluding Still’s diseases (11), Still’s disease (11), Crohn’s disease (8), psoriasis or psoriatic arthritic (3), connectivite connective tissue disease (2) and other chronic inflammatory diseases (6). Adult patients were mainly women (72.4%), 56% aged 19-60 years old and the others were over 60. At the time of infection, associated to bDMARDs were NSAIDs in 5 patients were on NSAID, steroids in 43 on steroids, conventional synthetic (cs) DMARDs in 54 on conventional synthetic (cs) DMARDs and 9 immunosuppressive drugs in 9. VZV infections occurred late after drug onset (> 6 months for 97.2% of patients with steroids, 70.2% for bDMARDs and after 3 years for cs DMARDs for 70.4%. 27 children aged less than 18, mainly girls (74.1%) were treated with methotrexate (15) or immune-suppressive drugs (2) combined with NSAIDs for 10 patients in addition to bDMARDs. Most children were on steroids (11), or bDMARDs (16) for at least 6 months when VZV infection occurred. None of the patients had been vaccinated against VZV. Zoster was more frequently observed in adults (68/76 adults), whereas varicella was most often reported in children (18/27). For varicella, 4 complications were reported in adults (2 skin and 2 disseminated) and 2 in children (1 ophthalmic and 1 disseminated). Complications were more frequent for zoster: 40 in adults (28 skin, 6 neurological, 6 ophthalmic) and 2 in children (1 neurological and 1 ophthalmic). Complications were significantly higher in patients on steroids (p=0.02 vs non steroid group) and tend to be more elevated in anti-TNF group (p=0.055 vs non TNF inhibitor bDMARDs). None received IV immunoglobulin. 90 patients (71 adults and 19 children) were treated with an anti-herpes virus (HSV) drug usually prescribed oral for 1 to 2 weeks and intravenously in 28 patients. NSAIDs were pursued in 11% of the children and 83% of the adults. bDMARDs were at least transiently interrupted in 63 patients (62%) and csDMARDs were stopped for 17 patients. Outcome was favourable for 98 patients with no death.

Conclusion

In this retrospective study, VZV infections were mainly varicella in children and zoster in adults. Outcome was favourable in most cases even when bDMARDs or NSAIDs were pursued and remarkably, even when no specific treatment of VZV infection was applied. Under bDMARDS, complications of VZV infections occurred more frequently in patients treated with steroids.

Disclosure:

J. Morel,

Roche Pharmaceuticals,

Pfizer Inc,

Bristol-Myers Squibb,

Union Chimique Belge,

Merck Pharmaceuticals,

Abbott Laboratories,

F. Tubach,
None;

Y. Allanore,
None;

D. Wendling,
None;

C. Cozic,
None;

E. Dernis Labous,
None;

E. Legangneux,
None;

T. Pham,
None;

S. Odoit,
None;

I. Roitg,
None;

I. Koné-Paut,
None;

P. Quartier,

AbbVie, Novartis, Pfizer, BMS, Chugai-Roche, Medimmune, Servier, and Swedish Orphan Biovitrum,

J. Sibilia,
None;

S. Guillaume Czitrom,
None.

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