ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 3116

Risk of Infections in Juvenile Idiopathic Arthritis Patients Treated with Biologic Agentsand/or Methotrexate: Results from Pharmachild Registry

Gabriella Giancane1, Joost Swart2, Francesca Bovis2, Elio Castagnola2, Andreas Groll2, Gerd Horneff2, Hans-Iko Huppertz2, Daniel J. Lovell2, Tom Wolfs2, Michaël Hofer2, Ekaterina Alexeeva2, Violeta Vladislava Panaviene2, Susan Nielsen2, Jordi Anton2, Florence Uettwiller2, Valda Stanevicha2, Maria Trachana2, Denise Pires Marafon3, Constantin Ailioaie2, Elena Tsitsami2, Sylvia S.M. Kamphuis2, Troels Herlin2, Pavla Dolezalová3, Gordana Susic2, Berit Flato2, Flavio Sztajnbok2, Angela Pistorio1, Alberto Martini2, Nico Wulffraat2 and Nicolino Ruperto2, 1Pediatria II, Reumatologia, PRINTO, Istituto Giannina Gaslini, Genoa, Italy, 2Istituto Giannina Gaslini, Genoa, Italy, 3Istituto Giannina Gaslini, genoa, Italy

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: , ,

Session Information

Date: Wednesday, November 16, 2016

Session Title: ACR/ARHP Combined Abstract Session: Pediatric Rheumatology

Session Type: ACR Concurrent Abstract Session

Session Time: 9:00AM-10:30AM

Background/Purpose: Pharmachild is an international registry involving over 100 the Paediatric Rheumatology INternational Trials Organisation (PRINTO)/ the Paediatric Rheumatology European Society (PRES) centres in 38 countries. The registry was set up to evaluate long term safety and efficacy of treatments in children with JIA. The purpose of the study was to evaluate the occurrence of infections in JIA children and their relationship with biologics ± methotrexate (MTX) and other immunosuppressants.

Methods: Retrospective and prospective evaluation of moderate to very severe and serious infections. We investigated, by means of bivariate and multivariate modeling, the relationship between infections and the drugs used in the 6 month-history prior to the infection and, for patients without infections, in the 6 months prior to the last follow-up visit. The patients receiving only NSAIDs or intra-articular steroid injections were used as a reference.

Results: We analyzed 6969 patients, for a total of 689 (10%) patients with infections. Patients were systemic 639 (9%), polyarticular course 4587 (66%) and persistent oligoarthritis 1473 (25%). Patients with infections were treated in the previous 6 months primarily with MTX (82%), corticosteroids (32%), anti-TNF (52%), anti IL-1/IL-6 (8%), rituximab (2%) or other biologics (2%).Earlier age at diagnosis (≤7.7 years), ANA positivity, and systemic JIA category significantly increased the risk for infection (OR 2.3, 1.7 and 2.2, respectively). The analysis of the impact of the single immunosuppressive drugs showed that the risk for infection is increased by corticosteroids (OR 3.7), MTX (OR 2.8), cyclosporine (OR 5.3) and thalidomide (OR 13.7, 3/5 patients with infections). The same results were observed for biologics, in particular rituximab (OR 16.3, 14/22 patients with infections), IL-1 inhibitors as anakinra (OR 3.3) and, among TNF-α inhibitors, infliximab (OR 1.6). Conversely, abatacept resulted protective (OR 0.4). The multivariate analysis (table) revealed that the addition of steroids to both MTX and biologics (groups MTX + steroids and MTX + steroids + biologics) increased the risk of infections more significantly (OR 11.9 and 10.5, respectively) than only MTX (5.1) or MTX+Biologics (OR 3.7). A great increase in the risk for infection was associated with rituximab ± steroids ± DMARDs (OR 112, 95% CI 11-1000). The multivariate results were confirmed by removing rituximab patients from the model. Table. Risk factors for infections in JIA patients by multivariate analysis. (REF: reference item)

 

Patients with infections

Multivariate analysis

N=689

OR (95%CI)

Drug Therapy    
Only NSAIDs and Intraarticular Steroids (REF)
Rituximab ± Steroids ± DMARDS

12/16 (75%)

111.8 (10.7-999.9)

MTX+Biologics+Steroids

95/422 (23%)

10.5 (6.5-17.0)

MTX+Steroids

47/207 (23%)

11.9 (7.0-20.2)

Other combinations

102/689 (15%)

7.6 (4.8-12.0)

Only MTX

157/1418 (11%)

5.1 (3.3-7.9)

MTX+Biologics

181/2055 (9%)

3.7 (2.4-5.8)

Only Biologics

71/1077 (7%)

2.7 (1.7-4.3)

Diagnosis (Oligo Persistent arthritis as REF)
Other JIA categories with polyarticular course

451/4587 (10%)

1.3 (1.1-1.6)

Systemic arthritis 

100/639 (16%)

1.7 (1.3-2.3)

Age at JIA diagnosis (cut-off ≤7.7)

523/4136 (13%)

2.3 (1.9-2.7)

ANA (2 positive >1:160)

219/1595 (14%)

1.6 (1.3-1.9)

Conclusion: Pharmachild showed that MTX and biologics increase the risk of infection in JIA patients. This risk is significantly enhanced by the addition of steroids to immunosuppressive therapy. We recommend monitoring for infections in JIA patients on immunosuppressive therapy.  

Disclosure: G. Giancane, None; J. Swart, None; F. Bovis, None; E. Castagnola, Pfizer, Astellas Pharma, Basilea Pharmaceutica, 8; A. Groll, None; G. Horneff, None; H. I. Huppertz, None; D. J. Lovell, None; T. Wolfs, None; M. Hofer, None; E. Alexeeva, None; V. V. Panaviene, None; S. Nielsen, None; J. Anton, None; F. Uettwiller, None; V. Stanevicha, None; M. Trachana, None; D. Pires Marafon, None; C. Ailioaie, None; E. Tsitsami, None; S. S. M. Kamphuis, None; T. Herlin, None; P. Dolezalová, AbbVie, Roche, Medac, Novartis, , Pfizer, Consultant: Roche, 2,Pfizer, Novartis, Medac, 8; G. Susic, None; B. Flato, None; F. Sztajnbok, None; A. Pistorio, None; A. Martini, BMS, GlaxoSmithKline (GSK), Hoffman-La Roche, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Abbott, Francesco Angelini S.P.A., Sobi, Merck Serono, 2,Abbvie, Boehringer, Celgene, CrescendoBio, Janssen, Meddimune, Novartis, NovoNordisk, Pfizer, Sanofi Aventis, Vertex, Servier., 8; N. Wulffraat, None; N. Ruperto, BMS, GlaxoSmithKline (GSK), Hoffman-La Roche, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Abbott, Francesco Angelini S.P.A., Sobi, Merck Serono., 2,AbbVie, Amgen, Biogenidec, Alter, AstraZeneca, Baxalta Biosimilars, Biogenidec, Boehringer, BMS, Celgene, CrescendoBio, EMD Serono, Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda,, 8.

To cite this abstract in AMA style:

Giancane G, Swart J, Bovis F, Castagnola E, Groll A, Horneff G, Huppertz HI, Lovell DJ, Wolfs T, Hofer M, Alexeeva E, Panaviene VV, Nielsen S, Anton J, Uettwiller F, Stanevicha V, Trachana M, Pires Marafon D, Ailioaie C, Tsitsami E, Kamphuis SSM, Herlin T, Dolezalová P, Susic G, Flato B, Sztajnbok F, Pistorio A, Martini A, Wulffraat N, Ruperto N. Risk of Infections in Juvenile Idiopathic Arthritis Patients Treated with Biologic Agentsand/or Methotrexate: Results from Pharmachild Registry [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/risk-of-infections-in-juvenile-idiopathic-arthritis-patients-treated-with-biologic-agentsandor-methotrexate-results-from-pharmachild-registry/. Accessed January 16, 2021.

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