ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2333

Adjudication of Infections from the Pharmacovigilance in Juvenile Idiopathic Arthritis Patients (PHARMACHILD) Treated with Biologic Agents and/or Methotrexate with a Focus on Opportunistic Infections

Joost Swart1, Gabriella Giancane1,2, Elio Castagnola1, Andreas Groll1, Gerd Horneff1, Hans-Iko Huppertz1, Daniel J Lovell3, Tom Wolfs1, Michaël Hofer1, Ekaterina Alexeeva1, Violeta Vladislava Panaviene1, Susan Nielsen1, Jordi Anton1, Florence Uettwiller1, Valda Stanevicha1, Maria Trachana1, Fabrizio De Benedetti1, Constantin Ailioaie1, Elena Tsitsami1, Sylvia S.M. Kamphuis1, Troels Herlin1, Pavla Dolezalová1, Gordana Susic1, Berit Flato1, Flavio Sztajnbok1, Elena Fueri4, Francesca Bovis5, Francesca Bagnasco1, Angela Pistorio1, Alberto Martini6, Nico Wulffraat7 and Nicolino Ruperto6, 1Istituto Giannina Gaslini - Pediatria II, Reumatologia - PRINTO, Genoa, Italy, 2Pediatria II, Reumatologia - PRINTO, Istituto Giannina Gaslini - Pediatria II, Reumatologia - PRINTO, Genova, Italy, 3Rheumatology, PRCSG - Cincinnati Children's Hospital Medical Center, Cinncinnati, OH, 4Istituto Giannina Gaslini - Pediatria II, Reumatologia - PRINTO, Genova, Italy, 5Università degli Studi di Genova, Genoa, Italy, 6Istituto Giannina Gaslini, Genoa, Italy, 7Pediatric rheumatology, Wilhelmina Children's Hospital/ UMC Utrecht, Utrecht, Netherlands

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: , , ,

Session Information

Date: Tuesday, November 7, 2017

Title: Pediatric Rheumatology – Pathogenesis and Genetics Poster

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Pharmachild is a pharmacovigilance registry on children with JIA treated mainly with biologics ± methotrexate (MTX). Little evidence exists in literature about the role of JIA or its immunosuppressive therapy in determining infections, especially caused by opportunistic pathogens.

Methods:

To provide an update on opportunistic infections (OI) revised by an independent Safety Adjudication Committee (SAC) (3 pediatric rheumatologists and 2 pediatric infectious disease specialists).

Methods: The participating centres were asked to report all infections encountered by their JIA patients. PRINTO and the medical monitor (MM) classified events based on MedDRA dictionary. Moderate/serious/severe/very severe infections were then revised blindly by the SAC, who were asked to answer 6 questions. The events with consensus of at least 3/5 experts on the first 3 questions (‘Is this an infection?’, ‘Is it common?’, ’Is it opportunistic?’) were retained for the analysis. With referral to the recommendations by Withrop et al.1, for the first time a list of opportunistic infections in children with JIA on immunosuppressive therapy was elaborated and approved by consensus, through three Delphi steps.

Results: A total of 772 safety events related to 634 patients were submitted to the Safety Adjudication Committee. 689 (89.2%) events received consensus among the experts on the 3 questions and, of these, 682 (99.0%) were considered as infections, corresponding to 53 High Level Term (HLT) including 153 different Preferred Terms (PT), according to MedDRA dictionary. Among the 682 infections, 603 (88.4%) were defined by the experts as common and 119 (17.4%) as opportunistic. For 92 (60%) of the 153 PT, the MM and SAC used the same PT, while the remaining 40% was adjudicated by a third examiner, who analyzed again the case reports and assigned the PT which was the most appropriate taking into account the experts’ opinion. A final number of 52 HLT emerged and, among them, herpes viral infections, tract respiratory infections and EBV were the most frequent (Table1). Analyzing the infections by PT, 151 different PT resulted. Of them, the experts adjudicated: 22 as OI, 117 as not OI, 8 discordant and 4 not evaluable. Comparing the experts’ adjudication with the approved list of OI by PT, there was full agreement for the 22 PT classified as OI, while 26/117 (22.2%) PT resulted in the list, but were not classified as OI by the experts.

Conclusion: Our preliminary analysis showed a significant number of opportunistic infections in JIA patients on immunosuppressive therapy, which was mostly confirmed in the list of opportunistic infections approved by the experts. Further analysis on the correlation with medications is ongoing.

References: 1. Winthrop et al. Ann Rheum Dis. 2015;74:2107-16.

Table1. The most frequent HLT for the 682 infections with agreement of at least 3/5 experts on the first 3 questions. (N: number of infections)

HLT

N

%

Herpes viral infections

265

38.9

Lower respiratory tract and lung infections

49

7.2

Upper respiratory tract infections

44

6.5

Epstein-Barr viral infections

38

5.6

Abdominal and gastrointestinal infections

32

4.7

Tuberculous infections

29

4.3

Bacterial infections NEC

27

4

Infections NEC

19

2.8

Ear infections

18

2.6

Candida infections

17

2.5

Influenza viral infections

14

2.1

Streptococcal infections

14

2.1

Salmonella infections

9

1.3

Urinary tract infections

9

1.3

Cytomegaloviral infections

8

1.2

Molluscum contagiosum viral infections

7

1

Papilloma viral infections

7

1

Sepsis, bacteraemia, viraemia and fungaemia NEC

7

1

Campylobacter infections

5

0.7

Staphylococcal infections

5

0.7

Viral infections NEC

5

0.7

Escherichia infections

4

0.6

Pneumocystis infections

4

0.6

Skin structures and soft tissue infections

4

0.6

Disclosure: J. Swart, None; G. Giancane, None; E. Castagnola, None; A. Groll, None; G. Horneff, AbbVie, Pfizer, Novartis, and Roche, 2,AbbVie, Novartis, Sobi, Pfizer, and Roche, 9; H. I. Huppertz, None; D. J. Lovell, AbbVie Inc., AstraZeneca, Centocor, Bristol-Myers Squibb, Pfizer, Regeneron, Hoffman La-Roche, Novartis, UBC, Xoma, and Genentech, 5,Wyeth Pharmaceuticals, 8,Amgen and Forest Research, 9; T. Wolfs, None; M. Hofer, Novartis and AbbVie, 5; E. Alexeeva, None; V. V. Panaviene, None; S. Nielsen, None; J. Anton, Roche Pharmaceuticals, 2; F. Uettwiller, None; V. Stanevicha, None; M. Trachana, None; F. De Benedetti, Novartis, Roche, Pfizer, SOBI, AbbVie, Novimmune, BMS, Sanofi, 2; C. Ailioaie, None; E. Tsitsami, None; S. S. M. Kamphuis, None; T. Herlin, None; P. Dolezalová, None; G. Susic, Pfizer Inc, 2; B. Flato, None; F. Sztajnbok, None; E. Fueri, None; F. Bovis, None; F. Bagnasco, None; A. Pistorio, None; A. Martini, GASLINI Hospital, 3,Astellas, AstraZeneca, Bristol-Myers Squibb, Italfarmaco, and MedImmune, 8,AbbVie Inc., AstraZeneca, Bristol-Myers Squibb, Janssen Biologics B.V., Eli Lilly and Co., “Francesco Angelini”, GlaxoSmithKline, Italfarmaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, and Wyeth Pharmaceuticals, 2; N. Wulffraat, None; N. Ruperto, BMS, Hoffman-La Roche, Janssen, Novartis, Pfizer and Sobi, 2,Abbvie, Ablynx, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol Myers Squibb, Eli-Lilly, EMD Serono, Gilead Sciences, Janssen, Medimmune, Novartis, Pfizer, Rpharm, Roche, Sanofi., 5,Abbvie, Ablynx, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol Myers Squibb, Eli-Lilly, EMD Serono, Gilead Sciences, Janssen, Medimmune, Novartis, Pfizer, Rpharm, Roche, Sanofi., 8.

To cite this abstract in AMA style:

Swart J, Giancane G, 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, De Benedetti F, Ailioaie C, Tsitsami E, Kamphuis SSM, Herlin T, Dolezalová P, Susic G, Flato B, Sztajnbok F, Fueri E, Bovis F, Bagnasco F, Pistorio A, Martini A, Wulffraat N, Ruperto N. Adjudication of Infections from the Pharmacovigilance in Juvenile Idiopathic Arthritis Patients (PHARMACHILD) Treated with Biologic Agents and/or Methotrexate with a Focus on Opportunistic Infections [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/adjudication-of-infections-from-the-pharmacovigilance-in-juvenile-idiopathic-arthritis-patients-pharmachild-treated-with-biologic-agents-andor-methotrexate-with-a-focus-on-opportunistic-infections/. Accessed .

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