Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: analysis by the Pharmachild Safety Adjudication Committee

Gabriella Giancane, Joost F Swart, Elio Castagnola, Andreas H Groll, Gerd Horneff, Hans-Iko Huppertz, Daniel J Lovell, Tom Wolfs, Troels Herlin, Pavla Dolezalova, Helga Sanner, Gordana Susic, Flavio Sztajnbok, Despoina Maritsi, Tamas Constantin, Veronika Vargova, Sujata Sawhney, Marite Rygg, Sheila K Oliveira, Marco Cattalini, Francesca Bovis, Francesca Bagnasco, Angela Pistorio, Alberto Martini, Nico Wulffraat, Nicolino Ruperto, Paediatric Rheumatology International Trials Organisation (PRINTO), Ruben Cuttica, Stella Maris Garay, Jurgen Brunner, Wolfgang Emminger, Simone Appenzeller, Claudio Len, Claudia Saad Magalhaes, Albena Telcharova-Mihaylovska, Miroslav Harjacek, Marija Jelusic, Anne Estmann, Susan Nielsen, Cristina Herrera Mora, Elisabeth Gervais, Isabelle Koné-Paut, Pierre Quartier, Ivan Foeldvari, Gerd Horneff, Thomas Lutz, Kirsten Minden, Nikolay Tzaribachev, Maria Trachana, Elena Tsitsami, Olga Vougiouka, Ilonka Orban, Liora Harel, Philip Hashkes, Yosef Uziel, Rolando Cimaz, Adele Civino, Rita Consolini, Gianfranco D'Angelo, Fabrizio De Benedetti, Giovanni Filocamo, Elena Fueri, Romina Gallizzi, Maria Cristina Maggio, Maria Greca Magnolia, Angela Miniaci, Davide Montin, Alma Nunzia Olivieri, Serena Pastore, Donato Rigante, Francesco Zulian, Ingrida Rumba-Rozenfelde, Valda Stanevicha, Violeta Panaviene, Ana Luisa Rodriguez Lozano, Nadina Rubio-Perez, Gabriel Vega Cornejo, Esther Hoppenreijs, Sylvia Kamphuis, Berit Flato, Ellen Berit Nordal, Reem Abdwani, Tatiana Miraval, Maria Eliana Paz Gastanaga, Elzbieta Smolewska, Constantin Ailioaie, Alexis-Virgil Cochino, Matilda Laday, Calin Lazar, Ekaterina Alexeeva, Vyacheslav Chasnyk, Vladimir Keltsev, Wafaa Mohammed Saad Suwairi, Gordana Vijatov-Djuric, Jelena Vojinovic, Thaschawee Arkachaisri, Elena Koskova, Tadej Avcin, Mahmood Ally, Christa Janse Van Rensburg, Ingrid Louw, Jordi Anton Lopez, Alina Lucica Boteanu, Inmaculada Calvo Penades, Jaime De Inocencio, Pablo Mesa-Del-Castillo, Estefania Moreno, Agustin Remesal, Michael Hofer, Faysal Gok, Seza Ozen, Athimalaipet Ramanan, Chiara Pallotti, Luca Villa, Gabriella Giancane, Joost F Swart, Elio Castagnola, Andreas H Groll, Gerd Horneff, Hans-Iko Huppertz, Daniel J Lovell, Tom Wolfs, Troels Herlin, Pavla Dolezalova, Helga Sanner, Gordana Susic, Flavio Sztajnbok, Despoina Maritsi, Tamas Constantin, Veronika Vargova, Sujata Sawhney, Marite Rygg, Sheila K Oliveira, Marco Cattalini, Francesca Bovis, Francesca Bagnasco, Angela Pistorio, Alberto Martini, Nico Wulffraat, Nicolino Ruperto, Paediatric Rheumatology International Trials Organisation (PRINTO), Ruben Cuttica, Stella Maris Garay, Jurgen Brunner, Wolfgang Emminger, Simone Appenzeller, Claudio Len, Claudia Saad Magalhaes, Albena Telcharova-Mihaylovska, Miroslav Harjacek, Marija Jelusic, Anne Estmann, Susan Nielsen, Cristina Herrera Mora, Elisabeth Gervais, Isabelle Koné-Paut, Pierre Quartier, Ivan Foeldvari, Gerd Horneff, Thomas Lutz, Kirsten Minden, Nikolay Tzaribachev, Maria Trachana, Elena Tsitsami, Olga Vougiouka, Ilonka Orban, Liora Harel, Philip Hashkes, Yosef Uziel, Rolando Cimaz, Adele Civino, Rita Consolini, Gianfranco D'Angelo, Fabrizio De Benedetti, Giovanni Filocamo, Elena Fueri, Romina Gallizzi, Maria Cristina Maggio, Maria Greca Magnolia, Angela Miniaci, Davide Montin, Alma Nunzia Olivieri, Serena Pastore, Donato Rigante, Francesco Zulian, Ingrida Rumba-Rozenfelde, Valda Stanevicha, Violeta Panaviene, Ana Luisa Rodriguez Lozano, Nadina Rubio-Perez, Gabriel Vega Cornejo, Esther Hoppenreijs, Sylvia Kamphuis, Berit Flato, Ellen Berit Nordal, Reem Abdwani, Tatiana Miraval, Maria Eliana Paz Gastanaga, Elzbieta Smolewska, Constantin Ailioaie, Alexis-Virgil Cochino, Matilda Laday, Calin Lazar, Ekaterina Alexeeva, Vyacheslav Chasnyk, Vladimir Keltsev, Wafaa Mohammed Saad Suwairi, Gordana Vijatov-Djuric, Jelena Vojinovic, Thaschawee Arkachaisri, Elena Koskova, Tadej Avcin, Mahmood Ally, Christa Janse Van Rensburg, Ingrid Louw, Jordi Anton Lopez, Alina Lucica Boteanu, Inmaculada Calvo Penades, Jaime De Inocencio, Pablo Mesa-Del-Castillo, Estefania Moreno, Agustin Remesal, Michael Hofer, Faysal Gok, Seza Ozen, Athimalaipet Ramanan, Chiara Pallotti, Luca Villa

Abstract

Background: To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC).

Methods: The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI.

Results: A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI.

Conclusions: We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies.

Trial registration: Clinicaltrials.gov NCT01399281; ENCePP seal: awarded on 25 November 2011.

Keywords: Biologics; Immunosuppressive therapy; Infections; Juvenile idiopathic arthritis; Opportunistic.

Conflict of interest statement

GG declares that she has no competing interests.

JFS has received sponsorship for a meeting by Sobi (< $10,000 USD).

EC declares that he has no competing interests.

AHG has received research grants from Gilead, Merck, Sharp & Dohme, and Pfizer; is or has been a consultant to Amplyx, Astellas, Basilea, F2G, Gilead, Merck, Sharp & Dohme, and Pfizer; and served at the speakers’ bureau of Astellas, Basilea, Gilead, Merck, Sharp & Dohme, Pfizer, and Schering-Plough. All of the above is < 10.000 per entity.

GH has received consultancies, speaking fees, and honoraria from Abbvie, Chugai, Pfizer, Novartis, Roche, and Sanofi (< $10,000 USD each).

HIH declares that he has no competing interests.

DJL has served on speaker bureaus for Genentech and Bristol-Meyers Squibb and served on a data and safety monitoring boards for Forest Research and the NIH-NIAMS; the Cincinnati Children’s Hospital Medical Center has received consulting fees for the work of Dr. Lovell from AbbVie, AstraZeneca, Bristol-Myers Squibb, Centocor, Genentech, Hoffman-La Roche, Lilly, Janssen, Novartis, Pfizer, Regeneron, R-Pharm and UBC. Each activity is less than $10,000.

TW declares that he has no competing interests.

TH declares that he has no competing interests.

PD has received speaker’s fees or consultancies or travel grants (all < 10,000 USD) from Medac, Novartis, Abbvie, Roche, SOBI, and Lilly.

HS declares that she has no competing interests.

GS has received honoraria as a sub-investigator in a Pfizer trial (> 10,000 USD).

FS declares that he has no competing interests.

DM declares that she has no competing interests.

TC has received consultancies, speaking fees, and honoraria from Roche and Abbvie < $10,000.

VV has received consultancies, speaking fees, and honoraria from Pfizer, Abbvie, and Sobi (< $10,000).

SS declares that she has no competing interests.

MR declares that she has no competing interests.

SKO has received teaching honoraria from Pfizer (< $10,000).

MC declares that he has no competing interests.

FBo received teaching honoraria from Novartis (< $10,000) and consulting fees from Biogen (< $10,000).

FBa declares that she has no competing interests.

AP declares that she has no competing interests.

AM: starting from 1 March 2016 to December 2018 Prof. Alberto Martini did not have any conflict of interest to declare since he was the Scientific Director of IRCCS Istituto Gaslini and this role did not allow him to render private consultancies resulting in personal income. He performed consultancy activities on behalf of the Gaslini Institute for the following companies: Abbvie, Biogen, Boehringer, Bristol-Myers and Squibb, EMD Serono, Janssen, Novartis, Pfizer, and R-Pharm. The money received for these activities was directly transferred to the Gaslini Institute’s bank account. Since January 2019, Prof. Alberto Martini is no longer the Scientific Director of IRCCS Istituto Gaslini; therefore, he can perform private consultancy services. Currently, he has active consultancy agreements with Janssen, Novartis, and Pfizer (< 10.000 USD each).

NW has received an institutional research grant from AbbVie (> 10,000 USD) for an e-health project. Consultancies: BMS (< 10,000 USD) on e-health developments.

NR has received honoraria for consultancies or speaker bureaus (< 10.000 USD each) from the following pharmaceutical companies in the past 3 years: Ablynx, AbbVie, Astrazeneca-Medimmune, Biogen, Boehringer, Bristol-Myers and Squibb, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, SanofiServier, Sinergie, Sobi, and Takeda. The Gaslini Hospital, where NR works as full-time public employee, has received contributions (> 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, and Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties.

Figures

Fig. 1
Fig. 1
Flowchart of the Pharmachild population with infectious events

References

    1. Lovell DJ, Giannini EH, Reiff A, Cawkwell D, Silverman ED, Nocton JJ, et al. Etanercept in children with polyarticular juvenile rheumatoid arthritis. N Engl J Med. 2000;342(11):763–769. doi: 10.1056/NEJM200003163421103.
    1. Lovell DJ, Reiff A, Ilowite NT, Wallace CA, Chon Y, Lin SL, et al. Safety and efficacy of up to eight years of continuous etanercept therapy in patients with juvenile rheumatoid arthritis. Arthritis Rheum. 2008;58(5):1496–1504. doi: 10.1002/art.23427.
    1. Giannini EH, Ilowite NT, Lovell DJ, Wallace CA, Rabinovich CE, Reiff A, et al. Effects of long-term etanercept treatment on growth in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum. 2010;62(11):3259–3264. doi: 10.1002/art.27682.
    1. Horneff G, Burgos-Vargas R, Constantin T, Foeldvari I, Vojinovic J, Chasnyk VG, et al. Efficacy and safety of open-label etanercept on extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis and psoriatic arthritis: part 1 (week 12) of the CLIPPER study. Ann Rheum Dis. 2014;73(6):1114–1122. doi: 10.1136/annrheumdis-2012-203046.
    1. Constantin T, Foeldvari I, Vojinovic J, Horneff G, Burgos-Vargas R, Nikishina I, et al. Two-year efficacy and safety of etanercept in pediatric patients with extended oligoarthritis, enthesitis-related arthritis, or psoriatic arthritis. J Rheumatol. 2016;43(4):816–824. doi: 10.3899/jrheum.150430.
    1. Verazza S, Davi S, Consolaro A, Bovis F, Insalaco A, Magni-Manzoni S, et al. Disease status, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept. Pediatr Rheumatol Online J. 2016;14(1):68. doi: 10.1186/s12969-016-0126-0.
    1. Ruperto N, Lovell DJ, Cuttica R, Woo P, Meiorin S, Wouters C, et al. Long-term efficacy and safety of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis: findings from an open-label treatment extension. Ann Rheum Dis. 2010;69(4):718–722. doi: 10.1136/ard.2009.100354.
    1. Lovell DJ, Ruperto N, Goodman S, Reiff A, Jung L, Jarosova K, et al. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med. 2008;359(8):810–820. doi: 10.1056/NEJMoa0706290.
    1. Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-Perez N, Silva CA, et al. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial. Lancet. 2008;372(9636):383–391. doi: 10.1016/S0140-6736(08)60998-8.
    1. Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-Perez N, Silva CA, et al. Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis. Arthritis Rheum. 2010;62(6):1792–1802. doi: 10.1002/art.27431.
    1. Lovell DJ, Ruperto N, Mouy R, Paz E, Rubio-Perez N, Silva CA, et al. Long-term safety, efficacy, and quality of life in patients with juvenile idiopathic arthritis treated with intravenous abatacept for up to seven years. Arthritis Rheumatol. 2015;67(10):2759–2770. doi: 10.1002/art.39234.
    1. De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, Calvo I, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367(25):2385–2395. doi: 10.1056/NEJMoa1112802.
    1. Brunner HI, Ruperto N, Zuber Z, Keane C, Harari O, Kenwright A, et al. Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial. Ann Rheum Dis. 2015;74(6):1110–1117. doi: 10.1136/annrheumdis-2014-205351.
    1. Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat N, Horneff G, et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367(25):2396–2406. doi: 10.1056/NEJMoa1205099.
    1. Brunner HI, Ruperto N, Tzaribachev N, Horneff G, Chasnyk VG, Panaviene V, et al. Subcutaneous golimumab for children with active polyarticular-course juvenile idiopathic arthritis: results of a multicentre, double-blind, randomised-withdrawal trial. Ann Rheum Dis 2017 May 15;[Epub ahead of print].
    1. FDA . FDA: cancer warnings required for TNF blockers. 2009.
    1. Ruperto N, Vesely R, Saint-Raymond A, Martini A. Impact of the European paediatric legislation in paediatric rheumatology: past, present and future. Ann Rheum Dis. 2013;72(12):1893–1896. doi: 10.1136/annrheumdis-2013-204168.
    1. Magnusson B, Board of Registry The Swedish paediatric JIA-registry. Pediatric Rheumatol. 2014;12(S1):P5. doi: 10.1186/1546-0096-12-S1-P5.
    1. McErlane F, Foster HE, Davies R, Lunt M, Watson K, Symmons DPM, et al. Biologic treatment response among adults with juvenile idiopathic arthritis: results from the British Society for Rheumatology Biologics Register. Rheumatology. 2013;52:1905–1913. doi: 10.1093/rheumatology/ket248.
    1. Mourao AF, Santos M, Melo-Gomes JA. Effectiveness and long-term retention of anti-tumour necrosis factor treatment in juvenile and adult patients with juvenile idiopathic arthritis: data from . Rheumatology (Oxford) 2016;55(4):697–703. doi: 10.1093/rheumatology/kev398.
    1. Horneff G. Biologic-associated infections in pediatric rheumatology. Curr Rheumatol Rep. 2015;17:66. doi: 10.1007/s11926-015-0542-z.
    1. Horneff G, Schulz AC, Klotsche J, Hospach A, Minden K, Foeldvari I, et al. Experience with etanercept, tocilizumab and interleukin-1 inhibitors in systemic onset juvenile idiopathic arthritis patients from the BIKER registry. Arthritis Res Ther. 2017;19(1):256. doi: 10.1186/s13075-017-1462-2.
    1. Becker I, Horneff G. Risk of serious infection in juvenile idiopathic arthritis patients associated with tumor necrosis factor inhibitors and disease activity in the German biologics in pediatric rheumatology registry. Arthritis Care Res (Hoboken) 2017;69(4):552–560. doi: 10.1002/acr.22961.
    1. Horneff G, Foeldvari I, Minden K, Moebius D, Hospach T. Report on malignancies in the German juvenile idiopathic arthritis registry. Rheumatology (Oxford) 2011;50(1):230–236. doi: 10.1093/rheumatology/keq361.
    1. Prince FH, Ferket IS, Kamphuis S, Armbrust W, ten CR, Hoppenreijs EP, et al. Development of a web-based register for the Dutch national study on biologicals in JIA: . Rheumatology (Oxford). 2008;47(9):1413–6.
    1. Prince FH, Twilt M, ten CR VRMA, Armbrust W, Hoppenreijs EP, et al. Long-term follow-up on effectiveness and safety of etanercept in juvenile idiopathic arthritis: the Dutch national register. Ann Rheum Dis. 2009;68(5):635–641. doi: 10.1136/ard.2007.087411.
    1. Otten MH, Prince FH, Armbrust W, ten CR HEP, Twilt M, et al. Factors associated with treatment response to etanercept in juvenile idiopathic arthritis. JAMA. 2011;306(21):2340–2347. doi: 10.1001/jama.2011.1671.
    1. Beukelman T, Ringold S, Davis TE, DeWitt EM, Pelajo CF, Weiss PF, et al. Disease-modifying antirheumatic drug use in the treatment of juvenile idiopathic arthritis: a cross-sectional analysis of the CARRA registry. J Rheumatol. 2012;39(9):1867–1874. doi: 10.3899/jrheum.120110.
    1. Beukelman T, Haynes K, Curtis JR, Xie F, Chen L, Bemrich-Stolz CJ, et al. Rates of malignancy associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum. 2012;64(4):1263–1271. doi: 10.1002/art.34348.
    1. Beukelman T, Xie F, Chen L, Baddley JW, Delzell E, Grijalva CG, et al. Rates of hospitalized bacterial infection associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum. 2012;64(8):2773–2780. doi: 10.1002/art.34458.
    1. Beukelman T, Xie F, Baddley JW, Chen L, Delzell E, Grijalva CG, et al. Brief report: incidence of selected opportunistic infections among children with juvenile idiopathic arthritis. Arthritis Rheum. 2013;65(5):1384–1389. doi: 10.1002/art.37866.
    1. Winthrop KL, Novosad S, Baddley JW, Calabrese L, Chiller T, Polgreen P, et al. Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases: consensus recommendations for infection reporting during clinical trials and postmarketing surveillance. Ann Rheum Dis. 2015;74(12):2107–2116. doi: 10.1136/annrheumdis-2015-207841.
    1. Winthrop KL, Chen L, Fraunfelder FW, Ku JH, Varley CD, Suhler E, et al. Initiation of anti-TNF therapy and the risk of optic neuritis: from the Safety Assessment of Biologic ThERapy (SABER) study. Am J Ophthalmol. 2013;155(1):183–189. doi: 10.1016/j.ajo.2012.06.023.
    1. Abinun M. Risks of serious infections in children treated with biologic response-modifying drugs. Rheumatology. 2018;57(2):1–2.
    1. Calzada-Hernández J, Anton J, Bou-Torrent R, Iglesias-Jiménez E, Ricart-Campos S, Martin de Carpi J, et al. Tuberculosis in pediatric patients treated with anti-TNFá drugs: a cohort study. Pediatric Rheumatology. 2015;13:54. doi: 10.1186/s12969-015-0054-4.
    1. Ringold S, Weiss PF, Beukelman T, DeWitt EM, Ilowite NT, Kimura Y, et al. 2013 update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications. Arthritis Care Res (Hoboken) 2013;65(10):1551–1563. doi: 10.1002/acr.22087.
    1. Hsin YC, Zhuang L, Yeh K, Chang C, Horng J, Huang JL. Risk of tuberculosis in children with juvenile idiopathic arthritis: a nationwide population-based study in Taiwan. PLoS One. 2018;10(6). eCollection.
    1. Ruperto N, Martini A. Networking in paediatrics: the example of the Paediatric Rheumatology International Trials Organisation (PRINTO) Arch Dis Child. 2011;96(6):596–601. doi: 10.1136/adc.2010.188946.
    1. Swart J, Giancane G, Horneff G, Magnusson B, Hofer M, Alexeeva E, et al. Pharmacovigilance in juvenile idiopathic arthritis patients treated with biologic or synthetic drugs: combined data of more than 15,000 patients from Pharmachild and national registries. Arthritis Res Ther. 2018;20(1):285. doi: 10.1186/s13075-018-1780-z.
    1. Groll A, Castagnola E, Cesaro S, Dalle J, Engelhard D, et al. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation. Lancet Oncol. 2014;15:327–340. doi: 10.1016/S1470-2045(14)70017-8.
    1. Mofenson LM, Brady M, Danner S, Dominguez K, Hazra R, Handelsman E, et al. Guidelines for the prevention and treatment of opportunistic infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep. 2009;58(RR-11):1–166.
    1. Maertens J, Cesaro S, Maschmeyer G, Einsele H, Donnelly J, Alanio A, et al. ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother. 2016;71:2397–2404. doi: 10.1093/jac/dkw157.
    1. Naidoo J, Mahomed N, Moodley H. A systemic review of tuberculosis with HIV coinfection in children. Pediatr Radiol. 2017;47:1269–1276. doi: 10.1007/s00247-017-3895-9.
    1. Tragiannidis A, Kyriakidis I, Zundorf I, Groll A. Invasive fungal infections in pediatric patients treated with tumor necrosis alpha (TNF-alpha) inhibitors. Mycoses. 2017;60:222–229. doi: 10.1111/myc.12576.
    1. Davies D, FAAP COID Infectious complications with the use of biologic response modifiers in infants and children. Pediatrics. 2016;138:e11–e21.
    1. Hashkes PJ, Uziel Y, Laxer RM. The safety profile of biologic therapies for juvenile idiopathic arthritis. Nat Rev Rheumatol. 2010;6(10):561–571. doi: 10.1038/nrrheum.2010.142.
    1. Lionetti G, Kimura Y, Schanberg L. Using registries to identify adverse events in rheumatic diseases. Pediatrics. 2013;132(5):1384–1394. doi: 10.1542/peds.2013-0755.
    1. ATS Board of Directors of the american Thoracic Society Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161(4 Pt 2):S221–S247.
    1. Nimmrich S, Horneff G. Incidence of herpes zoster infections in JIA patients. Rheumatol Int. 2015;35:465–470. doi: 10.1007/s00296-014-3197-6.
    1. Nicolai R, Cortis E, Rava L, Bracaglia C, Pardeo M, Insalaco A, et al. Herpes virus infections during treatment with etanercept in juvenile idiopathic arthritis. J Pediatric Infect Dis Soc. 2016;5(1):76–79. doi: 10.1093/jpids/piu078.
    1. Leuvenink R, Aeschlimann F, Baer W, Berthet G, Cannizzaro E, Hofer M, et al. Clinical course and therapeutic approach to varicella zoster virus infection in children with rheumatic autoimmune diseases under immunosuppression. Pediatr Rheumatol Online J. 2016;14(1):34. doi: 10.1186/s12969-016-0095-3.
    1. Curtis JR, Xie F, Yun H, Bernatsky WKL. Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis. Ann Rheum Dis. 2016;75(10):1843–1847. doi: 10.1136/annrheumdis-2016-209131.
    1. Aeschlimann FA, Chong SL, Lyons TW, Beinvogl BC, Goez-Mogollon LM, Tan S, et al. Risk of serious infections associated with biologic agents in juvenile idiopathic arthritis: a systematic review and meta-analyses. J Pediatr. 2019;204:162–171. doi: 10.1016/j.jpeds.2018.08.065.

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