Letter to the Editor
Efficacy of Tocilizumab in Refractory Adult-Onset Still's Disease; Report of 2 Cases
Eficacia de tocilizumab en enfermedad de Still del adulto refractaria; a propósito de 2 casos
Lilia Andrade-Ortega
, Fedra Irazoque-Palazuelos, Sandra Muñoz-López, Victor M. Rosales-Don Pablo
Corresponding author
Servicio de Reumatología, Centro Médico Nacional 20 de Noviembre, ISSSTE, Mexico City, Mexico
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Rosales-Don Pablo" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Lilia" "apellidos" => "Andrade-Ortega" "email" => array:1 [ 0 => "liliaandrade@prodigy.net.mx" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Fedra" "apellidos" => "Irazoque-Palazuelos" ] 2 => array:2 [ "nombre" => "Sandra" "apellidos" => "Muñoz-López" ] 3 => array:2 [ "nombre" => "Victor M." "apellidos" => "Rosales-Don Pablo" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Reumatología, Centro Médico Nacional 20 de Noviembre, ISSSTE, Mexico City, Mexico" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Eficacia de tocilizumab en enfermedad de Still del adulto refractaria; a propósito de 2 casos" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Adult Still's disease is an entity of uncommon autoimmune origin, characterized from the physiopathogenic point of view by increased production of inflammatory cytokines, mainly tumor necrosis factor, interleukin 1 (IL-1) and IL-6.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Recently, we employed tocilizumab treatment with a good response in 2 patients with adult Still's disease, both with failure to respond to treatment with glucocorticoids and nonbiological disease modifying drugs.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Patient 1 is a 50-year-old woman, diagnosed with adult Still's disease in 2003 due to daily evening fever >39<span class="elsevierStyleHsp" style=""></span>°<span class="elsevierStyleSmallCaps">C,</span> symmetric polyarthritis, generalized myalgia, evanescent salmon rash on the trunk and limbs, together with elevated acute phase reactants and increased ferritin level (1700<span class="elsevierStyleHsp" style=""></span>ng/ml). Other autoimmune, infectious and neoplastic causes were ruled out. In a span of eight years, she received nonsteroidal anti-inflammatory drugs, glucocorticoids in varying doses, antimalarials, sulfasalazine, methotrexate, leflunomide, azathioprine, rituximab, etanercept and infliximab, with partial response and multiple relapses. In March 2011, due to the persistence of fever, polyarthritis and elevated acute phase reactants, treatment was started with tocilizumab 8<span class="elsevierStyleHsp" style=""></span>mg/kg/month methotrexate 15<span class="elsevierStyleHsp" style=""></span>mg/week and prednisone 15<span class="elsevierStyleHsp" style=""></span>mg/day. A good response was observed after 4 weeks of treatment, which persists to date with improvement of general condition of the skin and joints, no fever and improvement of acute phase reactants. Dyslipidemia occurred as an adverse event, which warranted special treatment.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Patient 2 is a 53-year-old woman with a history of breast cancer in 1997, treated and without tumor activity. In October 2009 she presented maculopapular rash, daily fever, arthritis, myalgias, and weight loss of 11<span class="elsevierStyleHsp" style=""></span>kg in 4 months. She also had hepatosplenomegaly and generalized lymphadenopathy, normochromic normocytic anemia, neutrophilia, thrombocytosis, erythrocyte sedimentation rate (ESR) 67<span class="elsevierStyleHsp" style=""></span>mm/h, C-reactive protein (CRP) 84<span class="elsevierStyleHsp" style=""></span>mg/l and ferritin 1900<span class="elsevierStyleHsp" style=""></span>ng/ml. Myeloproliferative and infectious processes were ruled out. Still's disease was diagnosed and she received treatment with methotrexate 20<span class="elsevierStyleHsp" style=""></span>mg/week and prednisone in an initial dose of 1<span class="elsevierStyleHsp" style=""></span>mg/kg, with gradual reduction to 20<span class="elsevierStyleHsp" style=""></span>mg/day in 4 months, persisting with joint pain, myalgia, rash and malaise. We added tocilizumab treatment 8<span class="elsevierStyleHsp" style=""></span>mg/kg/month, with a good clinical response and significant improvement in acute phase reactants. So far, she has had no adverse events and is under close surveillance due to the history of neoplasia.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Both cases presented had adult onset Still's disease treated with tocilizumab and a very good response to treatment, almost from the first week, improvement in the clinical manifestations of fever, rash and arthropathy, and a frank and rapid reduction in the acute phase reactants (WBC, CRP, ESR). This is similar to the cases reported in the literature that relate very significant improvement of clinical manifestations and acute inflammatory response even in refractory patients with multiple prior therapies. As in the case of our patients, the majority of reports describe that the response is maintained and adverse effects, particularly dyslipidemia, improve with specific treatment.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–11</span></a> Although the data available to date are still limited due to the rarity of the disease and limited availability of anti-IL-6 treatment, it seems clear that the use of tocilizumab represents a good alternative for the treatment of this disease, which can be chronic and potentially disabling. Our patients are the first to be reported in Latin American literature.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Andrade-Ortega L, Irazoque-Palazuelos F, Muñoz-López S, Rosales-Don Pablo VM. Eficacia de tocilizumab en enfermedad de Still del adulto refractaria; a propósito de 2 casos. Reumatol Clin. 2014;10:199–200.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adult onset Still's disease: review of 41 cases" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Riera" 1 => "A. Olivé" 2 => "J. Narváez" 3 => "S. Holgado" 4 => "P. Santo" 5 => "L. Mateo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Exp Rheumatol" "fecha" => "2011" "volumen" => "29" "paginaInicial" => "331" "paginaFinal" => "336" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21385548" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pathogenesis and management of adult-onset Still's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P. Efthimiou" 1 => "S. Georgy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.semarthrit.2006.07.001" "Revista" => array:6 [ "tituloSerie" => "Semin Arthritis Rheum" "fecha" => "2006" "volumen" => "36" "paginaInicial" => "144" "paginaFinal" => "152" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16949136" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tocilizumab in the treatment of the adult-onset Still's disease: current clinical evidence" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "H. de Boysson" 1 => "J. Février" 2 => "A. Nicolle" 3 => "C. Auzary" 4 => "L. Geffray" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-012-2105-2" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2013" "volumen" => "32" "paginaInicial" => "141" "paginaFinal" => "147" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23108887" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tocilizumab in refractory adult Still's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "X. Puéchal" 1 => "M. DeBandt" 2 => "J.M. Berthelot" 3 => "M. Breban" 4 => "J.J. Dubost" 5 => "O. Fain" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Arthritis Care Res (Hoboken)" "fecha" => "2011" "volumen" => "63" "paginaInicial" => "155" "paginaFinal" => "159" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful treatment of adult-onset Still's disease with tocilizumab monotherapy: two case reports and literature review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Sakai" 1 => "H. Nagasawa" 2 => "E. Nishi" 3 => "A. Okuyama" 4 => "H. Takei" 5 => "T. Kurasawa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-011-1917-9" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2012" "volumen" => "31" "paginaInicial" => "569" "paginaFinal" => "574" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22215118" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A case report of a patient with refractory adult-onset Still's disease who was successfully treated with tocilizumab over 6 years" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H. Nakahara" 1 => "T. Mima" 2 => "N. Yoshio-Hoshino" 3 => "M. Matsushita" 4 => "J. Hashimoto" 5 => "N. Nishimoto" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10165-008-0116-2" "Revista" => array:6 [ "tituloSerie" => "Mod Rheumatol" "fecha" => "2009" "volumen" => "19" "paginaInicial" => "69" "paginaFinal" => "72" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18762861" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tocilizumab in refractory adult-onset Still's disease with aseptic meningitis-efficacy of interleukin-6 blockade and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G.R. Sabnis" 1 => "Y.A. Gokhale" 2 => "U.P. Kulkarni" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.semarthrit.2010.05.003" "Revista" => array:6 [ "tituloSerie" => "Semin Arthritis Rheum" "fecha" => "2011" "volumen" => "40" "paginaInicial" => "365" "paginaFinal" => "368" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20621335" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of refractory adult-onset Still's disease with tocilizumab: report of two cases and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R. Thonhofer" 1 => "M. Hiller" 2 => "H. Just" 3 => "M. Trummer" 4 => "C. Siegel" 5 => "C. Dejaco" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00296-010-1631-y" "Revista" => array:6 [ "tituloSerie" => "Rheumatol Int" "fecha" => "2011" "volumen" => "31" "paginaInicial" => "1653" "paginaFinal" => "1656" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21240503" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A case of refractory adult-onset Still's disease successfully controlled with tocilizumab and a review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K. Perdan-Pirkmajer" 1 => "S. Praprotnik" 2 => "M. Tomšič" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-010-1553-9" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2010" "volumen" => "29" "paginaInicial" => "1465" "paginaFinal" => "1467" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20734215" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful treatment of adult-onset Still's disease refractory to TNF and IL-1 blockade by IL-6 receptor blockade" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Rech" 1 => "M. Ronneberger" 2 => "M. Englbrecht" 3 => "S. Finzel" 4 => "J. Katzenbeisser" 5 => "K. Manger" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2010.129403" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2011" "volumen" => "70" "paginaInicial" => "390" "paginaFinal" => "392" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20650873" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Therapeutic response of patients with adult Still's disease to biologic agents: multicenter results in Japan" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Suematsu" 1 => "A. Ohta" 2 => "E. Matsuura" 3 => "H. Takahashi" 4 => "T. Fujii" 5 => "T. Horiuchi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10165-011-0569-6" "Revista" => array:6 [ "tituloSerie" => "Mod Rheumatol" "fecha" => "2012" "volumen" => "22" "paginaInicial" => "712" "paginaFinal" => "719" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22160845" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000001000000003/v2_201406190029/S2173574313001536/v2_201406190029/en/main.assets" "Apartado" => array:4 [ "identificador" => "8400" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735743/0000001000000003/v2_201406190029/S2173574313001536/v2_201406190029/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574313001536?idApp=UINPBA00004M" ]
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| 2022 February | 74 | 45 | 119 |
| 2022 January | 78 | 46 | 124 |
| 2021 December | 49 | 33 | 82 |
| 2021 November | 37 | 58 | 95 |
| 2021 October | 57 | 51 | 108 |
| 2021 September | 28 | 37 | 65 |
| 2021 August | 45 | 42 | 87 |
| 2021 July | 46 | 32 | 78 |
| 2021 June | 34 | 39 | 73 |
| 2021 May | 47 | 31 | 78 |
| 2021 April | 83 | 45 | 128 |
| 2021 March | 48 | 24 | 72 |
| 2021 February | 43 | 13 | 56 |
| 2021 January | 31 | 13 | 44 |
| 2020 December | 23 | 14 | 37 |
| 2020 November | 26 | 11 | 37 |
| 2020 October | 24 | 8 | 32 |
| 2020 September | 35 | 26 | 61 |
| 2020 August | 29 | 25 | 54 |
| 2020 July | 21 | 16 | 37 |
| 2020 June | 27 | 32 | 59 |
| 2020 May | 36 | 19 | 55 |
| 2020 April | 25 | 12 | 37 |
| 2020 March | 9 | 4 | 13 |
| 2020 February | 1 | 0 | 1 |
| 2018 May | 4 | 1 | 5 |
| 2018 April | 38 | 8 | 46 |
| 2018 March | 47 | 6 | 53 |
| 2018 February | 29 | 8 | 37 |
| 2018 January | 28 | 2 | 30 |
| 2017 December | 40 | 5 | 45 |
| 2017 November | 34 | 6 | 40 |
| 2017 October | 34 | 7 | 41 |
| 2017 September | 37 | 3 | 40 |
| 2017 August | 39 | 10 | 49 |
| 2017 July | 32 | 9 | 41 |
| 2017 June | 47 | 10 | 57 |
| 2017 May | 61 | 24 | 85 |
| 2017 April | 33 | 6 | 39 |
| 2017 March | 37 | 6 | 43 |
| 2017 February | 28 | 4 | 32 |
| 2017 January | 21 | 6 | 27 |
| 2016 December | 71 | 16 | 87 |
| 2016 November | 52 | 4 | 56 |
| 2016 October | 66 | 11 | 77 |
| 2016 September | 59 | 8 | 67 |
| 2016 August | 60 | 8 | 68 |
| 2016 July | 27 | 3 | 30 |
| 2015 December | 2 | 0 | 2 |
| 2015 September | 2 | 0 | 2 |
| 2015 August | 1 | 0 | 1 |
| 2015 July | 11 | 7 | 18 |
| 2015 June | 22 | 6 | 28 |
| 2015 May | 62 | 9 | 71 |
| 2015 April | 84 | 9 | 93 |
| 2015 March | 77 | 4 | 81 |
| 2015 February | 61 | 5 | 66 |
| 2015 January | 53 | 7 | 60 |
| 2014 December | 39 | 7 | 46 |
| 2014 November | 37 | 9 | 46 |
| 2014 October | 38 | 12 | 50 |
| 2014 September | 22 | 8 | 30 |
| 2014 August | 32 | 14 | 46 |
| 2014 July | 21 | 13 | 34 |
| 2014 June | 38 | 17 | 55 |
| 2014 May | 25 | 16 | 41 |
Show all
