Letter to the Editor
Use of anakinra in the treatment of SARS-CoV-2 severe respiratory infection
Uso de anakinra en el tratamiento de la infección respiratoria grave por SARS-CoV-2
Read
1363
Timeswas read the article
478
Total PDF
885
Total HTML
Share statistics
array:24 [ "pii" => "S2173574322000971" "issn" => "21735743" "doi" => "10.1016/j.reumae.2022.02.001" "estado" => "S300" "fechaPublicacion" => "2023-02-01" "aid" => "1603" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología" "copyrightAnyo" => "2022" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Reumatol Clin. 2023;19:121" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S1699258X22000699" "issn" => "1699258X" "doi" => "10.1016/j.reuma.2022.02.003" "estado" => "S300" "fechaPublicacion" => "2023-02-01" "aid" => "1603" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Reumatol Clin. 2023;19:121" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta al Editor</span>" "titulo" => "Uso de anakinra en el tratamiento de la infección respiratoria grave por SARS-CoV-2" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:1 [ "paginaInicial" => "121" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Use of anakinra in the treatment of SARS-CoV-2 severe respiratory infection" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Luis Figuero-Pérez, Alejandro Olivares-Hernández, Roberto A. Escala-Cornejo, Juan J. Cruz-Hernández" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Luis" "apellidos" => "Figuero-Pérez" ] 1 => array:2 [ "nombre" => "Alejandro" "apellidos" => "Olivares-Hernández" ] 2 => array:2 [ "nombre" => "Roberto A." "apellidos" => "Escala-Cornejo" ] 3 => array:2 [ "nombre" => "Juan J." "apellidos" => "Cruz-Hernández" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173574322000971" "doi" => "10.1016/j.reumae.2022.02.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574322000971?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X22000699?idApp=UINPBA00004M" "url" => "/1699258X/0000001900000002/v1_202301310743/S1699258X22000699/v1_202301310743/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2173574322000995" "issn" => "21735743" "doi" => "10.1016/j.reumae.2022.06.002" "estado" => "S300" "fechaPublicacion" => "2023-02-01" "aid" => "1595" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Reumatol Clin. 2023;19:122" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Comment: The reality of rheumatology in Spain and its autonomous communities before the pandemic" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:1 [ "paginaInicial" => "122" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Comentario a: Realidad de la Reumatología en España y sus comunidades autónomas antes de la pandemia" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Dolors Grados Cànovas, Melania Martínez-Morillo, Alejandro Olivé Marqués" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Dolors" "apellidos" => "Grados Cànovas" ] 1 => array:2 [ "nombre" => "Melania" "apellidos" => "Martínez-Morillo" ] 2 => array:2 [ "nombre" => "Alejandro" "apellidos" => "Olivé Marqués" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1699258X22000274" "doi" => "10.1016/j.reuma.2021.11.006" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X22000274?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574322000995?idApp=UINPBA00004M" "url" => "/21735743/0000001900000002/v1_202302031212/S2173574322000995/v1_202302031212/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S217357432200096X" "issn" => "21735743" "doi" => "10.1016/j.reumae.2022.06.001" "estado" => "S300" "fechaPublicacion" => "2023-02-01" "aid" => "1599" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Reumatol Clin. 2023;19:120-1" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Anakinra as a potential alternative in the treatment of severe acute respiratory infection associated with SARS-CoV-2 refractory to tocilizumab: comment" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "120" "paginaFinal" => "121" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Anakinra, una alternativa potencial en el tratamiento de la infección respiratoria grave por SARS-CoV-2 refractaria a tocilizumab: comentario" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ismael Francisco Aomar-Millán, Juan Salvatierra, José Luis Callejas-Rubio, Enrique Raya-Álvarez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Ismael Francisco" "apellidos" => "Aomar-Millán" ] 1 => array:2 [ "nombre" => "Juan" "apellidos" => "Salvatierra" ] 2 => array:2 [ "nombre" => "José Luis" "apellidos" => "Callejas-Rubio" ] 3 => array:2 [ "nombre" => "Enrique" "apellidos" => "Raya-Álvarez" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1699258X22000468" "doi" => "10.1016/j.reuma.2022.01.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X22000468?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217357432200096X?idApp=UINPBA00004M" "url" => "/21735743/0000001900000002/v1_202302031212/S217357432200096X/v1_202302031212/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Use of anakinra in the treatment of SARS-CoV-2 severe respiratory infection" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:1 [ "paginaInicial" => "121" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Luis Figuero-Pérez, Alejandro Olivares-Hernández, Roberto A. Escala-Cornejo, Juan J. Cruz-Hernández" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Luis" "apellidos" => "Figuero-Pérez" "email" => array:1 [ 0 => "figuero44@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Alejandro" "apellidos" => "Olivares-Hernández" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Roberto A." "apellidos" => "Escala-Cornejo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Juan J." "apellidos" => "Cruz-Hernández" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Oncología Médica, Complejo Asitencial Universitario de Salamanca, Salamanca, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Instituto de Investigación Nacional (SOLCA) de Guayaquil, Guayaquil, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Uso de anakinra en el tratamiento de la infección respiratoria grave por SARS-CoV-2" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We would first like to thank Aomar-Millán et al.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> for their response to our article in which we suggested the potential benefit of anakinra in the treatment of SARS-CoV-2 infection refractory to tocilizumab treatment.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The “cytokine storm” secondary to SARS-CoV-2 infection leads to severe COVID-19 disease. Excessive activation of the immune system produces a picture like that of HLH.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Increased levels of proinflammatory cytokines (IL-1, IL-6, or TNF-alpha), procoagulant factors and lymphopenia play a major role in its pathogenesis.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The use of immunosuppressants such as dexamethasone and anti-IL-6 (tocilizumab) and anti-IL-1 (anakinra) antibodies are the mainstay of treatment of the inflammatory phase of SARS-CoV-2 infection.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">As reported by Aomar-Millán et al., anakinra has recently been approved by the EMA for the treatment of patients with SARS-CoV-2 pneumonia who require supplemental oxygen therapy and who are at risk of progressing to severe respiratory failure as determined by a plasma concentration of soluble urokinase-type plasminogen activator receptor (suPAR) ≥6<span class="elsevierStyleHsp" style=""></span>ng/mL. This approval was based on the SAVE MORE study,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> which demonstrated a decrease in mortality and hospital stay in patients treated early with anakinra.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Interestingly, the retrospective study by Aomar-Millán et al.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> analysed 143 patients with SARS-CoV-2 pneumonia. Patients refractory to treatment with corticosteroids and tocilizumab were treated with anakinra at a dose of 100<span class="elsevierStyleHsp" style=""></span>mg/every 8−12<span class="elsevierStyleHsp" style=""></span>h between day 2 and 6. Administration of anakinra was associated with a reduced risk of mortality (HR: .518; 95% CI: .265<span class="elsevierStyleHsp" style=""></span>–<span class="elsevierStyleHsp" style=""></span>.910; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.0437).</p><p id="par0030" class="elsevierStylePara elsevierViewall">The patient described in our article<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> received 2 doses of tocilizumab (8<span class="elsevierStyleHsp" style=""></span>mg/kg, subcutaneously) and, given the absence of respiratory and analytical improvement 48<span class="elsevierStyleHsp" style=""></span>h after tocilizumab administration, it was decided to administer anakinra (100<span class="elsevierStyleHsp" style=""></span>mg single total dose, subcutaneously). At the time the patient was admitted to hospital (April 2020), the use of anakinra in the inflammatory phase of SARS-CoV-2 pneumonia was under study. Therefore, no recommended dose had been described in the literature at that time. Currently, although there is still no consensus, higher doses and several days of continuous treatment are recommended.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–7</span></a> Like Aomar-Millán et al. in their response, we considered in the discussion of our article that the clinical improvement of the patient could not be explained solely by the effect of treatment with anakinra, and that a late benefit of tocilizumab should not be ruled out.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interests</span><p id="par0035" class="elsevierStylePara elsevierViewall">JJC-H: Consulting or Advisory Role: MSD Oncology, Bristol-Myers Squibb, Merck Speakers’ Bureau: MSD Oncology, Bristol-Myers Squibb, Merck, Roche, Janssen Oncology, AstraZeneca Travel, Accommodations, Expenses: MSD Oncology; the remaining authors have no conflict of interests to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interests" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-02-01" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Figuero-Pérez L, Olivares-Hernández A, Escala-Cornejo RA, Cruz-Hernández JJ. Uso de anakinra en el tratamiento de la infección respiratoria grave por SARS-CoV-2. Reumatol Clin. 2023;19:122.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Aomar-Millán IF, Salvatierra J, Callejas-Rubio JL, Raya-Álvarez E. Anakinra, una alternativa potencial en el tratamiento de la infección respiratoria grave por SARS-CoV-2 refractaria a tocilizumab: comentario. Reumatol Clin. DOI: 10.1016/j.reuma.2022.01.003." ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anakinra as a potential alternative in the treatment of severe acute respiratory infection associated with SARS-CoV-2 refractory to tocilizumab" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "L. Figuero-Pérez" 1 => "A. Olivares-Hernández" 2 => "R.A. Escala-Cornejo" 3 => "E. Terán-Brage" 4 => "Á López-Gutiérrez" 5 => "J.J. Cruz-Hernández" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.reumae.2020.06.008" "Revista" => array:6 [ "tituloSerie" => "Reumatol Clin (Engl Ed)" "fecha" => "2021" "volumen" => "17" "paginaInicial" => "559" "paginaFinal" => "561" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34823820" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anakinra for macrophage activation syndrome may hold lessons for treatment of cytokine storm in the setting of COVID19" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "T.L. Wampler Muskardin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/acr2.11140" "Revista" => array:3 [ "tituloSerie" => "ACR Open Rheumatol." "fecha" => "2020" "volumen" => "2" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systematic review and meta-analysis of anakinra, sarilumab, siltuximab and tocilizumab for COVID-19" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.A. Khan" 1 => "I. Stewart" 2 => "L. Fabbri" 3 => "S. Moss" 4 => "K. Robinson" 5 => "A.R. Smyth" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thoraxjnl-2020-215266" "Revista" => array:7 [ "tituloSerie" => "Thorax." "fecha" => "2021" "volumen" => "76" "numero" => "9" "paginaInicial" => "907" "paginaFinal" => "919" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33579777" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Kyriazopoulou" 1 => "G. Poulakou" 2 => "H. Milionis" 3 => "S. Metallidis" 4 => "G. Adamis" 5 => "K. Tsiakos" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/s41591-021-01499-z" "Revista" => array:7 [ "tituloSerie" => "Nat Med." "fecha" => "2021" "volumen" => "27" "numero" => "10" "paginaInicial" => "1752" "paginaFinal" => "1760" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34480127" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anakinra after treatment with corticosteroids alone or with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammation. A retrospective cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I.F. Aomar-Millán" 1 => "J. Salvatierra" 2 => "Ú Torres-Parejo" 3 => "N. Faro-Miguez" 4 => "J.L. Callejas-Rubio" 5 => "A. Ceballos-Torres" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11739-020-02600-z" "Revista" => array:4 [ "tituloSerie" => "Intern Emerg Med." "fecha" => "2021" "paginaInicial" => "843" "paginaFinal" => "852" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An open label trial of anakinra to prevent respiratory failure in COVID-19" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Kyriazopoulou" 1 => "P. Panagopoulos" 2 => "S. Metallidis" 3 => "G.N. Dalekos" 4 => "G. Poulakou" 5 => "N. Gatselis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7554/eLife.66125" "Revista" => array:3 [ "tituloSerie" => "Elife." "fecha" => "2021" "volumen" => "10" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000001900000002/v1_202302031212/S2173574322000971/v1_202302031212/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/21735743/0000001900000002/v1_202302031212/S2173574322000971/v1_202302031212/en/main.pdf?idApp=UINPBA00004M&text.app=https://www.reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574322000971?idApp=UINPBA00004M" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 27 | 17 | 44 |
| 2024 September | 68 | 26 | 94 |
| 2024 August | 83 | 51 | 134 |
| 2024 July | 61 | 40 | 101 |
| 2024 June | 65 | 32 | 97 |
| 2024 May | 55 | 28 | 83 |
| 2024 April | 62 | 21 | 83 |
| 2024 March | 70 | 31 | 101 |
| 2024 February | 66 | 34 | 100 |
| 2024 January | 65 | 24 | 89 |
| 2023 December | 49 | 30 | 79 |
| 2023 November | 47 | 42 | 89 |
| 2023 October | 40 | 33 | 73 |
| 2023 September | 64 | 40 | 104 |
| 2023 August | 48 | 23 | 71 |
| 2023 March | 15 | 6 | 21 |
Show all
