Statistics

 array:24 [
  "pii" => "S217357432100215X"
  "issn" => "21735743"
  "doi" => "10.1016/j.reumae.2021.06.003"
  "estado" => "S300"
  "fechaPublicacion" => "2022-10-01"
  "aid" => "1552"
  "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología"
  "copyrightAnyo" => "2021"
  "documento" => "simple-article"
  "crossmark" => 1
  "subdocumento" => "crp"
  "cita" => "Reumatol Clin. 2022;18:475-9"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S1699258X21001571"
      "issn" => "1699258X"
      "doi" => "10.1016/j.reuma.2021.06.001"
      "estado" => "S300"
      "fechaPublicacion" => "2022-10-01"
      "aid" => "1552"
      "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología"
      "documento" => "simple-article"
      "crossmark" => 1
      "subdocumento" => "crp"
      "cita" => "Reumatol Clin. 2022;18:475-9"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:1 [
        "total" => 0
      ]
      "es" => array:12 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Original breve</span>"
        "titulo" => "Niveles de f&#225;rmacos anti-TNF&#945; en pacientes con artritis reumatoide y espondiloartritis"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "475"
            "paginaFinal" => "479"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Anti-TNF&#945; Drug Levels in Patients with Rheumatoid Arthritis and Spondyloarthritis"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Erardo Meri&#241;o-Ibarra, Francisco Javier Manero Ru&#237;z"
            "autores" => array:2 [
              0 => array:2 [
                "nombre" => "Erardo"
                "apellidos" => "Meri&#241;o-Ibarra"
              ]
              1 => array:2 [
                "nombre" => "Francisco Javier"
                "apellidos" => "Manero Ru&#237;z"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S217357432100215X"
          "doi" => "10.1016/j.reumae.2021.06.003"
          "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/S217357432100215X?idApp=UINPBA00004M"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X21001571?idApp=UINPBA00004M"
      "url" => "/1699258X/0000001800000008/v1_202210010847/S1699258X21001571/v1_202210010847/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2173574321001684"
    "issn" => "21735743"
    "doi" => "10.1016/j.reumae.2021.04.004"
    "estado" => "S300"
    "fechaPublicacion" => "2022-10-01"
    "aid" => "1554"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Reumatolog&#237;a y Colegio Mexicano de Reumatolog&#237;a"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "Reumatol Clin. 2022;18:480-5"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>"
      "titulo" => "Usefulness of rheumatology consultancy in situ&#58; Analysis of a long-term experience"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "480"
          "paginaFinal" => "485"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Utilidad de la consultor&#237;a reumatol&#243;gica <span class="elsevierStyleItalic">in situ</span>&#58; an&#225;lisis de una experiencia prolongada en el tiempo"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Jes&#250;s Tornero-Molina, Mar&#237;a Luisa D&#237;ez-Andr&#233;s, Fernando Alonso, Cintia de la Llana-Calvo, Susana Luengo Rojo, Elena Casado Silvestre, Raquel Grado Sanz"
          "autores" => array:7 [
            0 => array:2 [
              "nombre" => "Jes&#250;s"
              "apellidos" => "Tornero-Molina"
            ]
            1 => array:2 [
              "nombre" => "Mar&#237;a Luisa"
              "apellidos" => "D&#237;ez-Andr&#233;s"
            ]
            2 => array:2 [
              "nombre" => "Fernando"
              "apellidos" => "Alonso"
            ]
            3 => array:2 [
              "nombre" => "Cintia"
              "apellidos" => "de la Llana-Calvo"
            ]
            4 => array:2 [
              "nombre" => "Susana"
              "apellidos" => "Luengo Rojo"
            ]
            5 => array:2 [
              "nombre" => "Elena"
              "apellidos" => "Casado Silvestre"
            ]
            6 => array:2 [
              "nombre" => "Raquel"
              "apellidos" => "Grado Sanz"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S1699258X21001595"
        "doi" => "10.1016/j.reuma.2021.04.015"
        "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/S1699258X21001595?idApp=UINPBA00004M"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574321001684?idApp=UINPBA00004M"
    "url" => "/21735743/0000001800000008/v1_202210070758/S2173574321001684/v1_202210070758/en/main.assets"
  ]
  "itemAnterior" => array:18 [
    "pii" => "S2173574322001393"
    "issn" => "21735743"
    "doi" => "10.1016/j.reumae.2022.08.002"
    "estado" => "S300"
    "fechaPublicacion" => "2022-10-01"
    "aid" => "1551"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Reumatolog&#237;a y Colegio Mexicano de Reumatolog&#237;a"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "Reumatol Clin. 2022;18:469-74"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>"
      "titulo" => "Anti-Carbamylated Protein Antibodies&#44; Tumour Necrosis Factor Alpha and Insulin Resistance in Egyptian Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "469"
          "paginaFinal" => "474"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Anticuerpos anti-prote&#237;na carbamilada&#44; factor de necrosis tumoral alfa y resistencia a la insulina en pacientes egipcios con artritis reumatoide y lupus eritematoso sist&#233;mico"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0010"
          "etiqueta" => "Fig&#46; 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 1270
              "Ancho" => 1675
              "Tamanyo" => 60313
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Correlation between anti-carP antibody and DAS 28-ESR&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Mohamed Sherif El Hawary, Sarah A&#46; Hassan, Sahar Abd ELatty, Noha M&#46; Khalil"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "Mohamed Sherif"
              "apellidos" => "El Hawary"
            ]
            1 => array:2 [
              "nombre" => "Sarah A&#46;"
              "apellidos" => "Hassan"
            ]
            2 => array:2 [
              "nombre" => "Sahar Abd"
              "apellidos" => "ELatty"
            ]
            3 => array:2 [
              "nombre" => "Noha M&#46;"
              "apellidos" => "Khalil"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574322001393?idApp=UINPBA00004M"
    "url" => "/21735743/0000001800000008/v1_202210070758/S2173574322001393/v1_202210070758/en/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Brief Report</span>"
    "titulo" => "Anti-TNF&#945; drug levels in patients with rheumatoid arthritis and spondyloarthritis"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "475"
        "paginaFinal" => "479"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Erardo Meri&#241;o-Ibarra, Francisco Javier Manero Ru&#237;z"
        "autores" => array:2 [
          0 => array:4 [
            "nombre" => "Erardo"
            "apellidos" => "Meri&#241;o-Ibarra"
            "email" => array:1 [
              0 => "eemerinnoi@salud.aragon.es"
            ]
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:2 [
            "nombre" => "Francisco Javier"
            "apellidos" => "Manero Ru&#237;z"
          ]
        ]
        "afiliaciones" => array:1 [
          0 => array:2 [
            "entidad" => "Servicio de Reumatolog&#237;a&#44; Hospital Universitario Miguel Servet&#44; Zaragoza&#44; Spain"
            "identificador" => "aff0005"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Niveles de f&#225;rmacos anti-TNF&#945; en pacientes con artritis reumatoide y espondiloartritis"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">In patients with rheumatoid arthritis &#40;RA&#41; treated with anti-TNF drugs &#40;anti-TNF&#41;&#46; A correlation has been found between drug levels and clinical response<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; For example&#44; in infliximab-treated patients&#44; the presence of anti-drug antibodies &#40;ADA&#41; provoke loss of response&#44; ifuional reactions and increased treatment withdrawal<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46; These data are not exclusive to RA and have also been described in spondyloarhritis &#40;SpA&#41;&#44; where anti-infliximab and anti-adalimumab antibodies are found in non-responders and in the case of infliximab&#44; they are also related to infusional reactions&#44; motivating a switch to another drug<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Various drug level measurement techniques are available with different standardisation<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#44; creating uncertainty as to the value of measuring drug levels&#46; A consensus article has recently been published with the aim of reducing this uncertainty in the Spanish setting<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The aims of this study were to compare anti-TNF levels in RA patients vs&#46; SpA&#44; in patients in remission&#47;low disease activity &#40;LDA&#41; vs&#46; non-remission&#47;non-LDA according to rheumatic disease&#44; and to determine the influence of the use of conventional synthetic disease-modifying drugs &#40;DMARDs&#41; on these levels&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Material and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">A total of 474 patients were being treated with anti-TNF drugs at our centre&#44; including 51 patients with infliximab&#44; 198 patients with adlmumab&#44; and 225 patients with etanercept&#46; A retrospective&#44; observational study was conducted to measure anti-TNF levels and the presence of ADA in a group of consecutively selected patients who attended consultations at the rheumatology department of the Miguel Servet University Hospital&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Inclusion criteria</span><p id="par0025" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0030" class="elsevierStylePara elsevierViewall">Adult patients on anti-TNF treatment&#46;</p></li></ul></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Exclusion criteria</span><p id="par0035" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0040" class="elsevierStylePara elsevierViewall">Patients who declined to participate in the study</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Patients under follow-up in other hospitals</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Diagnoses other than RA or SpA</p></li></ul></p><p id="par0055" class="elsevierStylePara elsevierViewall">The most commonly used methods for measuring levels are the sandwich ELISA and the indirect ELISA<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46; In our study&#44; the sample was obtained on the day the drug was due to be administered &#40;trough level&#41;&#44; using the Promonitor&#174; test from Laboratorios Grifols &#40;sandwich ELISA&#41;&#44; and according to the methodology described by Chen DY et al&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; In cases with undetectable anti-TNF levels&#44; Acaf was measured using the Promonitor&#174; test from Laboratorios Grifols &#40;bridge-type ELISA&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The following data were collected from the patients&#8217; clinical history&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Time of evolution of the disease</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Type and schedule of biologic treatment and DMARDs</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Adherence&#58; percentage of the prescribed dosage of the drug that the patient withdraws from the hospital pharmacy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Disease activity&#58; considering remission&#47;low activity in patients with RA when they had a DAS28 &#40;CRP&#41;&#8239;&#8804;&#8239;3&#46;2 and in patients with SpA a BASDAI&#8239;&#8804;&#8239;4 and ASDAS &#40;CRP&#41;&#8239;&#8804;&#8239;2&#46;1&#46; The activity indices were obtained from the consultation prior to the measurement of the levels&#46;</p></li></ul></p><p id="par0085" class="elsevierStylePara elsevierViewall">With these data&#44; a group of patients with RA and SpA was obtained and in each&#44; subgroups with drug dosages according to the technical data sheet &#40;standard dose&#41; and others with dosages lower than those recommended &#40;suboptimal dose&#41;&#44; as well as patients with&#47;without treatment with DMARDs&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Ethical aspects</span><p id="par0090" class="elsevierStylePara elsevierViewall">All patients signed an informed consent form for this study and for the use of biological samples for biomedical research&#46; This study was approved by the Research Ethics Committee of the Autonomous Community of Aragon&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical method</span><p id="par0095" class="elsevierStylePara elsevierViewall">Quantitative variables&#58; distribution was determined with the Kolmogorov-Smirnov statistic &#40;Lilliefors correction&#41;&#59; in variables with N&#8239;&#60;&#8239;50&#44; the Shapiro&#8211;Wilk statistic was applied&#59; if the distribution was normal&#44; the mean and standard deviation &#40;SD&#41; were determined&#59; in variables with non-parametric distribution&#44; the median and interquartile range &#40;IQR&#41; were determined&#46; For differences between means and between medians&#58; Student&#8217;s t test and Mann&#8211;Whitney U test were used&#44; respectively&#46; For qualitative variables&#58; 2&#8239;&#215;&#8239;2 contingency tables with Pearson&#8217;s Chi-square test&#46; Statistical procedures were performed with the R statistical programme and calculated with a 95&#37; confidence interval&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0100" class="elsevierStylePara elsevierViewall">A total of 53&#44; 73&#44; and 78 patients on treatment with infliximab&#44; adalimumab&#44; and etanercept&#44; respectively&#44; were studied&#46; In all cases&#44; a single sample extraction was performed&#46; Eleven patients were excluded due to AFA and absence of drug levels&#58; 3 &#40;5&#46;6&#37;&#41; treated with infliximab&#44; all with SpA&#44; none treated with DMARDs&#59; 8 &#40;11&#37;&#41; treated with adalimumab&#44; 2 with RA on leflunomide&#44; 6 patients with SpA&#44; one treated with leflunomide&#44; the remaining 5 without DMARDs&#46; No anti-etanercept antibodies were detected&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">No differences were found in drug levels according to disease type and disease activity&#46; Patients with RA had a median DAS28&#58; 2&#46;79 &#40;RI&#58; 2&#46;27&#8722;3&#46;62&#41; and those with SpA had a BASDAI of 3&#46;47 &#40;SD&#58; 2&#46;2&#41; and an ASDAS of 1&#46;70 &#40;1&#46;40&#8722;2&#46;27&#41;&#46; The variables studied are displayed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">The percentage of remission&#47;LDA in cases with RA and SpA was 74&#46;3&#37; and 77&#46;8&#37;&#44; respectively&#46; The time of disease progression was 12&#46;9 years &#40;RI&#58; 7&#46;49&#8722;22&#46;5&#41;&#44; with no differences between diseases &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#59; adherence was &#8805;80&#37; in 88&#46;6&#37; of cases&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Drug levels in patients on standard-dose anti-TNF were 2&#46;2&#8239;g&#47;mL &#40;1&#46;4&#8211;5&#46;2&#41;&#44; 4&#46;9&#8239;g&#47;mL &#40;0&#46;8&#8722;8&#46;9&#41;&#44; and 3&#46;1&#8239;g&#47;mL &#40;2&#46;3&#8722;4&#46;4&#41; for infliximab&#44; adalimumab and etanercept&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>A&#41;&#44; with no differences according to rheumatic disease &#40;data not shown&#41;&#46; We also found no differences in the group of cases with standard drug dosages&#44; segmented by disease type and activity &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>B&#41;&#46; When dividing patients with standard drug dosages according to treatment with&#47;without DMARDs&#44; we obtained significant differences in serum levels of infliximab and etanercept&#59; adalimumab levels were similar in both groups &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>C&#41;&#44; and subdividing these cases according to rheumatic disease&#44; only etanercept levels exhibited differences in patients with SpA &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>C1&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0120" class="elsevierStylePara elsevierViewall">The drug level achieved after the standard treatment regimen may differ from one patient to another&#59; however&#44; the drug level required to achieve remission may not differ&#44; hence the importance of evidence to support monitoring of anti-TNF6 levels&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The patients studied were fairly homogeneous&#44; even between those in remission and non-remission&#59; for instance&#44; RA patients had generally low activity indices&#44; which may have contributed to differences in drug levels not being conspicuous when comparing patient subgroups&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">With respect to infliximab&#44; the study by Jurado T et al&#46; found that most RA patients in remission at week 54 after perfusion displayed levels of 4&#46;4&#8239;g&#47;mL at week<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> whereas in our study at week 12&#44; we logically found lower levels of infliximab&#44; with no differences in the remission&#47;LDA vs&#46; non-remission&#47;non-LDA groups&#46; Our results show no difference between infliximab levels between RA and SpA&#59; nevertheless&#44; Padilla-Mart&#237;nez EM et al&#46; detected different infliximab trough levels between the 2 diseases<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#44; but did not exclude cases with ADA from the analysis&#59; similarly&#44; they had a smaller sample size&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Sanmarti R et al&#46; found adalimumab levels of 6&#46;9&#8239;g&#47;mL in patients with RA in remission<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46; Pouw MF et al&#46; suggest that they should have levels of between 5&#8722;8&#8239;g&#47;mL<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#44; similar to what was found in our study in patients in remission&#46; Finally&#44; Kneepkens EL et al&#46; obtained an etanercept level of 3&#46;8&#8239;g&#47;mL &#40;2&#46;5&#8211;5&#46;2&#41; in SpA patients with ASDAS&#8239;&#60;&#8239;2&#46;1<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and Sanmarti R et al&#46; obtained etanercept levels of 2&#46;3&#8239;g&#47;mL in RA patients in remission<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46; Our results were similar in both diseases excluding patients with suboptimal doses&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Anti-TNF levels can be affected by different factors such as comorbidity&#44; route of drug administration&#44; ADA formation&#44; or the use of cSFs<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; In our study&#44; we detected differences in drug levels between patients with&#47;without cAMP for infliximab and etanercept&#59; nonetheless&#44; we found no differences for adalimumab levels&#46; However&#44; Vogelzang EH et al&#46; found higher levels of adalimumab in patients with RA or psoriatic arthritis treated with methotrexate<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">In general&#44; we did not find differences in drug levels according to disease activity&#44; perhaps because of the homogeneity of the sample in this aspect&#44; but if we add a cSF-MEF&#44; then differences do emerge&#44; mainly in SpA&#46; Does this suggest the need to always use cSF-MEFs in association with anti-TNFs&#63; Probably not routinely&#44; albeit this opinion might be different if we assessed other biomarkers&#44; such as the CXCL12 genotype or HLA-DQA1&#42;05<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a>&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">One of the limitations of our study is that as it is observational&#44; retrospective&#44; and conducted in clinical practice&#46; As such&#44; we do not aways have the results for all the variables studied&#46; In addition&#44; when the sample was subdivided&#44; it was reduced&#44; in some cases losing representativeness of the population under study&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">In summary&#44; we purport that anti-TNF drug levels will be modified by treatment with cAMP&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Funding</span><p id="par0160" class="elsevierStylePara elsevierViewall">This research has not received any specific public or private funding&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:11 [
        0 => array:3 [
          "identificador" => "xres1779554"
          "titulo" => "Abstract"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Background and objectives"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Objectives"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Materials and methods"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Results"
            ]
            4 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Conclusions"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1562310"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres1779553"
          "titulo" => "Resumen"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Antecedentes y objetivos"
            ]
            1 => array:2 [
              "identificador" => "abst0035"
              "titulo" => "Objetivos"
            ]
            2 => array:2 [
              "identificador" => "abst0040"
              "titulo" => "Materiales y m&#233;todos"
            ]
            3 => array:2 [
              "identificador" => "abst0045"
              "titulo" => "Resultados"
            ]
            4 => array:2 [
              "identificador" => "abst0050"
              "titulo" => "Conclusiones"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec1562311"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Material and methods"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Inclusion criteria"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Exclusion criteria"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Ethical aspects"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Statistical method"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Results"
        ]
        7 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Funding"
        ]
        9 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Conflict of interest"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2020-09-07"
    "fechaAceptado" => "2021-06-03"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1562310"
          "palabras" => array:3 [
            0 => "Anti-TNF&#945; levels"
            1 => "Rheumatoid arthritis"
            2 => "Spondyloarthritis"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1562311"
          "palabras" => array:3 [
            0 => "Niveles de anti-TNF&#945;"
            1 => "Artritis reumatoide"
            2 => "Espondiloartritis"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objectives</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Knowledge of the levels of anti-TNFa drugs can modify treatment in patients with rheumatoid arthritis &#40;RA&#41; and spondyloarthritis &#40;SpA&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">To compare the levels of anti-TNFa in patients with RA vs SpA&#44; in different clinical situations&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Materials and methods</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A retrospective&#44; observational study was conducted&#46; Levels of anti-TNFa and the presence of anti-drug antibodies were measured in consecutively selected patients&#44; using the ELISA technique&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Fifty-three&#44; 73 and 78 patients treated with infliximab&#44; adalimumab and etanercept were studied&#44; respectively&#46; The median drug levels in patients using standard doses were infliximab 2&#46;2&#8239;&#181;g&#47;mL &#40;1&#46;4&#8211;5&#46;2&#41;&#44; adalimumab 4&#46;9&#8239;&#181;g&#47;mL &#40;0&#46;8&#8722;8&#46;9&#41; and etanercept 3&#46;1&#8239;&#181;g&#47;mL &#40;2&#46;3&#8722;4&#46;4&#41;&#46; There were no differences in drug levels according to disease activity but we found differences in etanercept and infliximab levels according to DMARD use&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Levels of anti-TNFa drugs will change with DMARD treatment&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background and objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objectives"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Materials and methods"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Results"
          ]
          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Antecedentes y objetivos</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">El conocimiento de los niveles de f&#225;rmacos anti-TNF&#945; puede modificar el tratamiento en pacientes con artritis reumatoide &#40;AR&#41; y espondiloartritis &#40;EspA&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Comparar los niveles de anti-TNF&#945; en pacientes con AR vs EspA&#44; en diferentes situaciones cl&#237;nicas&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Materiales y m&#233;todos</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un estudio retrospectivo&#44; observacional donde se midieron los niveles de anti-TNF&#945; y la presencia de anticuerpos antif&#225;rmacos en pacientes seleccionados consecutivamente&#44; utilizando la t&#233;cnica de ELISA&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Se estudiaron 53&#44; 73 y 78 pacientes en tratamiento con infliximab&#44; adalimumab y etanercept&#44; respectivamente&#46; Los niveles medios de f&#225;rmaco en pacientes con dosis est&#225;ndar fueron&#58; infliximab 2&#44;2&#8239;&#956;g&#47;mL &#40;1&#44;4&#8211;5&#44;2&#41;&#44; adalimumab 4&#44;9&#8239;&#956;g&#47;mL &#40;0&#44;8&#8722;8&#44;9&#41; y etanercept 3&#44;1&#8239;&#956;g&#47;mL &#40;2&#44;3&#8211;4&#44;4&#41;&#46; No se encontraron diferencias en los niveles f&#225;rmacos seg&#250;n la actividad de la enfermedad&#44; sin embargo&#44; hubo diferencias en los niveles de etanercept e infliximab seg&#250;n el uso de f&#225;rmacos modificadores de la enfermedad sint&#233;ticos &#40;FAMEsc&#41;&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Los niveles de f&#225;rmacos anti-TNF&#945; se ver&#225;n modificados por el tratamiento con FAMEsc&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Antecedentes y objetivos"
          ]
          1 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Objetivos"
          ]
          2 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Materiales y m&#233;todos"
          ]
          3 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "Resultados"
          ]
          4 => array:2 [
            "identificador" => "abst0050"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Meri&#241;o-Ibarra E&#44; Manero Ru&#237;z FJ&#46; Niveles de f&#225;rmacos anti-TNF&#945; en pacientes con artritis reumatoide y espondiloartritis&#46; Reumatol Cl&#237;n&#46; 2022&#59;18&#58;475&#8211;479&#46;</p>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">ASDAS&#58; Ankylosing Spondylitis Disease Activity Score&#59; BASDAI&#58; Bath Ankylosing Spondylitis Disease Activity Index&#59; BMI&#58; Body Mass Index&#59; CRP&#58; C-reactive protein&#59; DAS28&#58; Disease Activity Score 28-joint counts&#59; DMARDs&#58; synthetic disease-modifying drugs&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Rheumatoid arthritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Spondyloarthritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col"><span class="elsevierStyleItalic">P</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#8239;&#61;&#8239;74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#8239;&#61;&#8239;119&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#8239;&#61;&#8239;193&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Age &#40;years&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#46;8 &#40;12&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#46;7 &#40;14&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#46;7 &#40;13&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Women&#44; N &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57 &#40;77&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44 &#40;36&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">101 &#40;52&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Infliximab &#40;g&#47;mL&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;10 &#40;1&#46;70&#8722;3&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;9 &#40;0&#46;85&#8722;6&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;3 &#40;1&#46;0&#8722;5&#46;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;546&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Adalimumab &#40;g&#47;mL&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;80 &#40;1&#46;80&#8722;6&#46;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;40 &#40;1&#46;50&#8722;8&#46;95&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;80 &#40;1&#46;80&#8722;8&#46;60&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;272&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Etanercept &#40;g&#47;mL&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;60 &#40;1&#46;20&#8722;4&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n