Letter to the Editor
Transaminase Elevation Secondary to the Use of Adalimumab
Elevación de transaminasas secundaria a uso de adalimumab
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Fernández-Ávila" "autores" => array:4 [ 0 => array:3 [ "nombre" => "Marietta Luz" "apellidos" => "Juan-Guardela" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Lisseth Fernanda" "apellidos" => "Marín-Carrillo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Laura Ximena" "apellidos" => "Kattah-Martínez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:4 [ "nombre" => "Daniel G." "apellidos" => "Fernández-Ávila" "email" => array:1 [ 0 => "danielfernandezmd@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Departamento de Medicina Interna, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Bogotá, Colombia" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Reumatología, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Grupo Javeriano de Investigación en Enfermedades Reumáticas, Bogotá, Colombia" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Elevación de transaminasas secundaria a uso de adalimumab" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by sacroiliac inflammation and inflammatory low back pain. It belongs to the spondyloarthritis group of disease, which has the common denominator of the presence of sacroiliitis, extra-articular manifestations and HLA-B27 positivity.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Conventional treatment with disease modifying antirheumatic drugs (DMARDs) has limited efficacy, particularly in patients with axial involvement, due to which the use of biologic therapy with monoclonal antibodies against tumor necrosis factor (anti-TNF), including adalimumab, was introduced and which has led to<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> improved clinical responses. Among the adverse events of anti-TNF drugs, there are reported cases of elevated liver enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT),<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> and even<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> subacute liver failure.</p><p id="par0015" class="elsevierStylePara elsevierViewall">We report the case of a 32-year-old man with AS of 2 years evolution, HLA-B27 positive, with a poor response to sulfasalazine 1<span class="elsevierStyleHsp" style=""></span>g/8<span class="elsevierStyleHsp" style=""></span>h, and NSAIDsl, who had persistent severe pain in the lumbosacral region associated with stiffness and functional limitation. Physical examination revealed pain on the sacroiliac joints and arc movement limitation. MRI evidenced spinal osteitis, spinal cord edema and early changes of sacroiliac ankylosis.</p><p id="par0020" class="elsevierStylePara elsevierViewall">AS was considered as in progression, with a high score on the BASFI and BASDAI scales, for which treatment with adalimumab was initiated at a dose of 40<span class="elsevierStyleHsp" style=""></span>mg every 15 days, achieving an adequate clinical response. During follow-up, progressive elevation of aminotransferases was documented, with bilirubin and alkaline phosphatase within normal limits. Since at that time the patient had received no other medication, possible hepatotoxicity adalimumab was suspected, so the biological therapy (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) was suspended with a decline in the aminotransferase levels. A diagnostic test was done with the administration of another dose of adalimumab, once aminotransferases normalized, with a new elevation thereof seen, confirming the case as drug-induced. The diagnostic approach was complemented with tests for viral B and C hepatitis virus, anti-smooth muscle, antimitochondrial antibodies and liver biopsy, ruling out an autoimmune origin.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Anti-TNF therapy may cause hepatotoxicity, which can range from alterations in liver function tests to cases of severe liver failure, through reactivation of viral hepatitis.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Hagel et al. published a case of a patient aged 44 with a history of psoriasis without liver disease, who developed subacute liver failure 4 months after treatment with adalimumab. After discontinuation of therapy and initiation of prednisone, a decrease in aminotransferase levels to normal was documented. The same authors reported mild elevation of aminotransferases, up to 3 times the reference value in 1%–4% of patients treated.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Van der Heijde et al., in 208 AS patients treated with adalimumab, reported at week 12 of follow-up, elevated aminotransferases in 6 patients, with ALT levels 3 times above the reference value, and subsequent normalization of levels in 4 of them without suspension. At 24-weeks of follow-up, only 6 patients (2.8%) had serious adverse events, including one case of elevated liver enzymes in need of liver biopsy in a patient with moderate alcohol consumption and concomitant treatment with indomethacin.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">A Japanese study documented hepatic adverse event in 31.7% of patients treated with adalimumab, including elevated aminotransferases, up to 2.5 times normal, and hepatic steatosis. In neither case was it considered a serious episode and did not require discontinuation of the drug. Cases of hepatitis B reactivation beginning with elevated aminotransferases have also been reported.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Researchers of the CORRONA (Consortium of Rheumatology Researchers of North America) data collection program compared patients receiving anti-TNF therapy (infliximab, etanercept or adalimumab) and who had alterations in liver function tests, and found the following odds ratios for an increase of >2 times in liver function tests: infliximab 2.4 (95% CI: 1.53–3.76), adalimumab 1.72 (95% CI: 0.99–3.01) and etanercept 1.1 (95% CI: 0.64–1.88); however, they noted that the frequency of this disorder is rare.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Our case presented elevated aminotransferases after initiation of adalimumab therapy, which resolved following discontinuation of the drug.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The elevation of aminotransferases is an effect that can occur in patients with AS receiving anti-TNF treatment, however, its progression to severe hepatitis is rare and in most patients is a temporary adverse event that resolves spontaneously and does not produce symptoms.</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of Interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of Interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Juan-Guardela ML, Marín-Carrillo LF, Kattah-Martínez LX, Fernández-Ávila DG. Elevación de transaminasas secundaria a uso de adalimumab. Reumatol Clin. 2014;10:265–266.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Normal value of AST up to 32<span class="elsevierStyleHsp" style=""></span>U/l and ALT up to 40<span class="elsevierStyleHsp" style=""></span>U/l.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Baseline \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Week 4 \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Week 8 \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Week 12 \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Week 20 \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Suspension \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Restart \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">AST \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18<span class="elsevierStyleHsp" style=""></span>U/l \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23<span class="elsevierStyleHsp" style=""></span>U/l \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61<span class="elsevierStyleHsp" style=""></span>U/l \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="char" valign="\n \t\t\t\t\ttop\n 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 97 | 22 | 119 |
| 2024 September | 173 | 14 | 187 |
| 2024 August | 166 | 54 | 220 |
| 2024 July | 234 | 35 | 269 |
| 2024 June | 187 | 41 | 228 |
| 2024 May | 197 | 29 | 226 |
| 2024 April | 150 | 24 | 174 |
| 2024 March | 167 | 44 | 211 |
| 2024 February | 181 | 47 | 228 |
| 2024 January | 160 | 24 | 184 |
| 2023 December | 138 | 31 | 169 |
| 2023 November | 136 | 34 | 170 |
| 2023 October | 151 | 34 | 185 |
| 2023 September | 127 | 34 | 161 |
| 2023 August | 132 | 10 | 142 |
| 2023 July | 136 | 46 | 182 |
| 2023 June | 155 | 23 | 178 |
| 2023 May | 141 | 26 | 167 |
| 2023 April | 92 | 10 | 102 |
| 2023 March | 144 | 30 | 174 |
| 2023 February | 101 | 27 | 128 |
| 2023 January | 116 | 22 | 138 |
| 2022 December | 99 | 32 | 131 |
| 2022 November | 78 | 22 | 100 |
| 2022 October | 130 | 25 | 155 |
| 2022 September | 103 | 34 | 137 |
| 2022 August | 117 | 46 | 163 |
| 2022 July | 97 | 31 | 128 |
| 2022 June | 92 | 43 | 135 |
| 2022 May | 94 | 44 | 138 |
| 2022 April | 87 | 52 | 139 |
| 2022 March | 119 | 48 | 167 |
| 2022 February | 98 | 41 | 139 |
| 2022 January | 131 | 39 | 170 |
| 2021 December | 97 | 40 | 137 |
| 2021 November | 93 | 49 | 142 |
| 2021 October | 140 | 44 | 184 |
| 2021 September | 96 | 38 | 134 |
| 2021 August | 88 | 35 | 123 |
| 2021 July | 85 | 28 | 113 |
| 2021 June | 100 | 35 | 135 |
| 2021 May | 88 | 35 | 123 |
| 2021 April | 190 | 87 | 277 |
| 2021 March | 120 | 29 | 149 |
| 2021 February | 61 | 29 | 90 |
| 2021 January | 49 | 24 | 73 |
| 2020 December | 63 | 24 | 87 |
| 2020 November | 55 | 22 | 77 |
| 2020 October | 59 | 11 | 70 |
| 2020 September | 55 | 22 | 77 |
| 2020 August | 52 | 26 | 78 |
| 2020 July | 41 | 18 | 59 |
| 2020 June | 60 | 23 | 83 |
| 2020 May | 40 | 13 | 53 |
| 2020 April | 30 | 15 | 45 |
| 2020 March | 13 | 11 | 24 |
| 2020 February | 1 | 0 | 1 |
| 2019 January | 2 | 0 | 2 |
| 2018 May | 13 | 1 | 14 |
| 2018 April | 94 | 10 | 104 |
| 2018 March | 116 | 7 | 123 |
| 2018 February | 76 | 2 | 78 |
| 2018 January | 69 | 4 | 73 |
| 2017 December | 74 | 5 | 79 |
| 2017 November | 49 | 6 | 55 |
| 2017 October | 56 | 2 | 58 |
| 2017 September | 55 | 7 | 62 |
| 2017 August | 50 | 6 | 56 |
| 2017 July | 45 | 7 | 52 |
| 2017 June | 70 | 11 | 81 |
| 2017 May | 76 | 12 | 88 |
| 2017 April | 59 | 4 | 63 |
| 2017 March | 69 | 4 | 73 |
| 2017 February | 229 | 8 | 237 |
| 2017 January | 46 | 4 | 50 |
| 2016 December | 125 | 17 | 142 |
| 2016 November | 105 | 6 | 111 |
| 2016 October | 147 | 24 | 171 |
| 2016 September | 217 | 11 | 228 |
| 2016 August | 107 | 6 | 113 |
| 2016 July | 66 | 13 | 79 |
| 2015 December | 2 | 0 | 2 |
| 2015 September | 1 | 0 | 1 |
| 2015 August | 2 | 0 | 2 |
| 2015 July | 28 | 5 | 33 |
| 2015 June | 50 | 8 | 58 |
| 2015 May | 69 | 13 | 82 |
| 2015 April | 70 | 21 | 91 |
| 2015 March | 37 | 13 | 50 |
| 2015 February | 45 | 9 | 54 |
| 2015 January | 74 | 25 | 99 |
| 2014 December | 50 | 17 | 67 |
| 2014 November | 46 | 14 | 60 |
| 2014 October | 49 | 16 | 65 |
| 2014 September | 40 | 12 | 52 |
| 2014 August | 45 | 26 | 71 |
| 2014 July | 48 | 25 | 73 |
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