Letter to the Editor
Fingolimod-induced remission in a patient with ulcerative colitis and multiple sclerosis
Remisión inducida por fingolimod en una paciente con colitis ulcerosa y esclerosis múltiple
Pablo Ladrón Abiaa,
, Carmen Alcalá Vicenteb, Sara Martínez Delgadoa, Guillermo Bastida Paza,c
Corresponding author
a Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Medicina Digestiva, Hospital Universitario y Politécnico La Fe, Valencia, Spain
b Unidad de Neuroinmunología, Servicio de Neurología, Hospital Universitario y Politécnico La Fe, Valencia, Spain
c Instituto de Investigación Sanitaria La Fe, Valencia, Spain
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class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Fingolimod-induced remission in a patient with ulcerative colitis and multiple sclerosis" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "156" "paginaFinal" => "157" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Pablo Ladrón Abia, Carmen Alcalá Vicente, Sara Martínez Delgado, Guillermo Bastida Paz" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Pablo" "apellidos" => "Ladrón Abia" "email" => array:1 [ 0 => "paul199340@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Carmen" "apellidos" => "Alcalá Vicente" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Sara" "apellidos" => "Martínez Delgado" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Guillermo" "apellidos" => "Bastida Paz" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Medicina Digestiva, Hospital Universitario y Politécnico La Fe, Valencia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Neuroinmunología, Servicio de Neurología, Hospital Universitario y Politécnico La Fe, Valencia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Instituto de Investigación Sanitaria La Fe, Valencia, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Remisión inducida por fingolimod en una paciente con colitis ulcerosa y esclerosis múltiple" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 865 "Ancho" => 1750 "Tamanyo" => 101356 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Brain MRI: hyper-uptake of contrast in finger-like periventricular lesions in FLAIR sequence. The image on the left corresponds to the MRI at diagnosis (October 2017) and the image on the right to the follow-up MRI (June 2018), with no sign of new demyelinating lesions.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Ulcerative colitis (UC) is a chronic bowel disease with an intermittent course characterised by continuous inflammation of the mucosa which, to varying extents, affects the rectum and the rest of the colon. Although there is a broad range of therapies available, it is not possible to keep the inflammatory activity in remission in some patients. Anti-TNFα drugs are one of the most effective and widely used treatments in cases of moderate/severe activity. Opportunistic infections are one of the main side effects of this therapy. Another less common adverse effect is the development of demyelinating disease due to nervous system involvement.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">With this in mind, we present the case of a 56-year-old female patient, diagnosed with pan-ulcerative colitis at the age of 44 after presenting with a severe steroid-refractory flare-up which required rescue ciclosporin and 6-mercaptopurine (6-MP) for maintenance. A few months later, she had a further severe flare-up, requiring infliximab (anti-TNFα)) 5<span class="elsevierStyleHsp" style=""></span>mg/kg weeks 0, 2 and 6, with subsequent escalation to 5<span class="elsevierStyleHsp" style=""></span>mg/kg every four weeks due to severe endoscopic activity. After one year of treatment with clinical remission the infliximab was discontinued, maintaining 6-MP, but this was then stopped due to recurrent urinary tract infections and leukopenia. For the next four years she was treated with oral mesalazine 2<span class="elsevierStyleHsp" style=""></span>g/day, with a good response. The infliximab then had to be restarted at 5<span class="elsevierStyleHsp" style=""></span>mg/kg in weeks 0, 2 and 6, due to moderate-to-severe clinical exacerbation. However, after the induction, she had a severe infusion reaction to infliximab, and was switched to adalimumab (anti-TNFα) 40<span class="elsevierStyleHsp" style=""></span>mg SC every two weeks for maintenance. This did not achieve an adequate clinical response, despite adding granulocytapheresis and tacrolimus suppositories.</p><p id="par0015" class="elsevierStylePara elsevierViewall">In the absence of response, the patient was started on vedolizumab (anti-integrin α4β7) 300<span class="elsevierStyleHsp" style=""></span>mg IV every eight weeks, with subsequent escalation to every four weeks. However, her UC remained chronically active with elevated levels of faecal calprotectin. Surgical treatment was then considered, but after being rejected by the patient, it was decided to start golimumab (anti-TNFα) 200/100<span class="elsevierStyleHsp" style=""></span>mg weeks 0 and 2, escalating to 100<span class="elsevierStyleHsp" style=""></span>mg SC every two weeks for maintenance due to partial response after the induction.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Nine months after starting the treatment, the patient developed dysaesthesia in her lower limbs. Brain MRI revealed lesions with a demyelinating profile, typical of multiple sclerosis (MS), in the corpus callosum and periventricular and juxtacortical areas. The differential diagnosis was between multiple sclerosis (MS), neuromyelitis optica and acute disseminated encephalomyelitis. The diagnosis of MS was established due to the presence of intrathecal oligoclonal bands (a finding seen in 80% of MS) and the typical brain lesions of this disease.</p><p id="par0025" class="elsevierStylePara elsevierViewall">As golimumab was the only treatment the patient was taking, in view of the reported association between anti-TNFα and MS,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a> the trigger for the MS was assumed to be golimumab. This adverse event was unrelated to the dose used.</p><p id="par0030" class="elsevierStylePara elsevierViewall">As the patient was found to be positive for anti-John Cunningham virus antibodies, natalizumab was not administered, but she was given oral fingolimod (S1P receptor modulator) 0.5<span class="elsevierStyleHsp" style=""></span>mg/day and boluses of 6-methylprednisolone 1<span class="elsevierStyleHsp" style=""></span>g per day orally for three days, with excellent response. The follow-up MRI one year after diagnosis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) showed the demyelinating lesions to be stable.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Interestingly, from the point of view of her UC, after failure of various different lines of medical treatment, 12 weeks after starting fingolimod the patient had a complete clinical and endoscopic response. She has now been on fingolimod for over three years.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The pathogenesis of MS with anti-TNFα therapy is still not fully understood.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,3</span></a> New drugs are emerging for UC, including S1P receptor modulator drugs (fingolimod, approved for MS and ozanimod, second generation).<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> The blockade of the S1P receptor leads to the sequestration of lymphocytes in the peripheral lymphoid organs, which hinders their transit to the areas of inflammation. These drugs could be effective in the management of UC and MS. Although this is an anecdotal case of strong response to fingolimod, this family of drugs could be an option for compassionate use in patients with chronic activity refractory to current pharmacological treatments, whose only option is surgery.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts 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: Ladrón Abia P, Alcalá Vicente C, Martínez Delgado S, Bastida Paz G. Remisión inducida por fingolimod en una paciente con colitis ulcerosa y esclerosis múltiple. Gastroenterol Hepatol. 2021;44:156–157.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 865 "Ancho" => 1750 "Tamanyo" => 101356 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Brain MRI: hyper-uptake of contrast in finger-like periventricular lesions in FLAIR sequence. The image on the left corresponds to the MRI at diagnosis (October 2017) and the image on the right to the follow-up MRI (June 2018), with no sign of new demyelinating lesions.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CNS Demyelination with TNF-α Blockers" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E. Kemanetzoglou" 1 => "E. 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Drosos" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Autoimmun Rev" "fecha" => "2014" "volumen" => "13" "paginaInicial" => "54" "paginaFinal" => "58" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sphingosine-1-phosphate receptor: a novel therapeutic target in ulcerative colitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R. Izzo" 1 => "M.M. Figliuzzi" 2 => "G. Monteleone" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/1744666X.2016.1217774" "Revista" => array:6 [ "tituloSerie" => "Expert Rev Clin Immunol" "fecha" => "2016" "volumen" => "12" "paginaInicial" => "1137" "paginaFinal" => "1139" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27494562" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/24443824/0000004400000002/v1_202102270718/S2444382421000298/v1_202102270718/en/main.assets" "Apartado" => array:4 [ "identificador" => "48445" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letter to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/24443824/0000004400000002/v1_202102270718/S2444382421000298/v1_202102270718/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444382421000298?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 30 | 4 | 34 |
| 2024 September | 75 | 4 | 79 |
| 2024 August | 64 | 5 | 69 |
| 2024 July | 35 | 4 | 39 |
| 2024 June | 28 | 9 | 37 |
| 2024 May | 25 | 5 | 30 |
| 2024 April | 43 | 7 | 50 |
| 2024 March | 39 | 4 | 43 |
| 2024 February | 35 | 4 | 39 |
| 2024 January | 51 | 2 | 53 |
| 2023 December | 76 | 9 | 85 |
| 2023 November | 74 | 11 | 85 |
| 2023 October | 87 | 8 | 95 |
| 2023 September | 49 | 6 | 55 |
| 2023 August | 50 | 2 | 52 |
| 2023 July | 21 | 3 | 24 |
| 2023 June | 38 | 2 | 40 |
| 2023 May | 40 | 0 | 40 |
| 2023 April | 39 | 2 | 41 |
| 2023 March | 16 | 8 | 24 |
| 2023 February | 13 | 2 | 15 |
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