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Low-Dose Rituximab for Bullous Pemphigoid. Protocol and Single-Center Experience
Baja dosis de rituximab para penfigoide ampolloso. Protocolo y experiencia de un único centro
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"apellidos" => "Jiménez-Cauhé" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn0005" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "González-García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "M." "apellidos" => "Fernández-Guarino" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "M." "apellidos" => "Asunción Ballester" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Internal Medicine, Hospital Universitario Ramón y Cajal, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Dermatology, Hospital Universitario Ramón y Cajal, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Universidad de Alcalá, Alcalá de Henares, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Baja dosis de rituximab para penfigoide ampolloso. Protocolo y experiencia de un único centro" ] ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0015" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 771 "Ancho" => 1333 "Tamanyo" => 117287 ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">1</span></a> Patients with BP have an increased morbidity and mortality resulting mainly from advanced age and underlying disorders, but also from adverse events of the immunosuppressive therapies used for this condition.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">1,2</span></a> Topical and oral corticosteroids are the mainstay treatment for BP.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">1</span></a> Second line treatment includes several non-validated therapies such as tetracyclines, azathioprine, mycophenolate, methotrexate, chlorambucil or dapsone.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">1,2</span></a> This challenging benefit–risk balance leads to a constant search for newer and safer therapies.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Rituximab has been used for the treatment of autoimmune bullous diseases. Standard doses approved for lymphomas (375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> weekly for 4 weeks) and rheumatoid arthritis (RA) (two infusions of 1000<span class="elsevierStyleHsp" style=""></span>mg repeated in 2 weeks) are the most used protocols, and have shown to be effective in pemphigus vulgaris (PV),<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">3,4</span></a> BP,<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">2,5,6</span></a> and other autoimmune bullous diseases.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">7</span></a> A low-dose rituximab protocol of two infusions of 500<span class="elsevierStyleHsp" style=""></span>mg has also been used for PV, showing a good safety profile and therapeutic response.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">3,4</span></a> Thus, we hypothesized this lower dose might be effective also in BP. Herein we report our experience in the treatment of BP with low-dose rituximab.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Patients</span><p id="par0015" class="elsevierStylePara elsevierViewall">This retrospective, single-center case series included patients with BP treated with low-dose rituximab at Hospital Universitario Ramón y Cajal (Madrid, Spain) between September 2019 and April 2020. Diagnosis of BP was established by clinical, histological and immunological criteria, according to the European guidelines.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">1</span></a> All patients had failure for initial control after treatment with conventional therapies for a minimum of 4 weeks, as defined by the International Pemphigoid Committee.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">8</span></a> Treatment with low-dose rituximab was approved by our institution as an off-label compassionate use.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Pretreatment workup</span><p id="par0020" class="elsevierStylePara elsevierViewall">Pretreatment workup included a complete blood test, chest X-ray, Mantoux test, and several microbiological studies to rule out viral infections including Hepatitis B virus, Hepatitis C virus, and HIV.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Treatment protocol</span><p id="par0025" class="elsevierStylePara elsevierViewall">Patients were premedicated with methylprednisolone 125<span class="elsevierStyleHsp" style=""></span>mg, dexchlorpheniramine 5<span class="elsevierStyleHsp" style=""></span>mg, and paracetamol 1<span class="elsevierStyleHsp" style=""></span>g intravenously the day of the infusion and the day after. A single cycle of two infusions of rituximab 500<span class="elsevierStyleHsp" style=""></span>mg was administered with an interval of 14 days. Vitals and immediate adverse effects were monitored during infusion and the day after.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Follow-up and end points</span><p id="par0030" class="elsevierStylePara elsevierViewall">Frequency of follow-up visits and laboratory investigations were performed considering individual patients’ general condition. End points and outcome measures were defined according to the International Pemphigoid Committee<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">8</span></a> as (a) “Disease control”: time at which new lesions or pruritus cease to form and established lesions begin to heal; (b) “End of consolidation phase”: time at which no new lesions or pruritus have developed for a minimum of 2 weeks and the majority (approximately 80%) of established lesions has healed; (c) “Complete remission during tapering”: absence of nontransient lesions while the patient is receiving more than minimal therapy; (d) “Complete remission”: absence of new or established lesions or pruritus for at least 2 months while the patient is off all BP therapy (CR OFF) or with minimal therapy (CR ON); (e) “Partial remission”: presence of transient new lesions that heal within 1 week for at least 2 months while the patient is off all BP therapy (PR OFF) or with minimal therapy (PR ON). “Minimal therapy” is defined as less than or equal to 0.1<span class="elsevierStyleHsp" style=""></span>mg/kg/day of prednisone (or the equivalent) or 20<span class="elsevierStyleHsp" style=""></span>g/week of clobetasol propionate and/or minimal adjuvant therapy (methotrexate 5<span class="elsevierStyleHsp" style=""></span>mg/week; azathioprine 0.7<span class="elsevierStyleHsp" style=""></span>mg/kg/day; mycophenolate mofetil 500<span class="elsevierStyleHsp" style=""></span>mg/day; or dapsone 50<span class="elsevierStyleHsp" style=""></span>mg/day).</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">Five male and one female patients with a mean age of 78.6 years (range 65–89) were included. Their mean Charlson comorbidity index was 5.6 (range 3–9). The mean history of BP before rituximab treatment was 6.7 months (range 2–16), and it was associated with Alzheimer's disease in two patients and dipeptidyl peptidase-4 (DPP-4) inhibitors intake in one patient. Prior to rituximab, all patients had received conventional systemic therapy including prednisone (six patients), doxycycline (four patients) or azathioprine (three patients), in addition to clobetasol propionate cream 0.05% (six patients). The patients were followed-up for a mean of 52 weeks (range 6–77). <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> show patients’ characteristics and end points, respectively.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Early end points</span><p id="par0040" class="elsevierStylePara elsevierViewall">We observed a rapid and marked response after the two infusions of rituximab (probably influenced also by the premedication with methylprednisolone) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The mean time to disease control was 1.9 weeks (range 1–3), and the mean time to end of consolidation phase was 4 weeks (range 3–5).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Late end points</span><p id="par0045" class="elsevierStylePara elsevierViewall">After a single cycle of low-dose rituximab, four patients (80%) achieved a late end point at a mean of 15.75 weeks (range 13–20), which was maintained at the time of writing this article, for a mean of 28.75 weeks (range 16–38). Three patients achieved partial remission: two with no need of any medication (PR OFF), and one with minimal therapy (PR ON) (prednisone 5<span class="elsevierStyleHsp" style=""></span>mg plus clobetasol propionate cream 0.05%, and clobetasol propionate cream 0.05% alone, respectively). One patient achieved complete remission with no therapy (CR OFF). One patient has 6 weeks of follow-up.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The remaining patient achieved disease control at 1 week, but relapsed 4 weeks after the rituximab treatment. However, he remains in complete remission during tapering with more than minimal adjuvant therapy (CR adj) (prednisone 10<span class="elsevierStyleHsp" style=""></span>mg/day and azathioprine 50<span class="elsevierStyleHsp" style=""></span>mg/day).</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Adverse events</span><p id="par0055" class="elsevierStylePara elsevierViewall">One patient presented with oral erosions and vesicles 2 months after rituximab treatment. It was diagnosed with herpetic gingivostomatitis (confirmed by PCR) and resolved with oral valacyclovir. Another patient who had a claw hand secondary to a stroke developed a pressure ulcer requiring a finger amputation 1.5 months after rituximab treatment, yet a direct link with rituximab is unlikely. No other serious adverse events occurred during the follow-up.</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">Rituximab is a humanized chimeric monoclonal antibody directed against CD-20 antigen on B lymphocytes, with several approved and off-label indications. It has been recently approved by the US Food and Drug Administration (FDA) in 2018, and the European Medicines Agency (EMA) in 2019 as a treatment for PV. Since then, there are increasing articles reporting the treatment of BP with rituximab at standard doses (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">2,5,6</span></a> Lymphoma protocol is more commonly used than RA protocol, although one study found no difference in the efficacy between them.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">6</span></a> At these standard doses, complete remission ranged between 35%<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">2</span></a> and 85%<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a> of the patients, and partial remission between 15%<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a> and 40%.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">2</span></a> These studies reported serious adverse events, mainly infectious, and even cases of deaths. Overall, data suggest that rituximab at standard doses is effective in BP, and also useful as an steroid- and immunosuppressant-sparing therapy but may have serious adverse effects.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">2,5,6</span></a> In addition, a recently published study has shown that mortality in patients with BP treated with rituximab is lower than in those receiving standard treatment.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">9</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Low-dose rituximab has been reported to be effective in a myriad of autoimmune diseases, such as myasthenia gravis, rheumatoid arthritis or immune thrombocytopenia.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">10</span></a> In Dermatology, low-dose rituximab has been mainly used in PV, with satisfactory data in effectiveness and safety.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">3,4</span></a> A meta-analysis by Wang et al. found no difference between standard doses and low-dose in time to disease control, complete remission rate and relapse rate in patients with PV.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">11</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In our study, we present six patients with BP treated with low-dose rituximab (two infusions of 500<span class="elsevierStyleHsp" style=""></span>mg), which is 39% of the dose used in hematology and 50% of the dose used in rheumatology, with an acceptable effectiveness and safety profile. The administration of high doses of methylprednisolone has probably produced this rapid beneficial effect as observed in other diseases,<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">12</span></a> but good long-term control of the disease is derived from the use of rituximab. Only 1 patient of our series experienced a mild adverse event, compared to several serious adverse events with standard doses.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">2,5,6</span></a> CR (including off therapy, minimal therapy and more than minimal therapy) was achieved in 40% of the patients (compared to 35<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">2</span></a>–85%<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a> with standard doses), and PR in 60% of the patients (compared to 15<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a>–40%<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">2</span></a> with standard doses) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Only 1 patient relapsed and had to continue with immunosuppressive therapy, supporting that low-dose rituximab is also useful to avoid steroids and immunosuppressants, decreasing the morbidity and adverse events in advanced age BP patients.</p><p id="par0075" class="elsevierStylePara elsevierViewall">We highlight that these are dependent patients, with high comorbidity and polymedication, leading to a low adherence to first-line treatment (high-potency topical corticosteroids). The aim of this treatment is to improve the quality of life of the patients, reducing their needed care without increasing side effects.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Our study had several limitations, including its retrospective nature, small sample size and a short follow-up period that does not allow to see the effects in the very long term. However, to our knowledge this is the first series of BP treated with low-dose rituximab and it will be useful for future prospective studies.</p><p id="par0085" class="elsevierStylePara elsevierViewall">In conclusion, low-dose rituximab for the treatment of BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. Although future studies are needed, this pilot study suggests that low-dose rituximab could be a therapeutic option for BP.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Funding sources</span><p id="par0090" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1828757" "titulo" => "Graphical abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:3 [ "identificador" => "xres1828755" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0030" "titulo" => "Conclusions" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1594436" "titulo" => "Keywords" ] 3 => array:3 [ "identificador" => "xres1828756" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0035" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0040" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0045" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0050" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0055" "titulo" => "Conclusiones" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1594435" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 6 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Pretreatment workup" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Treatment protocol" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Follow-up and end points" ] ] ] 7 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Early end points" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Late end points" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Adverse events" ] ] ] 8 => array:2 [ "identificador" => "sec0055" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0060" "titulo" => "Funding sources" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-08-11" "fechaAceptado" => "2021-10-14" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1594436" "palabras" => array:3 [ 0 => "Bullous pemphigoid" 1 => "Rituximab" 2 => "Interdisciplinary" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1594435" "palabras" => array:3 [ 0 => "Penfigoide ampolloso" 1 => "Rituximab" 2 => "Interdisciplinar" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Background</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Low-dose rituximab is a protocol used in several autoimmune diseases, that has also shown to be effective and safe in pemphigus vulgaris.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Objectives</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">To study whether low-dose rituximab is also effective for bullous pemphigoid.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Methods</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Patients with BP were treated with a single cycle of two infusions of rituximab 500<span class="elsevierStyleHsp" style=""></span>mg at an interval of 2 weeks. Early and late end points were monitored.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Results</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Six patients, five males and a female, with a mean age of 78.6 years (range 65–89) and a mean history of BP of 6.7 months (range 2–16) were included. A rapid and marked response was observed after a single cycle of treatment, with a mean time to disease control and to end of consolidation phase of 1.9 (range 1–3), and 4 weeks (range 3–5), respectively. Four patients achieved a late end point at a mean of 15.75 weeks (range 13–20). Three of them achieved partial remission with no therapy (two patients) or with minimal therapy (one patient), and one of them achieved complete remission with no therapy. One patient has 6 weeks of clinical follow-up after rituximab administration. The remaining patient relapsed 4 weeks after the rituximab treatment, and remains in complete remission with more than minimal therapy. One patient had a herpetic gingivostomatitis related to rituximab.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclusions</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Low-dose rituximab for BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. This pilot study suggests that low-dose rituximab could be a therapeutic option for BP.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0030" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Antecedentes</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La administración de dosis bajas de rituximab es un protocolo utilizado en diversas enfermedades autoinmunes, que ha demostrado también su eficacia y seguridad para el pénfigo vulgar.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Objetivos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Determinar si rituximab a dosis bajas es efectivo para el penfigoide ampolloso (PA).</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Métodos</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se trató a los pacientes con PA con un ciclo único de 2 infusiones de rituximab 500<span class="elsevierStyleHsp" style=""></span>mg con un intervalo de 2 semanas. Se monitorizaron los puntos temprano y final tardío.</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Resultados</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron en el estudio 6 pacientes, 5 varones y una mujer, con una edad media de 78,6 años (rango: 65.89) e historia media de PA de 6,7 meses (rango: 2-16). Se observó una respuesta rápida y acusada tras un ciclo único de tratamiento, con un tiempo medio hasta el control de la enfermedad y el final de la fase de consolidación de 1,9 (rango: 1-3) y 4 semanas (rango: 3-5), respectivamente. Cuatro pacientes lograron un punto final tardío a una media de 15,75 semanas (rango: 13-20). Tres de ellos lograron una remisión parcial sin terapia (2 pacientes) o con terapia mínima (un paciente), logrando uno de ellos la remisión completa sin terapia. A un paciente se le realizó un seguimiento de 6 semanas tras la administración de rituximab. El paciente restante sufrió una recaída transcurridas 4 semanas del tratamiento de rituximab, permaneciendo en remisión completa con terapia mínima. Un paciente manifestó gingivoestomatitis herpética relacionada con rituximab.</p></span> <span id="abst0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclusiones</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">La administración de dosis bajas de rituximab para PA logró tasas de remisión aceptables y reducción de esteroides, con un mejor perfil de seguridad y un menor coste, en comparación con las dosis estándar. Este estudio piloto sugiere que la administración de bajas dosis de rituximab podría ser una opción terapéutica para el PA.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0035" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0040" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0045" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0050" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0055" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">These authors contributed equally to this work.</p>" "identificador" => "fn0005" ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1375 "Ancho" => 2091 "Tamanyo" => 152085 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Disease phases and end points after rituximab treatment. Each bar represents a patient and its length shows the duration of follow-up. After a single cycle of low-dose rituximab (at week 0), the time to disease control (blue), the time to end of consolidation (red), the time to late end point (yellow) and its duration (green) are shown. One patient had a relapse (black line), requiring retreatment with more than minimal adjuvant therapy (light blue).</p> <p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">CR adj: complete remission with more than minimal adjuvant therapy (also referred to “complete remission during tapering”); CR OFF: complete remission off all therapy; CR ON: complete remission with minimal therapy; PR OFF: partial remission off all therapy; PR ON: partial remission with minimal therapy.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1172 "Ancho" => 1255 "Tamanyo" => 292038 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Clinical picture of patient 4 the day of the first infusion of rituximab 500<span class="elsevierStyleHsp" style=""></span>mg (A) and the day of the second infusion after 2 weeks (B).</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">AZA, azathioprine; CLOB, clobetasol propionate cream 0.05%; CR OFF, complete remission off all therapy; DOXY, doxycycline; GDS: global deterioration scale; PRED: prednisone; PR OFF, partial remission off all therapy; PR ON, partial remission with minimal therapy.</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" style="border-bottom: 2px solid black">Patient \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">Sex/age (years) \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">History of the disease (months) \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">Associated conditions \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">Previous therapies \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">Adverse events of rituximab \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">Disease control at week \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">Late end point (at week) \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">Minimal therapy \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">Relapse at week \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">Follow-up (weeks) \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">1 \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">M/82 \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">7 \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">Gliptin intake \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">AZA (50 mg), PRED (30 mg), CLOB \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">– \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">2 \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">PR OFF (13) \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">– \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">– \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">54 \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">2 \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">M/65 \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">16 \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">– \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">AZA (75 mg/day), DOXY (100 mg/day), PRED (20 mg/day), CLOB \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">Herpetic gingiva-stomatitis \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">2 \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">PR ON (17) \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">PRED 5<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>CLOB \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">– \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">69 \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">3 \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">M/81 \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">2.5 \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">– \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">PRED (30 mg/day), DOXY (100 mg/day) \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">– \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">1 \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">– \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">– \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">4 \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">77 \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">4 \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">M/89 \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">6 \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">Alzheimer (GDS<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4) \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">PRED (20<span class="elsevierStyleHsp" style=""></span>mg/day), DOXY (100 mg/day), CLOB \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">– \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">1 \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">CR OFF (20) \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">– \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">– \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">74 \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">5 \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">M/77 \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">2 \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">Alzheimer (GDS<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6) \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">PRED (30 mg/day), CLOB \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">– \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">3 \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">PR OFF (19) \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">– \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">32 \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">6 \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">F/77 \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">6 \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">– \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">PRED (20 mg/day),CLOB \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">– \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">2 \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">– \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">CLOB \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">– \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">6 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Demographic, clinical characteristics and outcomes of patients with bullous pemphigoid treated with low-dose rituximab.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">CR adj, complete remission with more than minimal adjuvant therapy; CR OF, complete remission off all therapy; CR ON, complete remission with minimal therapy; PR adj, partial remission with more than minimal therapy; PR OFF, partial remission off all therapy; PR ON, partial remission with minimal therapy. Lymphoma protocol (375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> weekly for 4 weeks); RA: rheumatoid arthritis protocol (two infusions of 1000<span class="elsevierStyleHsp" style=""></span>mg repeated in 2 weeks); RTX: rituximab.</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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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">Current study, <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5 \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">Polansky et al., 2019; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20 \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">Kremer et al., 2018; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>62 \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">Tovanabutra et al., 2019; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>21 \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">Dose of RTX \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 doses of 500<span class="elsevierStyleHsp" style=""></span>mg (low-dose RTX) \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">1: Lymphoma19: RA \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">33: Lymphoma27: RA2: other \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">14: Lymphoma7: RA \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">Complete remission, <span class="elsevierStyleItalic">n</span> (%) \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 (40%)- CR OFF: 1 (20%)- CR adj: 1 (20%) \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">7 (35%)- CR OFF: 2 (10%)- CR ON: 4 (20%)- CR adj: 1 (5%) \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">52 (85%)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>- CR OFF or ON: 40 (65%)- CR adj: 12 (20%) \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">12 (57%)- CR OFF: 2 (9.5%)- CR ON: 10 (47.6%) \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">Partial remission, <span class="elsevierStyleItalic">n</span> (%) \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 (60%)- PR OFF: 2 (40%)- PR ON: 1 (20%) \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">8 (40%)- PR OFF: 1 (5%)- PR ON: 3 (15%)- PR adj: 4 (20%) \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">9 (15%)Not specified \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">4 (19%)- PR OFF: 1 (4.7%)- PR ON: 3 (14.3%) \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">Time to remission, mean (range); months \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">3.67 (3–4.7) \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">5.6 (1.9–13.9) \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">– \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">– \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">Relapse, <span class="elsevierStyleItalic">n</span> (%) \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">1 (20%) \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 (13.3%) \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">15 (24.5%) \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">16 (76.2%) \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">Time from RTX to relapse, mean (range); months \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">1 \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">11.8 (10.9–12.6) (from first dose of RTX) \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">10.2 (1–24) (from last dose of RTX) \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">– \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">Follow-up period, mean (range); months \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">11.2 (6.8–14.2) \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">16.9 (4.4–41.6) \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">33 (3–108) \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">44.5 (3.7–101.5) \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">Adverse effects \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">1 patient (20%),Mild \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">23 events- 15 hospitalizations- 0 deaths \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">13 patients (24%)- 2 deaths \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">4 patients (19%)-1 death \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">This study classified as CR OFF patients who were off therapy or treated with prednisone with a maximal dose of 10<span class="elsevierStyleHsp" style=""></span>mg. Since the latter group is better defined as CR ON, this group is expressed in the table as CR OFF or ON. Also this study classified CR ON as patients with more than prednisone 10<span class="elsevierStyleHsp" style=""></span>mg and/or other systemic therapies. This group is expressed in the table as CR adj.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Comparison of outcomes between treatment of BP with low-dose rituximab (current study) and standard doses.</p>" ] ] 4 => array:5 [ "identificador" => "fig0015" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 771 "Ancho" => 1333 "Tamanyo" => 117287 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:12 [ 0 => array:3 [ "identificador" => "bib0065" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of bullous pemphigoid: the European Dermatology Forum consensus in collaboration with the European Academy of Dermatology and Venereology" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 14 | 12 | 26 |
| 2024 October | 119 | 76 | 195 |
| 2024 September | 156 | 80 | 236 |
| 2024 August | 195 | 84 | 279 |
| 2024 July | 198 | 83 | 281 |
| 2024 June | 163 | 72 | 235 |
| 2024 May | 164 | 71 | 235 |
| 2024 April | 117 | 43 | 160 |
| 2024 March | 138 | 55 | 193 |
| 2024 February | 119 | 55 | 174 |
| 2024 January | 173 | 52 | 225 |
| 2023 December | 185 | 24 | 209 |
| 2023 November | 159 | 53 | 212 |
| 2023 October | 174 | 45 | 219 |
| 2023 September | 142 | 44 | 186 |
| 2023 August | 94 | 30 | 124 |
| 2023 July | 124 | 49 | 173 |
| 2023 June | 146 | 35 | 181 |
| 2023 May | 119 | 40 | 159 |
| 2023 April | 101 | 38 | 139 |
| 2023 March | 153 | 43 | 196 |
| 2023 February | 137 | 32 | 169 |
| 2023 January | 190 | 85 | 275 |
| 2022 December | 126 | 47 | 173 |
| 2022 November | 199 | 49 | 248 |
| 2022 October | 151 | 28 | 179 |
| 2022 September | 146 | 56 | 202 |
| 2022 August | 107 | 63 | 170 |
| 2022 July | 172 | 65 | 237 |
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