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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Pyoderma gangrenosum &#40;PG&#41; is an uncommon inflammatory skin disorder characterized by chronic and recurrent blistered or necrotic ulcers&#44; and a predominantly neutrophilic infiltrate on histopathology&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Several subtypes of PG exist such as ulcerative&#44; bullous&#44; pustular&#44; peristomal and superficial granulomatous&#44; yet the ulcerative variant represents about 85&#37; of cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;2</span></a> The etiology of this debilitating disease is not fully understood&#46; PG can be idiopathic&#44; or be associated with drug consumption &#40;cocaine&#47;levamisole&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> inflammatory bowel disease &#40;IBD&#41;&#44; rheumatoid arthritis &#40;RA&#41;&#44; hematologic disorders&#44; or be part of an inherited inflammatory syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> The pathogenesis of PG has not yet been completely defined and currently no drugs have been approved for the management of this disease&#46; In most cases&#44; management is based on off-label classical immunosuppressors and biological agents&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Recent studies have demonstrate that the Janus kinase &#40;JAK&#41; pathway may be involved in the progression of PG&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4&#44;5</span></a> Off-label treatment with JAK inhibitors has been proposed by some authors<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6&#8211;10</span></a> as an optimal therapeutic strategy for the management of refractory PG in patients in whom other systemic therapies have failed&#46; Experience with tofacitinib<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5&#8211;9</span></a> has been the most widely reported to this date&#59; however&#44; the use of more-selective JAK inhibitors such as upadacitinib could be also effective with a better safety profile and&#44; indeed&#44; a few cases have already been published&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We conducted a retrospective bi-centric case-series evaluating short-term safety and efficacy profile of upadacitinib 15<span class="elsevierStyleHsp" style=""></span>mg&#47;daily or 30<span class="elsevierStyleHsp" style=""></span>mg&#47;daily for the management of refractory PG&#46; Clinical response was assessed by Physician Global Assessment &#40;PGA&#41; during the evaluated period&#46; An optimal response was considered when reaching a PGA &#8804;2&#46; Four cases of recalcitrant PG were included&#46; Two patients were women and two were men&#44; ranging from 26 up to 62 years&#46; The mean baseline PGA was 4 &#40;ranging from 0 to 4&#41;&#46; The mean course of PG prior to upadacitinib treatment was 4&#46;3 years &#40;range&#44; 1&#8211;10&#41;&#46; A well-known trigger or comorbidity were identified in all patients&#46; One patient had poorly-controlled inflammatory bowel disease and a different participant&#44; well-controlled rheumatoid arthritis&#46; In the last two patients the PG onset was associated with the use of levamisole-adulterated-cocaine in one case and breast surgery in the other one&#46; Two patients had ulcerative PG limited to the lower legs&#44; one patient had generalized pustular PG and the other one&#44; the generalized vegetative subtype&#46; Prior to upadacitinib treatment&#44; a mean 5 &#40;range&#44; 4&#8211;6&#41; systemic therapies had failed in all patients&#46; Three patients were on concomitant systemic treatments during upadacitinib initiation&#59; however&#44; they had been on these additional drugs for a significant amount of time without improvement&#44; prior to starting upadacitinib&#46; Systemic corticosteroids could be down titrated or completely removed after upadacitinib introduction in the entire cohort&#46; All patients reached a PGA &#8804;2 after a mean follow-up of 17&#46;5 weeks &#40;range&#44; 12&#8211;26&#41;&#44; controlling pain and without developing drug-related severe adverse events or miss-controlling PG-related comorbidities&#46; Baseline characteristics&#44; comorbidities&#44; prior and concomitant therapies are illustrated in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Clinical response to upadacitinib in patients &#35;2 and &#35;3 can be seen in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">While this is a small case-series with a short follow-up based on our own observations&#44; and according to Kooybaran et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> upadacitinib seems to be a promising therapeutic alternative and possible corticosteroid sparing option for patients with either pustular&#44; vegetative or classic PG with failed multiple systemic therapies &#40;combined or in monotherapy&#41; as previously reported for tofacitinib&#46; Nonetheless&#44; the drug safety profile could be better&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Currently&#44; no therapies have been approved by the EMA or the FDA for the management of PG&#59; therefore upadacitinib and other JAK-inhibitors<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5&#8211;10</span></a> could be considered a reasonable alternative &#40;combined or in monotherapy&#41; especially for patients with inflammatory bowel disease or rheumatoid arthritis&#46; However&#44; future clinical trials and long-term real-world series will be needed to evaluate the efficacy profile of upadacitinib and other JAK inhibitors in the management of refractory PG&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0020" class="elsevierStylePara elsevierViewall">This research received no specific grant from any funding agency in the public or private sector&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Informed consent</span><p id="par0025" class="elsevierStylePara elsevierViewall">All informed consents are available&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0030" class="elsevierStylePara elsevierViewall">Pedro Mercader-Garc&#237;a declared having received speaker fees and compensation for being a member of advisory boards from Sanofi&#44; Leo Pharma&#44; Lilly and Abbvie&#44; outside the submitted work&#46; The remaining authors declared no conflicts of interest whatsoever&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Data availability</span><p id="par0035" class="elsevierStylePara elsevierViewall">All data are available on request from the authors&#46;</p></span></span>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age &#40;years&#41; and gender&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">Age of the PG<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&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">Cardiovascular risk factors&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">Smoker&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">PG associated comorbidities or trigger factors&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">Prior systemic treatments&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">Upadacitinib dose&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">Concomitant therapies&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">Basal PGA<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;0&#8211;4&#41;&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">Weeks of follow-up &#40;number&#41;&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">Final PGA &#40;0&#8211;4&#41;&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">Case 1Vegetative&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">45&#44; male&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">1 year&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">No&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">No&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">Inflammatory bowel disease&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">Scs<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>MethotrexateCyclosporinAdalimumab&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">15<span class="elsevierStyleHsp" style=""></span>mg daily&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">Adalimumab 40<span class="elsevierStyleHsp" style=""></span>mg&#47;weeklyScs 20<span class="elsevierStyleHsp" style=""></span>mg&#47;daily&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&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">Case 2Pustular&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">26&#44; female&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">1 year&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">No&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">No&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">Mammoplasty&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">ScsMethotrexateCyclosporinAdalimumab&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">15<span class="elsevierStyleHsp" style=""></span>mg daily first month&#44; and then 30<span class="elsevierStyleHsp" style=""></span>mg&#47;daily&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">Adalimumab 40<span class="elsevierStyleHsp" style=""></span>mg&#47;weeklyScs 20<span class="elsevierStyleHsp" style=""></span>mg&#47;daily&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&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">Case 3Ulcerative&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">62&#44; female&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 years&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">Dyslipidemia&#44; diabetes&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">Yes&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">Rheumatoid arthritis&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">ScsMethotrexateCyclosporinAdalimumabGolimumab&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">30<span class="elsevierStyleHsp" style=""></span>mg&#47;daily&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">Scs 75<span class="elsevierStyleHsp" style=""></span>mg&#47;daily&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&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">Case 4Ulcerative&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">50&#44; male&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">10 years&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">Arterial hypertension&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">Yes&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">Cocaine abuse&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">ScsMethotrexateAzathioprineCyclosporinAdalimumabCertolizumabInfliximab&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">30<span class="elsevierStyleHsp" style=""></span>mg&#47;daily&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">No&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab3643136.png"
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              "identificador" => "tblfn0005"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Summary of our cases of PG treated with upadacitinib &#40;including treatment regimens&#41;&#46;</p>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:10 [
            0 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pyoderma gangrenosum &#8211; a guide to diagnosis and management"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "C&#46; George"
                            1 => "F&#46; Deroide"
                            2 => "M&#46; Rustin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.7861/clinmedicine.19-3-224"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Med &#40;Lond&#41;"
                        "fecha" => "2019"
                        "volumen" => "19"
                        "paginaInicial" => "224"
                        "paginaFinal" => "228"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31092515"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            1 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pyoderma gangrenosum&#58; a review of pathogenesis and treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "C&#46; Ahn"
                            1 => "D&#46; Negus"
                            2 => "W&#46; Huang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/1744666X.2018.1438269"
                      "Revista" => array:6 [
                        "tituloSerie" => "Expert Rev Clin Immunol"
                        "fecha" => "2018"
                        "volumen" => "14"
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Case and Research Letter
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Available online 4 September 2024
Four-case Report of Upadacitinib as an Alternative Treatment for Patients With Recalcitrant Pyoderma Gangrenosum
Upadacitinib como alternativa terapéutica en pacientes con pioderma gangrenoso recalcitrante: reporte de cuatro casos
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F.J. Melgosa Ramosa,
Corresponding author
javimelgo2017@gmail.com

Corresponding author.
, R. García-Ruíza, A. Aguado Vázqueza, P. Mercader-Garcíab
a Department of Dermatology, University Hospital Doctor Peset of Valencia, Valencia, Spain
b Department of Dermatology, University Hospital Morales Meseguer, Murcia, Spain
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F.J. Melgosa Ramos, R. García-Ruíz, A. Aguado Vázquez, P. Mercader-García
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Table 1. Summary of our cases of PG treated with upadacitinib (including treatment regimens).
Full Text
To the Editor,

Pyoderma gangrenosum (PG) is an uncommon inflammatory skin disorder characterized by chronic and recurrent blistered or necrotic ulcers, and a predominantly neutrophilic infiltrate on histopathology.1 Several subtypes of PG exist such as ulcerative, bullous, pustular, peristomal and superficial granulomatous, yet the ulcerative variant represents about 85% of cases.1,2 The etiology of this debilitating disease is not fully understood. PG can be idiopathic, or be associated with drug consumption (cocaine/levamisole),3 inflammatory bowel disease (IBD), rheumatoid arthritis (RA), hematologic disorders, or be part of an inherited inflammatory syndrome.2 The pathogenesis of PG has not yet been completely defined and currently no drugs have been approved for the management of this disease. In most cases, management is based on off-label classical immunosuppressors and biological agents.4 Recent studies have demonstrate that the Janus kinase (JAK) pathway may be involved in the progression of PG.4,5 Off-label treatment with JAK inhibitors has been proposed by some authors6–10 as an optimal therapeutic strategy for the management of refractory PG in patients in whom other systemic therapies have failed. Experience with tofacitinib5–9 has been the most widely reported to this date; however, the use of more-selective JAK inhibitors such as upadacitinib could be also effective with a better safety profile and, indeed, a few cases have already been published.10

We conducted a retrospective bi-centric case-series evaluating short-term safety and efficacy profile of upadacitinib 15mg/daily or 30mg/daily for the management of refractory PG. Clinical response was assessed by Physician Global Assessment (PGA) during the evaluated period. An optimal response was considered when reaching a PGA ≤2. Four cases of recalcitrant PG were included. Two patients were women and two were men, ranging from 26 up to 62 years. The mean baseline PGA was 4 (ranging from 0 to 4). The mean course of PG prior to upadacitinib treatment was 4.3 years (range, 1–10). A well-known trigger or comorbidity were identified in all patients. One patient had poorly-controlled inflammatory bowel disease and a different participant, well-controlled rheumatoid arthritis. In the last two patients the PG onset was associated with the use of levamisole-adulterated-cocaine in one case and breast surgery in the other one. Two patients had ulcerative PG limited to the lower legs, one patient had generalized pustular PG and the other one, the generalized vegetative subtype. Prior to upadacitinib treatment, a mean 5 (range, 4–6) systemic therapies had failed in all patients. Three patients were on concomitant systemic treatments during upadacitinib initiation; however, they had been on these additional drugs for a significant amount of time without improvement, prior to starting upadacitinib. Systemic corticosteroids could be down titrated or completely removed after upadacitinib introduction in the entire cohort. All patients reached a PGA ≤2 after a mean follow-up of 17.5 weeks (range, 12–26), controlling pain and without developing drug-related severe adverse events or miss-controlling PG-related comorbidities. Baseline characteristics, comorbidities, prior and concomitant therapies are illustrated in Table 1. Clinical response to upadacitinib in patients #2 and #3 can be seen in Fig. 1.

Table 1.

Summary of our cases of PG treated with upadacitinib (including treatment regimens).

  Age (years) and gender  Age of the PGa  Cardiovascular risk factors  Smoker  PG associated comorbidities or trigger factors  Prior systemic treatments  Upadacitinib dose  Concomitant therapies  Basal PGAb (0–4)  Weeks of follow-up (number)  Final PGA (0–4) 
Case 1Vegetative  45, male  1 year  No  No  Inflammatory bowel disease  ScscMethotrexateCyclosporinAdalimumab  15mg daily  Adalimumab 40mg/weeklyScs 20mg/daily  26 
Case 2Pustular  26, female  1 year  No  No  Mammoplasty  ScsMethotrexateCyclosporinAdalimumab  15mg daily first month, and then 30mg/daily  Adalimumab 40mg/weeklyScs 20mg/daily  16 
Case 3Ulcerative  62, female  5 years  Dyslipidemia, diabetes  Yes  Rheumatoid arthritis  ScsMethotrexateCyclosporinAdalimumabGolimumab  30mg/daily  Scs 75mg/daily  16 
Case 4Ulcerative  50, male  10 years  Arterial hypertension  Yes  Cocaine abuse  ScsMethotrexateAzathioprineCyclosporinAdalimumabCertolizumabInfliximab  30mg/daily  No  12 
a

Pyoderma gangrenosum.

b

Physician Global Assessment.

c

Systemic corticosteroids.

Figure 1.

Pyoderma gangrenosum treated with upadacitinib: (a) case #2 prior to upadacitinib therapy; (b) case #2, 10 weeks after starting upadacitinib; (c) case #3 prior to upadacitinib; (d) case #3, 4 weeks after starting upadacitinib.

(0.46MB).

While this is a small case-series with a short follow-up based on our own observations, and according to Kooybaran et al.,10 upadacitinib seems to be a promising therapeutic alternative and possible corticosteroid sparing option for patients with either pustular, vegetative or classic PG with failed multiple systemic therapies (combined or in monotherapy) as previously reported for tofacitinib. Nonetheless, the drug safety profile could be better.10 Currently, no therapies have been approved by the EMA or the FDA for the management of PG; therefore upadacitinib and other JAK-inhibitors5–10 could be considered a reasonable alternative (combined or in monotherapy) especially for patients with inflammatory bowel disease or rheumatoid arthritis. However, future clinical trials and long-term real-world series will be needed to evaluate the efficacy profile of upadacitinib and other JAK inhibitors in the management of refractory PG.

Funding

This research received no specific grant from any funding agency in the public or private sector.

Informed consent

All informed consents are available.

Conflicts of interest

Pedro Mercader-García declared having received speaker fees and compensation for being a member of advisory boards from Sanofi, Leo Pharma, Lilly and Abbvie, outside the submitted work. The remaining authors declared no conflicts of interest whatsoever.

Data availability

All data are available on request from the authors.

Acknowledgements

We wish to thank Almudena Mateu Puchades and Mª del Carmen Hidalgo Boronat for data collection support.

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