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reduce side effects&#44; and improve economic efficiency&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1&#44;2</span></a> Below we&#8217;ll be discussing the results of 5 studies of patients with well-controlled AD on dupilumab&#44; in whom the dosing interval was extended beyond the above-mentioned 2-week threshold&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The first study to explore this idea was the randomized LIBERTY AD SOLO-CONTINUE clinical trial&#44; which is a continuation of the trials that led to the approval of dupilumab for the management of AD&#46; It studied a total of 422 patients categorized into 4 groups based on the dosing interval&#58; Q1W&#47;Q2W&#44; Q4W&#44; and Q8W&#46; Thirty-six weeks after down-titration&#44; no significant differences were reported in the percentage change observed in the Eczema Area and Severity Index &#40;EASI&#41;&#44; or in the proportion of patients with Investigator Global Assessment &#40;IGA&#41; 0-1 between the Q1W&#47;Q2W and Q4W groups&#46; Conversely&#44; a proportion of patients with EASI-75 was lost &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;045&#41;&#44; and the number of patients with&#44; at least&#44; a 3-point increase in the pruritus numeric rating scale &#40;P-NRS&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; increased&#46; The Q8W group significantly reduced efficacy in the above-mentioned scales&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Afterwards&#44; a Dutch cohort of 90 patients compared the EASI of the Q2W regimen vs the Q4W and Q6W&#47;Q8W regimens&#46; Down-titration was gradual&#44; first to Q3W&#44; and then for those who maintained responses doses were further spaced out&#46; After an&#44; at least&#44; 6-month follow-up&#44; no significant EASI increases were seen in either Q4W or Q6W&#47;Q8W&#46; While the P-NRS remained stable in the Q4W group&#44; it increased in the Q6W&#47;Q8W group &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46; Despite the reduced drug levels&#44; the severity biomarkers PARC&#47;CCL18 and TARC&#47;CCL17 remained low&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">A French series of 88 patients identified 3 predictors of sustained response after dose reduction&#58; spacing due to good sustained response rather than side effects &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;034&#41;&#44; older age &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41;&#44; and lower monthly dose of topical corticosteroids &#40;0&#46;016&#41;&#46; Data from the reviewed studies are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion&#44; various authors propose a consensual and gradual down-titration of dupilumab in well-controlled patients&#46; It has been hypothesized that the sustained response is due to the selection of super responders&#44; in whom a lower drug level saturates the pharmacological target&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1&#44;2&#44;4&#44;5</span></a> Conducting controlled studies aims to avoid iatrogenesis and promote efficiency with the advent of new drugs&#46;</p></span>"
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                  \t\t\t\t">&#37;EASI-0&#46;06&#44; EASI-75 71&#46;6&#37; vs &#37;EASI-0&#46;06&#44; EASI-75 71&#46;6&#37;&#44; &#37;EASI-3&#46;84 &#40;NS&#41;&#44; EASI-75 58&#46;3&#37; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#44; &#37;EASI-6&#46;84 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#44; EASI-75 54&#46;9&#37; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#44; &#37;EASI-21&#46;6 &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; EASI-75 30&#46;4&#37; &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a>&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">Prospective cohort&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"><span class="elsevierStyleHsp" style=""></span>&#62;18 years&#44; 52 weeks Q2W with DUPI 300&#44; EASI &#60;<span class="elsevierStyleHsp" style=""></span>7 for 6 months&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">EASI and P-NRS after 6 months&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">Q2W Q4W Q8W&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 30 30n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>90&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">EASI 6&#46;4&#44; P-NRS 4&#46;0 vs EASI 1&#46;7&#44; P-NRS 2&#46;0&#44; EASI 2&#46;3&#44; P-NRS 2&#46;0 EASI and P-NRS reached by every group before down-titration&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">EASI 5&#46;4 &#40;NS&#41;&#44; P-NRS 4&#46;0 &#40;NS&#41;&#44; EASI 1&#46;5 &#40;NS&#41;&#44; P-NRS 2&#46;0 &#40;NS&#41;&#44; EASI 2&#46;9 &#40;NS&#41;&#44; P-NRS 3&#46;0 &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a>&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 series&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"><span class="elsevierStyleHsp" style=""></span>&#62;18 years&#44; SCORAD50&#44; down-titration&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">Response persistence &#40;unspecified scale&#41; after 6&#46;3 months&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">Q2W Q4W&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">N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>55<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Data not provided in the original article&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">At the 6&#46;3-month follow-up&#44; 35 individuals maintained&#47;increased spacing&#46; Data not provided by the lead author&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"><a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a>&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 series&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"><span class="elsevierStyleHsp" style=""></span>&#62;18 years&#44; 52 weeks Q2W with DUPI 300&#44; EASI&#8804; 7 and DLQI&#8804; 5 for 6 months&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">EASI&#44; P-NRS&#44; DLQI after 32 weeks&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">Q3W Q4W&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">35 9n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>44<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EASI 0&#46;39&#44; P-NRS 1&#46;04&#44; DLQI 3&#46;28 vs EASI 0&#46;18&#44; P-NRS 1&#46;05&#44; DLQI 3&#46;55EASI&#44; P-NRS and DLQI reached by every group before down-titration&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">EASI 0&#46;45 &#40;NS&#41;&#44; P-NRS 0&#46;94 &#40;NS&#41;&#44; DLQI 3&#46;2 &#40;NS&#41;&#44; EASI 0&#46;22 &#40;NS&#41;&#44; P-NRS 1&#46;14 &#40;NS&#41;&#44; DLQI 2&#46;8 &#40;NS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a>&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 series&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"><span class="elsevierStyleHsp" style=""></span>&#62;18 years&#44; 52 weeks Q2W with DUPI 300&#44; IGA 0-1&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">EASI and IGA after 12 months&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">Q3W Q4W Q2W<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>17&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">IGA 1&#46;00&#44; EASI -16&#46;05 IGA and EASI reached by every group before down-titration&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">IGA 1&#46;42 &#40;NS&#41;&#44; EASI-20&#44;10 &#40;NS&#41;Data not broken down by groups&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"><a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">When multiple measurements were available&#44; the most recent one was used&#44; except in <a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> where only the described data was available&#46;</p>"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Patients who increased the dose interval due to side effects were not included in this table&#46;</p>"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Dose was down-titrated to 200<span class="elsevierStyleHsp" style=""></span>mg of dupilumab every 2 weeks&#46;</p> <p class="elsevierStyleNotepara" id="npar0020">DLQI&#44; Dermatology Life Quality Index&#59; DUPI&#44; dupilumab&#59; EASI&#44; Eczema Area and Severity Index&#59; IGA&#44; Investigator Global Assessment&#59; NS&#44; not significant&#59; P-NRS&#44; Pruritus Numeric Rating scale&#59; QXW&#44; every &#8220;X&#8221; No&#46; of weeks&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Studies in which the dupilumab dose was spaced out due to sustained good response&#46;</p>"
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                      "titulo" => "Patient-centered dupilumab dosing regimen leads to successful dose reduction in persistently controlled atopic dermatitis"
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;S&#46; Spekhorst"
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                            3 => "T&#46; Rispens"
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                        "volumen" => "77"
                        "paginaInicial" => "3398"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dupilumab dose spacing after initial successful treatment or adverse events in adult patients with atopic dermatitis&#58; A retrospective analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C&#46; Patruno"
                            1 => "L&#46; Potestio"
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                        ]
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                    0 => array:2 [
                      "doi" => "10.1111/dth.15933"
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                        "tituloSerie" => "Dermatol Ther&#46;"
                        "fecha" => "2022"
                        "volumen" => "35"
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0040"
              "etiqueta" => "3"
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy and Safety of Multiple Dupilumab Dose Regimens After Initial Successful Treatment in Patients With Atopic Dermatitis&#58; A Randomized Clinical Trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            1 => "E&#46;L&#46; Simpson"
                            2 => "D&#46; Tha&#231;i"
                            3 => "R&#46; Bissonnette"
                            4 => "J&#46;P&#46; Lacour"
                            5 => "S&#46; Beissert"
                          ]
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                      "doi" => "10.1001/jamadermatol.2019.3617"
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                        "tituloSerie" => "JAMA Dermatol&#46;"
                        "fecha" => "2020"
                        "volumen" => "56"
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                      "titulo" => "Longer dupilumab dosing intervals in adult patients with atopic dermatitis&#58; experience from a French multicentre retrospective cohort study"
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                          "etal" => true
                          "autores" => array:6 [
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                            2 => "J&#46; Seneschal"
                            3 => "F&#46; Giordano-Labadie"
                            4 => "N&#46; Raison-Peyron"
                            5 => "A&#46; Du-Thanh"
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                      "doi" => "10.1111/bjd.21628"
                      "Revista" => array:5 [
                        "tituloSerie" => "Br J Dermatol&#46;"
                        "fecha" => "2022"
                        "volumen" => "187"
                        "paginaInicial" => "602"
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                      "titulo" => "Successful Dose Reduction of Dupilumab in Atopic Dermatitis"
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                            0 => "M&#46;R&#46; Ardern-Jones"
                            1 => "E&#46;E&#46; Buchanan"
                            2 => "S&#46; Njungu"
                            3 => "D&#46; O&#8217;Driscoll"
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                      "doi" => "10.1093/bjd/ljad011"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Dermatol&#46;"
                        "fecha" => "2023"
                        "volumen" => "188"
                        "paginaInicial" => "678"
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Foro de Residentes
RF-Longer Dupilumab Dosing Intervals in Atopic Dermatitis: Optimization or Therapeutic Failure?
FR-Espaciamiento de la dosis de dupilumab en dermatitis atópica: ¿optimización o fracaso terapéutico?
M.A. Lasheras-Pérez
Corresponding author
drmalp97@gmail.com

Corresponding author.
, F. Navarro-Blanco, M. Rodríguez-Serna
Servicio de Dermatología y Venereología, Hospital Universitario y Politécnico la Fe, Valencia, Spain
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reduce side effects&#44; and improve economic efficiency&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1&#44;2</span></a> Below we&#8217;ll be discussing the results of 5 studies of patients with well-controlled AD on dupilumab&#44; in whom the dosing interval was extended beyond the above-mentioned 2-week threshold&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The first study to explore this idea was the randomized LIBERTY AD SOLO-CONTINUE clinical trial&#44; which is a continuation of the trials that led to the approval of dupilumab for the management of AD&#46; It studied a total of 422 patients categorized into 4 groups based on the dosing interval&#58; Q1W&#47;Q2W&#44; Q4W&#44; and Q8W&#46; Thirty-six weeks after down-titration&#44; no significant differences were reported in the percentage change observed in the Eczema Area and Severity Index &#40;EASI&#41;&#44; or in the proportion of patients with Investigator Global Assessment &#40;IGA&#41; 0-1 between the Q1W&#47;Q2W and Q4W groups&#46; Conversely&#44; a proportion of patients with EASI-75 was lost &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;045&#41;&#44; and the number of patients with&#44; at least&#44; a 3-point increase in the pruritus numeric rating scale &#40;P-NRS&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; increased&#46; The Q8W group significantly reduced efficacy in the above-mentioned scales&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Afterwards&#44; a Dutch cohort of 90 patients compared the EASI of the Q2W regimen vs the Q4W and Q6W&#47;Q8W regimens&#46; Down-titration was gradual&#44; first to Q3W&#44; and then for those who maintained responses doses were further spaced out&#46; After an&#44; at least&#44; 6-month follow-up&#44; no significant EASI increases were seen in either Q4W or Q6W&#47;Q8W&#46; While the P-NRS remained stable in the Q4W group&#44; it increased in the Q6W&#47;Q8W group &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46; Despite the reduced drug levels&#44; the severity biomarkers PARC&#47;CCL18 and TARC&#47;CCL17 remained low&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">A French series of 88 patients identified 3 predictors of sustained response after dose reduction&#58; spacing due to good sustained response rather than side effects &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;034&#41;&#44; older age &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41;&#44; and lower monthly dose of topical corticosteroids &#40;0&#46;016&#41;&#46; Data from the reviewed studies are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion&#44; various authors propose a consensual and gradual down-titration of dupilumab in well-controlled patients&#46; It has been hypothesized that the sustained response is due to the selection of super responders&#44; in whom a lower drug level saturates the pharmacological target&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1&#44;2&#44;4&#44;5</span></a> Conducting controlled studies aims to avoid iatrogenesis and promote efficiency with the advent of new drugs&#46;</p></span>"
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                  \t\t\t\t">&#37;EASI-0&#46;06&#44; EASI-75 71&#44; 6&#37;&#37;EASI and EASI-75 of the Q1&#47;2W regimen&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">&#37;EASI-0&#46;06&#44; EASI-75 71&#46;6&#37; vs &#37;EASI-0&#46;06&#44; EASI-75 71&#46;6&#37;&#44; &#37;EASI-3&#46;84 &#40;NS&#41;&#44; EASI-75 58&#46;3&#37; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#44; &#37;EASI-6&#46;84 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#44; EASI-75 54&#46;9&#37; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#44; &#37;EASI-21&#46;6 &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; EASI-75 30&#46;4&#37; &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a>&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">Prospective cohort&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"><span class="elsevierStyleHsp" style=""></span>&#62;18 years&#44; 52 weeks Q2W with DUPI 300&#44; EASI &#60;<span class="elsevierStyleHsp" style=""></span>7 for 6 months&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">EASI and P-NRS after 6 months&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">Q2W Q4W Q8W&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 30 30n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>90&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">EASI 6&#46;4&#44; P-NRS 4&#46;0 vs EASI 1&#46;7&#44; P-NRS 2&#46;0&#44; EASI 2&#46;3&#44; P-NRS 2&#46;0 EASI and P-NRS reached by every group before down-titration&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">EASI 5&#46;4 &#40;NS&#41;&#44; P-NRS 4&#46;0 &#40;NS&#41;&#44; EASI 1&#46;5 &#40;NS&#41;&#44; P-NRS 2&#46;0 &#40;NS&#41;&#44; EASI 2&#46;9 &#40;NS&#41;&#44; P-NRS 3&#46;0 &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a>&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 series&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"><span class="elsevierStyleHsp" style=""></span>&#62;18 years&#44; SCORAD50&#44; down-titration&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">Response persistence &#40;unspecified scale&#41; after 6&#46;3 months&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">Q2W Q4W&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">N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>55<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Data not provided in the original article&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">At the 6&#46;3-month follow-up&#44; 35 individuals maintained&#47;increased spacing&#46; Data not provided by the lead author&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"><a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a>&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 series&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"><span class="elsevierStyleHsp" style=""></span>&#62;18 years&#44; 52 weeks Q2W with DUPI 300&#44; EASI&#8804; 7 and DLQI&#8804; 5 for 6 months&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">EASI&#44; P-NRS&#44; DLQI after 32 weeks&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">Q3W Q4W&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">35 9n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>44<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EASI 0&#46;39&#44; P-NRS 1&#46;04&#44; DLQI 3&#46;28 vs EASI 0&#46;18&#44; P-NRS 1&#46;05&#44; DLQI 3&#46;55EASI&#44; P-NRS and DLQI reached by every group before down-titration&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">EASI 0&#46;45 &#40;NS&#41;&#44; P-NRS 0&#46;94 &#40;NS&#41;&#44; DLQI 3&#46;2 &#40;NS&#41;&#44; EASI 0&#46;22 &#40;NS&#41;&#44; P-NRS 1&#46;14 &#40;NS&#41;&#44; DLQI 2&#46;8 &#40;NS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a>&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 series&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"><span class="elsevierStyleHsp" style=""></span>&#62;18 years&#44; 52 weeks Q2W with DUPI 300&#44; IGA 0-1&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">EASI and IGA after 12 months&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">Q3W Q4W Q2W<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>17&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">IGA 1&#46;00&#44; EASI -16&#46;05 IGA and EASI reached by every group before down-titration&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">IGA 1&#46;42 &#40;NS&#41;&#44; EASI-20&#44;10 &#40;NS&#41;Data not broken down by groups&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"><a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">When multiple measurements were available&#44; the most recent one was used&#44; except in <a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> where only the described data was available&#46;</p>"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Patients who increased the dose interval due to side effects were not included in this table&#46;</p>"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Dose was down-titrated to 200<span class="elsevierStyleHsp" style=""></span>mg of dupilumab every 2 weeks&#46;</p> <p class="elsevierStyleNotepara" id="npar0020">DLQI&#44; Dermatology Life Quality Index&#59; DUPI&#44; dupilumab&#59; EASI&#44; Eczema Area and Severity Index&#59; IGA&#44; Investigator Global Assessment&#59; NS&#44; not significant&#59; P-NRS&#44; Pruritus Numeric Rating scale&#59; QXW&#44; every &#8220;X&#8221; No&#46; of weeks&#46;</p>"
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                      "titulo" => "Patient-centered dupilumab dosing regimen leads to successful dose reduction in persistently controlled atopic dermatitis"
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                          "etal" => true
                          "autores" => array:6 [
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                            3 => "T&#46; Rispens"
                            4 => "F&#46; Loeff"
                            5 => "C&#46;M&#46; Boesjes"
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                        "fecha" => "2022"
                        "volumen" => "77"
                        "paginaInicial" => "3398"
                        "paginaFinal" => "3407"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dupilumab dose spacing after initial successful treatment or adverse events in adult patients with atopic dermatitis&#58; A retrospective analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
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                        "fecha" => "2022"
                        "volumen" => "35"
                      ]
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                  ]
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy and Safety of Multiple Dupilumab Dose Regimens After Initial Successful Treatment in Patients With Atopic Dermatitis&#58; A Randomized Clinical Trial"
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                        0 => array:2 [
                          "etal" => true
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                            2 => "D&#46; Tha&#231;i"
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                            4 => "J&#46;P&#46; Lacour"
                            5 => "S&#46; Beissert"
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                      "doi" => "10.1001/jamadermatol.2019.3617"
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                        "tituloSerie" => "JAMA Dermatol&#46;"
                        "fecha" => "2020"
                        "volumen" => "56"
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                      "titulo" => "Longer dupilumab dosing intervals in adult patients with atopic dermatitis&#58; experience from a French multicentre retrospective cohort study"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            2 => "J&#46; Seneschal"
                            3 => "F&#46; Giordano-Labadie"
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                        "fecha" => "2022"
                        "volumen" => "187"
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                      "titulo" => "Successful Dose Reduction of Dupilumab in Atopic Dermatitis"
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                            2 => "S&#46; Njungu"
                            3 => "D&#46; O&#8217;Driscoll"
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                      "doi" => "10.1093/bjd/ljad011"
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                        "tituloSerie" => "Br J Dermatol&#46;"
                        "fecha" => "2023"
                        "volumen" => "188"
                        "paginaInicial" => "678"
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Article information
ISSN: 00017310
Original language: English
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