<h2>Why Dupixent</h2>
<h3>Conventional therapies may not be enough</h3>
<p>TOO MANY PATIENTS ARE LIVING with UNCONTROLLED SKIN CONDITIONS DRIVEN BY TYPE 2 INFLAMMATION<sup>3,4</sup>…</p>
<p>With long-term consequences beyond what they feel and see on their skin<sup>5-8</sup></p>

<p>Overview</p>

<p>Global impact</p>

<p>Footnotes &amp; Abbreviations &amp; References</p>

<h2>Disease burden</h2>
<h3><span style="color:hsl( 170, 85%, 33% );">Unmet needs</span></h3>

<h3 style="text-align:center;">ARE YOUR PATIENTS WITH UNCONTROLLED AD SHARING THE FULL IMPACT OF THEIR DISEASE?</h3>

Uncontrolled on therapy

<h3 style="text-align:center;">THE CONTINUOUS BURDEN OF UNCONTROLLED AD CAN ACCUMULATE OVER TIME<sup>3</sup></h3>

Lost work productivity

Depression and anxiety

Flares

Lost sleep

<h3 style="text-align:center;">THE UNDERSTANDING OF AD BURDEN HAS EVOLVED BEYOND JUST THE CLINICALLY MEASURABLE IMPACT ON ITCH, SKIN, AND QoL<sup>24</sup></h3>

Impact on Itch, Skin, and QoL

SPECIALTY-CARE

DUPIXENT

ATOPIC-DERMATITIS

DERMATOLOGY

<h3><span style="color:hsl( 170, 85%, 33% );">WHICH UNCONTROLLED PATIENTS HAVE YOU SEEN IN YOUR PRACTICE?</span></h3>

<p>“It’s hard to watch him suffer every day. We’re concerned about the constant itch affecting his sleep.”</p>

<p>“I’m concerned that if I stay on topical steroids, I’ll start to see stretch marks on my skin.”</p>

<p>“I’m ready to try anything to get the flares under control and start getting better sleep.”</p>

<p>“I’m willing to consider any options that can help improve my overall skin health and my feelings of anxiety.”</p>

<p style="text-align:center;" data-font="small">Hypothetical atopic dermatitis cases. Not real patients.</p>

Childhood impact

TCS concerns

Flares & poor sleep

Skin & Mental health

<p>Abbreviations &amp; References</p>

<figure class="table" style="width:100%;">
 <table style="background-color:#0D9B83;border-color:#0D9B83;border-style:solid;">
  <tbody>
   <tr>
    <td style="background-color:#0D9B83;border-color:#0D9B83;padding:15px;">
     <h3><span style="color:hsl(0, 0%, 100%);">TWO KEY DRIVERS OF TYPE 2 INFLAMMATION, &nbsp;IL-4 AND IL-13, SIGNAL THROUGH IL-4Rα</span></h3>
    </td>
   </tr>
  </tbody>
 </table>
</figure>
<p>IL-4 is a key upstream modulator of Th2 response, &nbsp;promoting a positive feedback loop that contributes to increased secretion of IL-4, IL-13, and IL-31<sup>1-7,a</sup></p>
<p>IL-4 and IL-13 play overlapping yet distinct roles in type 2 inflammation<sup>8</sup></p>
<p>Dysregulation of IL-4 and IL-13 signaling in the immune system of patients with AD leads to:</p>
<figure class="table" style="width:100%;">
 <table style="background-color:#D5EAE5;border-color:#fff;border-style:solid;">
  <tbody>
   <tr>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:10px;">
     <h4>SKIN</h4>
    </td>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:10px;">
     <h4>SENSORY NEURONS</h4>
    </td>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:10px;text-align:center;">
     <h4>FLARES</h4>
    </td>
   </tr>
   <tr>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:10px;">
     <ul>
      <li>Epithelial barrier disruption<sup>9</sup></li>
     </ul>
    </td>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:10px;" rowspan="3">
     <ul>
      <li>Itch-scratch cycle<sup>9</sup></li>
     </ul>
    </td>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:10px;" rowspan="3">
     <ul>
      <li>IL-4 overexpression leads to increased TARC as well as IgE, which is associated with AD flares<sup>10-12</sup></li>
     </ul>
    </td>
   </tr>
   <tr>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:10px;">
     <ul>
      <li>Increased risk of skin infections<sup>9</sup></li>
     </ul>
    </td>
   </tr>
   <tr>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:10px;">
     <ul>
      <li>Skin lesions<sup>9</sup></li>
     </ul>
    </td>
   </tr>
  </tbody>
 </table>
</figure>

<figure class="table" style="width:100%;">
 <table style="background-color:#0D9B83;border-color:#0D9B83;border-style:solid;">
  <tbody>
   <tr>
    <td style="background-color:#0D9B83;border-color:#0D9B83;padding:15px;">
     <h3><span style="color:hsl(0, 0%, 100%);">One target, dual action: by TARGETING IL-4Rα, only DUPIXENT blocks IL-4 and IL-13 signaling, and the type 2 inflammatory cascade that causes itch and skin damage<sup>13</sup></span></h3>
    </td>
   </tr>
  </tbody>
 </table>
</figure>
<p>DUPIXENT is the only biologic that inhibits IL-4 signaling, which &nbsp;initiates and perpetuates the type 2 cytokine cascade<sup>3,13,15,16</sup></p>
<p>DUPIXENT directly inhibits IL-4Rα to impact AD and PN in at least 3 distinct ways<sup>3,9,13-17</sup></p>
<figure class="table" style="width:100%;">
 <table style="border-color:#fff;border-style:solid;">
  <tbody>
   <tr>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:10px;">
     <h4>REDUCES TYPE 2 INFLAMMATION</h4>
    </td>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:10px;">
     <h4>HELPS CLEAR SKIN</h4>
    </td>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:10px;text-align:center;" rowspan="3">
     <h4>HELPS RELIEVE ITCH<sup>13</sup></h4>
    </td>
   </tr>
   <tr>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:10px;">
     <ul>
      <li>Disrupts IL-4 feedback loop<sup>8</sup></li>
     </ul>
    </td>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:10px;">
     <ul>
      <li>Clinically proven to improve skin symptoms<sup>13</sup>&nbsp;</li>
     </ul>
    </td>
   </tr>
   <tr>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:10px;">
     <ul>
      <li>May reduce important type 2 inflammatory markers, including TARC and IgE (AD)<sup>18</sup></li>
     </ul>
    </td>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:10px;">
     <ul>
      <li>Significant improvement in skin clearance<sup>13</sup></li>
     </ul>
    </td>
   </tr>
  </tbody>
 </table>
</figure>

<figure class="table" style="width:100%;">
 <table style="background-color:#0D9B83;border-color:#0D9B83;border-style:solid;">
  <tbody>
   <tr>
    <td style="background-color:#0D9B83;border-color:#0D9B83;padding:15px;">
     <h3><span style="color:hsl(0,0%,100%);">IgE and TARC (CCL17) play important roles in AD</span></h3>
    </td>
   </tr>
  </tbody>
 </table>
</figure>
<figure class="table" style="width:100%;">
 <table style="background-color:#d5eae5;border-color:#fff;border-style:solid;">
  <tbody>
   <tr>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:1rem;">
     <h4>IgE</h4>
    </td>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:1rem;">
     <h4>TARC</h4>
    </td>
   </tr>
   <tr>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:1rem;">
     <ul>
      <li>Produced by B cells in the presence of IL-4 and an important <strong>type 2 inflammatory marker</strong><sup>15,27</sup></li>
      <li>An indicator of AD <strong>severity</strong><sup>15,28</sup></li>
      <li>Elevated IgE levels are associated with increased flare risk and a <strong>higher risk of developing atopic comorbidities</strong><sup>15,29</sup></li>
     </ul>
    </td>
    <td style="background-color:#D5EAE5;border-color:#fff;padding:1rem;">
     <ul>
      <li>A chemokine for attracting cells into the skin, promoting <strong>inflammation</strong><sup>30,31</sup></li>
      <li>An indicator of AD <strong>severity</strong><sup>30</sup></li>
      <li>Elevated TARC leads to a <strong>&gt;4x increased risk</strong> of moderate or severe AD in the first 2 years<sup>30</sup></li>
     </ul>
    </td>
   </tr>
  </tbody>
 </table>
</figure>
<h3>DUPIXENT may help lower IgE and TARC</h3>
<ul>
 <li>In a study of 780 patients (placebo groups n=287) with moderate-to-severe* AD treated with DUPIXENT, total IgE reduction range was <strong>-71%</strong> to <strong>-58%</strong> vs <strong>-21%</strong> to <strong>28%</strong> with placebo (P&lt;0.0001)<sup>18</sup></li>
 <li>In the same study, TARC reduction range with DUPIXENT was <strong>-83%</strong> to <strong>-72%</strong> vs <strong>-15%</strong> to <strong>-2%</strong> with placebo (P&lt;0.0001)<sup>18</sup></li>
</ul>
<p data-font="small">*Dupixent is only approved for severe AD in children from 6 months to 11 years old</p>

Role of IgE and TARC

<p>Adult data</p>

<p>HFE</p>

<p>Efficacy (adults)</p>

<p>Infant &amp; young child data</p>

<p>Skin visualizer (all ages)</p>

<p>Study designs</p>

<h2>Safety</h2>
<h3><span style="color:hsl( 170, 85%, 33% );">DUPIXENT HAS DEMONSTRATED LONG-TERM SAFETY AND TOLERABILITY<sup>1</sup></span></h3>

<p>Safety profile</p>

<p>Adverse reactions</p>

<h2>Dosing</h2>
<h3><span style="color:hsl( 170, 85%, 33% );">DOSING IN ATOPIC DERMATITIS<sup>1,a</sup></span></h3>

<h3>Self-inject with confidence (patients 2+ years of age)<sup>*</sup></h3>
<p>Patients can self-inject using the pre-filled auto-injection pen.<sup>1,2</sup>
 <br>
 Provide proper training to patients and/or caregivers on the preparation and administration of DUPIXENT prior to use.</p>
<p>*In children 12 years of age and older, it is recommended that dupilumab is administered by or under supervision of an adult. In children 6 months to less than 12 years of age, dupilumab should be given by a caregiver.</p>
<h3>A fast and simple experience</h3>
<p>The DUPIXENT pre-filled auto-injection pen is designed for patients</p>
<ul>
 <li>No reconstitution needed</li>
 <li>Buttonless activation</li>
 <li>Clear visual feedback</li>
 <li>Injection takes seconds</li>
 <li>14-day out-of-fridge storage at room temperature</li>
</ul>

Self-inject

<h3>ADULTS (18+ YEARS)</h3>
<ul>
 <li>DUPIXENT provides you and your patients with a pre-filled syringe or the choice of an auto-injection pen (patients 2+ years)<sup>1</sup></li>
 <li>Provide proper training to patients and/or caregivers on the preparation and administration of DUPIXENT prior to use.</li>
</ul>

Adults (18+ years)

<h3>ADOLESCENTS (12-17 YEARS)</h3>
<ul>
 <li>DUPIXENT provides you and your patients with a pre-filled syringe or the choice of an auto-injection pen (patients 2+ years)<sup>1</sup></li>
 <li>Provide proper training to patients and/or caregivers on the preparation and administration of DUPIXENT prior to use.</li>
</ul>

Adolescents (12-17 years)

<h3>CHILDREN (6-11 YEARS)</h3>
<ul>
 <li>DUPIXENT provides you and your patients with a pre-filled syringe or the choice of an auto-injection pen (patients 2+ years)<sup>1</sup></li>
 <li>Provide proper training to patients and/or caregivers on the preparation and administration of DUPIXENT prior to use.</li>
</ul>

Children (6-11 years)

<h3>INFANTS (6 MONTHS TO 5 YEARS)</h3>
<ul>
 <li>DUPIXENT provides you and your patients with a pre-filled syringe or the choice of an auto-injection pen (patients 2+ years)<sup>1</sup></li>
 <li>Provide proper training to patients and/or caregivers on the preparation and administration of DUPIXENT prior to use.</li>
</ul>

Infants (6 months to 5 years)

<p>Start/Stay</p>

<p>Tapering off steroids</p>

<p>BIODAY REGISTRY 18+ YEARS</p>

<p>Summary</p>

<p>Heeft u vragen of wilt u meer weten? Wij zorgen dat u zo snel mogelijk geholpen wordt.</p>


Wij staan klaar

DUPIXENT is the first and only dual inhibitor of IL-4 and IL-13 signaling, targeting an important mechanism of inflammation common across a range of skin diseases.

Dupixent - AD

<p>Verlies van het reukvermogen is een belangrijk symptoom van chronische rhinosinusitis met neuspoliepen en treft tot wel 90% van de patiënten.<sup>1,2</sup> Reukverlies, dat leidt tot een aanzienlijke impact op het dagelijks leven en een psychologische ziektelast<sup>3</sup>, is een belangrijke indicator van type 2-inflammatie<sup>4</sup> en kan het eerste teken zijn van een terugkeer van de ziekte.<sup>1,2</sup></p>

<figure class="table" style="width:100%;">
 <table style="background-color:#7A00E6;border-color:#7A00E6;border-style:solid;">
  <tbody>
   <tr>
    <td style="background-color:#7A00E6;border-color:#7A00E6;">
     <h3 style="text-align:center;"><span style="color:hsl(0,0%,100%);">Type 2 Inflammatie en reukverlies</span></h3>
    </td>
   </tr>
  </tbody>
 </table>
</figure>

<ul>
 <li data-list-item-id="ed7e7b3c493cc43fdf71bcc47cd1bf562"><span style="color:hsl(272,100%,45%);"><strong>Reukverlies</strong></span> is een van de meest impactvolle symptomen van CRSwNP<sup>1,2</sup></li>
 <li data-list-item-id="ec907b70d96acc2bd00942277e269b195">Het heeft een <span style="color:hsl(272,100%,45%);"><strong>impact op de kwaliteit van leven</strong></span><sup>3</sup> van patiënten en kan zelfs na een operatieaanhouden<sup>4</sup></li>
 <li data-list-item-id="e3402a7be3c5f583a2d60b85bd4e4e15e"><span style="color:hsl(272,100%,45%);"><strong>Type 2 inflammatie</strong></span> kan een rol spelen bij het ontstaan van anosmie of hyposmie<sup>5</sup></li>
 <li data-list-item-id="ea5746d1f025e50a4872cba10f55320a6"><span style="color:hsl(272,100%,45%);"><strong>Ongeveer 90%</strong></span> van de CRSwNP-patiënten ervaart reukverlies<sup>1</sup></li>
 <li data-list-item-id="e50a8b8b1647df80bb289d202a9cef9de"><span style="color:hsl(272,100%,45%);"><strong>Anosmie of hyposmie</strong></span> kan een teken zijn van een terugkerende ziekte<sup>1,2</sup></li>
 <li data-list-item-id="e276a1154f4b57bdb867760c5d5a33828"><span style="color:hsl(272,100%,45%);"><strong>De mate van type 2 inflammatie</strong></span> correleert met de <span style="color:hsl(272,100%,45%);"><strong>ernst van het reukverlies</strong></span><sup>1,2</sup></li>
</ul>

<figure class="table" style="width:100%;">
 <table style="background-color:#7A00E6;border-color:#7A00E6;border-style:solid;">
  <tbody>
   <tr>
    <td style="background-color:#7A00E6;border-color:#7A00E6;">
     <h3 style="text-align:center;"><span style="color:hsl(0,0%,100%);">Reukverlies wordt in verband gebracht met type 2 inflammatie<sup>5-9</sup></span></h3>
    </td>
   </tr>
  </tbody>
 </table>
</figure>

<figure class="table" style="width:100%;">
 <table style="background-color:#7A00E6;border-color:#7A00E6;border-style:solid;">
  <tbody>
   <tr>
    <td style="background-color:#7A00E6;border-color:#7A00E6;">
     <h3 style="text-align:center;"><span style="color:hsl(0,0%,100%);">Reukverlies vormt een zware last voor CRSwNP-patiënten<sup>1,2</sup></span></h3>
    </td>
   </tr>
  </tbody>
 </table>
</figure>

<p style="text-align:center;">Verminderde kwaliteit van leven (HR-QoL)<sup>1,10</sup></p>

<p style="text-align:center;">Dagelijkse activiteiten worden beïnvloed<sup>3</sup></p>

<p style="text-align:center;">Depressie, angst, fobie, vermoeidheid, irritatie, enz.<sup>3</sup></p>

<p style="text-align:center;">Invloed op persoonlijke relaties<sup>11</sup></p>

<p style="text-align:center;">Economische last, verminderde productiviteit<sup>12</sup></p>

<figure class="table" style="width:100%;">
 <table style="background-color:#7A00E6;border-color:#7A00E6;border-style:solid;">
  <tbody>
   <tr>
    <td style="background-color:#7A00E6;border-color:#7A00E6;">
     <h3 style="text-align:center;"><span style="color:hsl(0,0%,100%);">Reukverbetering als maat voor ziektecontrole</span></h3>
    </td>
   </tr>
  </tbody>
 </table>
</figure>

<p>benadrukken het belang van reukverlies als behandeldoel<sup>13-14</sup></p>

<p>bij de klinische beoordeling van CRS<sup>1</sup></p>

<p>Is complex en vereist een multidisciplinaire aanpak<sup>19-21</sup></p>

<p>Referenties en Afkortingen</p>

Chronische Rhinosinusitis met Nasale Poliepen (CRSwNP): De verbinding tussen Type 2 Inflammatie en Reukverlies

CHRONIC-RHINOSINUSITIS-WITH-NASAL-POLYPS-CRSWNP

RESPIRATORY

<h2>ASCVD is the world's biggest killer.<sup>1</sup>&nbsp;
 <br>
 To take it on, we need to be nothing less than unstoppable.</h2>
<p>Since PRALUENT*'s (alirocumab) approval by the EMA in 2015,<sup>2</sup> to this very day, we have been <strong>working collectively with patients and healthcare professionals against ASCVD</strong>.</p>
<p>Between <strong>unstoppably investigating</strong> LDL-C reduction and CV event prevention, constant <strong>innovation</strong>, and continuous <strong>collaboration</strong> with healthcare professionals to bridge gaps in lipid management, <strong>being unstoppable has taken us far</strong>.<sup>3-8</sup></p>
<p>But it's only just the start.</p>
<p data-font="small">*Primary hypercholesterolaemia and mixed dyslipidaemia : Praluent is indicated in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, and in paediatric patients 8 years of age and older with heterozygous familial hypercholesterolaemia (HeFH) as an adjunct to diet: - - in combination with a statin or statin with other lipid lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin or, alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated. Established atherosclerotic cardiovascular disease - Praluent is indicated in adults with established atherosclerotic cardiovascular disease to reduce cardiovascular risk by lowering LDL-C levels, as an adjunct to correction of other risk factors: - - in combination with the maximum tolerated dose of a statin with or without other lipid-lowering therapies or, alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.</p>

<p>Since PRALUENT's first approval, we've been unstoppably generating evidence to better understand its efficacy and safety profile across various ASCVD populations:<sup>3-7</sup></p>

<h3><span style="color:hsl( 191, 92%, 41% );">2015-2020 - ODYSSEY phase 3 programme</span></h3>
<p>The ODYSSEY phase 3 programme - encompassing 11 distinct phase 3 trials - investigated PRALUENT's impact on LDL-C reduction and CV outcomes across high-risk populations.<sup>3,10-20</sup></p>

<h3><span style="color:hsl(191,92%,41%);">2020 - SYDNEY device study and CHOICE I</span></h3>
<p>The SYDNEY device study and CHOICE I trial investigated PRALUENT 300 mg once-monthly in high-risk populations.<sup>4,5</sup></p>

<h3><span style="color:hsl( 191, 92%, 41% );">2025 - ODYSSEY post hoc pooled analysis</span></h3>
<p>The pooled analysis of phase 3 ODYSSEY studies assessed PRALUENT's effect on LDL-C reduction in ASCVD patients who had not yet experienced a first CV event.<sup>6</sup></p>

<h3><span style="color:hsl( 191, 92%, 41% );">2026 ongoing - OPTIMUS programme</span></h3>
<p>Through the OPTIMUS programme, we're continuing to explore treatment approaches in ASCVD management with real-world and simulation studies utilising advanced methodologies.<sup>7,9*</sup></p>

<p data-font="small">*RWE studies can vary substantially in their methodological approaches, which may contribute to heterogeneity or unexpected findings across analyses. Ensuring that key epidemiological principles - such as appropriate time-zero definition, new-user design considerations, handling of open claims data, and assessment of potential time-related biases - are rigorously applied remains essential to generating reliable insights. High-quality RWE therefore depends on robust and methodologically advanced approaches such as propensity score matching and G-computation used in the studies.</p>

<h3>Over the last decade, we've remained committed to the patient and HCP experience by unstoppably innovating.</h3>
<p>In 2016, the PRALUENT 300 mg once-monthly dose was approved in the EU.<sup>21</sup> Then, with the release and development of devices like SYDNEY and the Next-Gen pen, PRALUENT became and remains the only PCSK9i with a once-monthly single injection in a pre-filled pen.<sup>22*</sup></p>

<p>Through initiatives like the ACS EuroPath programme, we've been <strong>unstoppably identifying gaps in LDL-C management and working with cardiologists</strong> to help bridge them.<sup>8</sup></p>
<p>With surveys conducted in 2018, 2022 and 2024, we've been able to gain insights into <strong>how lipid management has changed over the years</strong> and where there are still <strong>opportunities for improvement.</strong><sup>8</sup> By <strong>collaborating with cardiologists</strong> on dyslipidaemia guideline implementation, we've also shown how enhanced guideline adherence can help improve outcomes for ACS patients.<sup>8</sup></p>

<h2>Key findings from our latest ACS EuroPath programme include</h2>

<p>Lipid management of ACS patients has continuously improved from 2018 to 2024.<sup>8</sup></p>

<p>Suboptimal LDL-C goal attainment persists, emphasising need for sustained efforts to help improve outcomes for ACS patients.<sup>8</sup></p>

<p>Training cardiologists on dyslipidaemia guidelines helped improve outcomes for patients.<sup>8</sup></p>

<h3>For over 10 years, we've never paused in making progress against ASCVD</h3>
<p>We've been unstoppably generating evidence. Unstoppably innovating. Unstoppably collaborating with healthcare professionals to help improve outcomes for patients.<sup>3-8,22</sup></p>
<p>But it's only just the start.
 <br>
 Here's to the next 10 years being unstoppable against ASCVD.
 <br>
 Are you coming with us?</p>

<p>Indication &amp; dosing information</p>

<p>Referenties</p>

Unstoppable commitment to ASCVD care for over 10 years

GENERAL-MEDICINES

CV-T-CORE

PRALUENT

DYSLIPIDEMIA

CARDIOLOGY

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De ADCT geeft een indicatie van hoe gecontroleerd het eczeem is. Beantwoord deze 6 eenvoudige vragen met uw patiënt om de ADCT-score te vinden. Het zal de juiste handelwijze aangeven.

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