<p style="text-align: center;"><strong>A</strong>cquired</p>

<p style="text-align: center;"><strong>T</strong>hrombotic</p>

<p style="text-align: center;"><strong>T</strong>hrombocytopenic</p>

<p style="text-align: center;"><strong>P</strong>urpura</p>

<p>Acquired or immune-mediated thrombotic thrombocytopenic purpura (aTTP) is a rare blood disorder that develops when the immune system stops ADAMTS13 from working properly. This syndrome is characterized by anemia caused by damage to red blood cells accompanied by a low platelet count, neurologic symptoms, and renal disease.<sup>1</sup></p>
<table border="1" cellpadding="1" cellspacing="1" style="height: 120px; width: 700px;">
 <tbody>
  <tr>
   <td>aTTP share many similarities with other blood diseases, whose treatment algorithms are different from aTTP. Thus, accurate diagnosis is an essential step to accurately prescribe an effective treatment. To do so, ADAMTS13 activity testing should be done.<sup>1</sup></td>
  </tr>
 </tbody>
</table>
<table border="1" cellpadding="1" cellspacing="1" style="width:700px;">
 <tbody>
  <tr>
   <td style="text-align: center; background-color: rgb(68, 11, 18);"><strong><span style="color:#ffffff;">Your role is crucial to the diagnosis and speed of appropriate treatment for aTTP</span></strong></td>
  </tr>
 </tbody>
</table>

<p>ADAMTS13 Activity testing will help confirm or exclude your patient’s TTP disease diagnosis. In addition, the test results may assist clinical decision making in the treatment of aTTP.<sup>2</sup></p>

<p style="text-align: center;">The management of exacerbations and disease relapse is an important aspect of treatment and follow-up of patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP), also known as acquired TTP. Severe ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency during clinical remission is associated with risk of relapse and may guide prophylactic immunemodulatory therapy.</p>

black

<p style="text-align: center;">Patients with TTP in remission should have regular ADAMTS13 activity measurements during follow- up. Although not based on a formal review of published evidence, it is suggested that ADAMTS13 levels should be assessed monthly for the first 3 months, every 3 months through the first year, and every 6–12 months thereafter.1 A decline in ADAMTS13 activity might warrant more frequent measurements, as persistently low levels may increase the risk for relapse.<sup>4,5</sup></p>

<p style="text-align: center;">A blood sample for ADAMTS13 testing (ADAMTS13 activity and inhibitors or anti-ADAMTS13 IgG) should be obtained prior to initiation of therapeutic plasma exchange (TPE) or any blood product in a patient with clinical suspicion of TTP.<sup>4</sup></p>

References

<p>SANOFI, Level 3, One JLT, Jumeirah Lake Towers (JLT), DMCC, PO Box 53899, Dubai, UAE Tel.:&nbsp;<a href="tel:tel:+971 4 550 3600"><span style="color:#0000ee;"><u><strong>+971 4 550 3600</strong></u></span></a>&nbsp;| Fax: +971 4 5521050 For further medical information, please contact: For UAE ✆ 800 MEDICAL Toll-Free Number. For all Gulf countries ✆&nbsp;<a href="tel:tel:+971 45 50 38 63"><span style="color:#0000ee;"><u><strong>+971 45 50 38 63</strong></u></span></a>&nbsp;or email: medical-information.gulf@sanofi.com. To report an adverse event or drug reaction, please contact us on: 24/ 7 Pharmacovigilance reporting number:&nbsp;<a href="tel:tel:+971 561747001"><span style="color:#0000ee;"><u><strong>+971 561747001</strong></u></span></a>&nbsp;e-mail:&nbsp;<a href="mailto:gulf.pharmacovigilance@sanofi.com"><span style="color:#0000ee;"><u><strong>gulf.pharmacovigilance@sanofi.com</strong></u></span></a>&nbsp;SANOFI, SAUDI ARABIA , TAHLIA STREET, NOJOUD CENTER, GATE C, 1ST FLOOR, P.O. BOX 9874, JEDDAH 21423, SAUDI ARABIA For Medical Information: Please contact:<a href="tel:tel:+966126693318"><span style="color:#0000ee;"><u><strong>+966126693318</strong></u></span></a>&nbsp;Email:&nbsp;<a href="mailto:ksa.medicalinformation@sanofi.com"><span style="color:#0000ee;"><u><strong>ksa.medicalinformation@sanofi.com</strong></u></span></a>&nbsp;Website: www.sanofi.com.sa For Pharmacovigilance, Please contact:&nbsp;<a href="tel:tel:+966-54-428-4797"><span style="color:#0000ee;"><u><strong>+966-54-428-4797</strong></u></span></a>,&nbsp;<a href="mailto:ksa_pharmacovigilance@sanofi.com"><span style="color:#0000ee;"><u><strong>ksa_pharmacovigilance@sanofi.com</strong></u></span></a>&nbsp;To report any product technical complaints, kindly contact quality.greatergulf@sanofi.com. To report any side effect(s),Saudi Arabia: The National Pharmacovigilance Centre (NPC): SFDA Call Center: 19999 E-mail:&nbsp;<a href="mailto:npc.drug@sfda.gov.sa"><span style="color:#0000ee;"><u><strong>npc.drug@sfda.gov.sa</strong></u></span></a>&nbsp;Website:<a href="http://https//ade.sfda.gov.sa/"><span style="color:#0000ee;"><u><strong>https://ade.sfda.gov.sa/</strong></u></span></a></p>

ACQUIRED-THROMBOTIC-THROMBOCYTOPENIA-PURPURA-ATTP

RARE-BLOOD-DISORDERS

aTTP is a Medical Emergency With Long Term Consequences

ASTHMA

RESPIRATORY

Airway Hyperresponsiveness
in Asthma

<h2 style="text-align: center;">Proposed Framework for Remission<sup>1-7</sup></h2>

<table border="1" cellpadding="1" cellspacing="1" style="width:500px;">
 <tbody>
  <tr>
   <td style="background-color: rgb(21, 144, 165);">
    <h3 style="text-align: center;"><span style="color:#ffffff;">Remission: A state or period with low to no disease activity that can be spontaneous or as a result of therapy<sup>6</sup></span></h3></td>
  </tr>
 </tbody>
</table>

<h3 style="text-align: center;"><span style="color:#1590a5;">Several Countries Have Recommended Clinical Remission Definitions<sup>1-5</sup></span></h3>

<p data-font="legal"><sup>*</sup>A broad consensus definition is being developed with over 120 experts and is expected in the GEMA 5.4 update.</p>
<p data-font="legal"><sup>†</sup>The US workgroup determined that symptom and lung function criteria must be met on all occasions measured in the previous 12-month period with a minimum of two measurements during the year.</p>

<table border="1" cellpadding="1" cellspacing="1" style="width:500px;">
 <tbody>
  <tr>
   <td style="background-color: rgb(21, 144, 165);">
    <h3 style="text-align: center;"><span style="color:#ffffff;">The definition of on-treatment remission in asthma has not yet been established and further consensus among experts, guidelines, and societies is warranted.<sup>6</sup></span></h3></td>
  </tr>
 </tbody>
</table>
<p><span style="color:#1590a5;"><strong>This tool showcases the evolving evidence around asthma remission as of February 2024 and is intended for educational purposes only.</strong></span></p>
<p data-font="legal">ACQ, Asthma Control Questionnaire; ACT, Asthma Control Test; AirQ, Asthma Impairment and Risk Questionnaire; FEV<sub>1</sub>, forced expiratory volume in 1 second; ICS, inhaled corticosteroids; OCS, oral corticosteroids.</p>

<h2 style="text-align: center;">EVOLUTION OF ON-TREATMENT REMISSION IN ASTHMA</h2>
<h3 style="text-align: center;">How Can Therapeutic Intervention Get Us to On-Treatment Clinical Remission?<sup>6-10</sup></h3>

<h3 style="text-align: center;">Over 70-Years of On-Treatment Clinical Remission in Asthma</h3>

<table border="1" cellpadding="1" cellspacing="1" style="width:500px;">
 <tbody>
  <tr>
   <td style="background-color: rgb(21, 144, 165);">
    <h3 style="text-align: center;"><span style="color:#ffffff;">Remission may be achieved on or off treatment. Different definitions of remission have been proposed and implemented in various studies. Given this evolving framework for remission, further studies may provide a pathway to inform our understanding of disease modification in severe asthma.<sup>6</sup></span></h3></td>
  </tr>
 </tbody>
</table>
<p><span style="color:#1590a5;"><strong>This tool showcases the evolving evidence around asthma remission as of February 2024 and is intended for educational purposes only.</strong></span></p>
<p data-font="legal">ICS, inhaled corticosteroids; LABA, long-acting beta agonist; SABA, short-acting beta agonist; SCS, systemic corticosteroids.</p>

<h2 style="text-align: center;">REDUCING EXACERBATIONS IS A FUNDAMENTAL CRITERION OF ASTHMA REMISSION<sup>1-7</sup></h2>

<p data-font="legal"><sup>*</sup>Adapted from GINA and ERS/ATS.&nbsp;<sup>†</sup>Severe exacerbation was defined as worsening asthma requiring at least 3 days of treatment with systemic corticosteroids, or a hospitalization due to asthma. ATS, American Thoracic Society; BD, bronchodilator; ERS, European Respiratory Society; FEV<sub>1</sub>, forced expiratory volume in 1 second; GINA, Global Initiative for Asthma.</p>

<h2 style="text-align: center;">ZERO OCS USE IS REQUIRED FOR A STATE OF ASTHMA REMISSION<sup>1-7</sup></h2>

<p data-font="legal"><sup>*</sup>Adapted from GINA and ERS/ATS.&nbsp;<sup>†</sup><em>P</em>&lt;0.001.<sup>20</sup><br>
  AE, adverse event; ATS, American Thoracic Society; ERS, European Respiratory Society; GI, gastrointestinal; GINA, Global Initiative for Asthma; OCS, oral corticosteroids.</p>

<h2 style="text-align: center;">ACHIEVING LUNG FUNCTION STABILIZATION OR IMPROVEMENT IS A KEY COMPONENT OF ASTHMA REMISSION<sup>1-7</sup></h2>

<p data-font="legal"><sup>*</sup>Adapted from GINA and ERS/ATS.&nbsp;<sup>†</sup>n=1865; Cox proportional hazard model analysis adjusted for age at index date, smoking status, body mass index, gender, rhinitis, chronic sinusitis, nasal polyps, atopic dermatitis, diabetes, anaphylaxis, ischemic heart disease, heart failure, food allergy, anxiety, depression, and psoriasis.<sup>8 ‡</sup>n=1075; relative risk of death from asthma during 25 years of follow-up.9 ATS, American Thoracic Society; BD, bronchodilator; CI, confidence interval; ERS, European Respiratory Society; FEV<sub>1</sub>, forced expiratory volume in 1 second; FEV<sub>1pp</sub>, FEV<sub>1&nbsp;</sub>percent predicted; GINA, Global Initiative for Asthma; HR, hazard ratio.</p>

<h2 style="text-align: center;">LONG-TERM SYMPTOM CONTROL IS AN IMPORTANT PATIENT-REPORTED COMPONENT OF ASTHMA REMISSION<sup>1-7</sup></h2>

<p data-font="legal"><sup>*</sup>Adapted from GINA and ERS/ATS.<br>
  ACQ, Asthma Control Questionnaire; ACT, Asthma Control Test; ATS, American Thoracic Society; BD, bronchodilator; ERS, European Respiratory Society; FEV<sub>1</sub>, forced expiratory flow in 1 second; GINA, Global Initiative for Asthma.</p>

ON-TREATMENT ASTHMA REMISSION: MOVING BEYOND CONTROL

<p>The ISTH TTP Guidelines are the first evidence-based, international guidelines on the diagnosis, treatment, and management of TTP. The guidelines emphasize the importance of diagnosis through clinical assessment or risk assessment tools, such as the French or PLASMIC score. Clinical assessment can help predict the likelihood of severe ADAMTS13 deficiency in a patient with suspected TTP and guide treatment decisions.<sup>1</sup></p>
<p>Inform your approach to thrombotic thrombocytopenic purpura (TTP) treatment by understanding key clinical considerations and therapeutic options.</p>

The International Society on Thrombosis and Haemostasis (ISTH) TTP Guideline

<p>TTP is a life-threatening thrombotic microangiopathy (TMA) that requires quick diagnosis and urgent treatment.<sup> 1,2</sup></p>

Resources

TTP is a life-threatening thrombotic microangiopathy (TMA) that requires quick diagnosis and urgent treatment.<sup> 1,2</sup>

Discover a solution to control mixed Eosinophilic and Allergic Asthma

<p>Consider this biologic for Patients with mixed Phenotypes.</p>

Open up a world beyond their Asthma symptoms

<p>Give Patients results they can feel with Dupixent.</p>

<h2>It’s Time to Address the Full Spectrum of Type 2 Inflammation in Asthma50%&nbsp;to&nbsp;70%<sup>a</sup>&nbsp;of Adult Patients with Asthma Have Type 2 Inflammation <sup>1</sup></h2>
<h2>GINA Guidelines for difficult - to - treat and severe Asthma</h2>
<h3>Type 2 inflammation is indicated by elevated levels of one or more of the following markers²:</h3>
<ul>
 <li><strong>Blood eosinophils ≥ 150 cells/µL</strong>
  <ul>
   <li><strong>Sputum eosinophils ≥ 2 %</strong><br>
    &nbsp;</li>
  </ul></li>
 <li><strong>Asthma is clinically allergen-driven IgE ≥ 20 IU/mL</strong><br>
  &nbsp;</li>
 <li><strong>FeNO ≥ 20 ppb</strong></li>
</ul>
<p>Biomarkers of Type 2 inflammation may be suppressed by systemic corticosteroid use. This should be taken into consideration when determining Type 2 status in patients taking oral corticosteroids³</p>
<p><sup>ᵃ</sup>N=205.<br><sup>ᵇ</sup>N=37.</p>
<p><strong>Abbreviations</strong></p>
<p><strong>GINA</strong>, Global Initiative for Asthma;&nbsp;<strong>ICS</strong>, inhaled corticosteroid;&nbsp;<strong>LABA</strong>, long-acting beta agonist.</p>

<h2>Type 2 Inflammation</h2>
<h3>IL-4 and IL-13: Central Cytokines that mediate Type 2 Inflammation, including Allergic and Eosinophilic<sup>1,2,3</sup></h3>
<h3>Type 2 inflammation plays an important role in uncontrolled asthma, contributing to increased exacerbations and decreased lung function²</h3>

<h2>Type 2 Inflammation CoMorbidities</h2>
<h3>Type 2 Inflammatory Diseases Share Common Inflammatory Cells and Mediators¹⁻³</h3>

<p data-font="legal"><strong>Abbreviations</strong></p>
<p data-font="legal"><strong>ABPA</strong>, allergic bronchopulmonary aspergillosis;&nbsp;<strong>COPD</strong>, Chronic Obstructive Pulmonary Disease;&nbsp;<strong>CRSwNP</strong>, chronic rhinosinusitis with nasal polyps;&nbsp;<strong>InterILC2</strong>, group 2 innate lymphoid cell;&nbsp;<strong>LC</strong>, Langerhans cell;&nbsp;<strong>NSAID-ERD</strong>, nonsteroidal anti-inflammatory drug exacerbated respiratory disease;&nbsp;<strong>Th</strong>, T helper cell</p>

<h2>Type 2 Asthma includes a range of phenotypes</h2>
<h3>Type 2 Asthma GINA phenotypes¹</h3>

<h2>Real World Evidence on Pheno Types</h2>
<h3>Saudi Arabia Real World Evidence Data for Mixed Phenotype Refractory Asthma¹</h3>
<h4>From Local Saudi Arabia Data, Almost 78% of Severe Ashtma patients with elevated Serum IgE and eosinophilic count<sup>1</sup></h4>
<p>The 78% mixed phynotyping patients have been subcategorized as following<sup>1</sup></p>

<h3>Methods:</h3>
<p>A retrospective cross-sectional real-life study was conducted on patients attending adult refractory asthma outpatient clinic between 2015 and 2018.<sup>1</sup></p>
<p>Serum total IgE level and blood EOS count on matched dates with spirometry and Asthma Control Test (ACT) scores were collected.<sup>1</sup></p>
<p>All data were obtained while patients were not on biological agents.<sup>1</sup></p>

<p data-font="legal"><strong>Fig. 1.</strong>&nbsp;Serum IgE levels and eosinophils count subgroups of patients with refractory severe asthma.</p>

Reference

<h2>Severe Asthma treatment goals</h2>
<h3>Patients with uncontrolled persistent Asthma have a high disease burden<sup>1-9</sup></h3>

<h2>FEV<sub>1</sub>&nbsp;Correlation with AAER</h2>
<h3>Low Fev<sub>1</sub>&nbsp;is a significant predictor of future severe exacerbations</h3>
<p>Patients aged ≥18 years with moderate-to-severe asthma over a 36-month follow-up period (n=1865)</p>

<p data-font="legal">**p&lt;0.01; ****p&lt;0.0001. aCox proportional hazard model analysis adjusted for age at index date, smoking status, BMI, gender, rhinitis, chronic sinusitis, nasal polyps, atopic dermatitis, diabetes, anaphylaxis, ischemic heart disease, heart failure, food allergy, anxiety, depression, and psoriasis. BMI, body mass index; CI, confidence interval; HR, hazard ratioKhan A, et al. Ann Allergy Asthma Immunol. 2018;121:S22–S62</p>

About Type 2 Inflammation – Asthma

Dupixent® (dupilumab) Mechanism of Action

<p>Dupixent binds to IL-4Rα, blocking IL-4 and IL-13 intracellular signaling, Two Type 2 Cytokines that contribute to Inflammation in Asthma.</p>

How does Dupixent support lung function improvement in Pediatric Asthma?

<p>KOL Expert on Lung Function for Pediatric asthma.</p>

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