This activity is for healthcare professionals outside of the UK.

This activity is provided by an independent medical education grant from Sanofi.

The activity is jointly provided by USF Health and touchIME.
touchIME is an EBAC® accredited provider.

Faculty & Disclosures

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    Faculty & Disclosures
    Prof. Xavier Montalban

    Centre d'Esclerosi Múltiple de Catalunya (Cemcat) and Vall d'Hebron University Hospital, Barcelona, Spain

    Prof. Montalban is the director of the Centre d’Esclerosi Múltiple de Catalunya (Cemcat), the chair of Neurology at Universitat de Vic – Universitat Central de Catalunya (UVic-UCC), and the coordinator of Neuroimmunology at the Vall d’Hebron University Hospital Research Institute, Barcelona, Spain. read more

    He also serves as chief of the Neuroimmunology Research Group at the Vall d’Hebron Research Institute (VHIR). His research focuses on magnetic resonance imaging (MRI) and biological prognostic markers to better understand the heterogeneity in disease progression and treatment response in multiple sclerosis (MS). His work also explores the immunological mechanisms of MS and other advances in its clinical management.

    Prof. Montalban directed the development of the first Spanish MS clinical practice Guidelines and, alongside Prof. Ralf Gold, co-led the development of the European guidelines for the treatment of MS.

    Prof. Montalban has authored over 800 original and review publications in national and international peer-reviewed journals, with over 52,000 citations. He has also contributed to several book chapters and has achieved a Scopus H-index of 101.

    Prof. Xavier Montalban discloses: Advisory board/panel fees and consultancy fees from AbbVie, Actelion, Alexion, AstraZeneca, Autolus Therapeutics, BIAL, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic Therapeutics, Indivi, Janssen Pharmaceuticals, Juvisé Pharmaceuticals, Lilly, MedDay Pharmaceuticals, Merck, Mylan/Viatris, NervGen, Neuraxpharm, Novartis, Rewind Therapeutics, Samsung-Biosys, Sandoz, Sanofi-Genzyme, Teva Pharmaceuticals, TG Therapeutics and Zenas BioPharma.
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    Poll

    How confident are you in your understanding of progressive MS pathophysiology?

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    Poll

    What would most help prepare you for the potential use of BTKi in progressive MS?

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    Efficacy data
       
    Safety profile
       
    Monitoring strategies
       
    When to treat
       
     
    Focus Questions
    What are the current guideline-recommended therapies for progressive MS, and what does real-world evidence tell us about their efficacy and safety in clinical practice?
    How does the unified disease framework and its biological drivers inform progression and treatment strategies, particularly in non-active progressive MS?
    What is the rationale for targeting BTK in progressive MS?
    What do the latest clinical trial data tell us about the efficacy and safety of BTK inhibitors in progressive MS?
    What safety considerations should clinicians keep in mind when evaluating BTK inhibitors for use in practice?
    How might BTK inhibitors fit into the current treatment paradigm, and what changes do you foresee in progressive MS management over the next 3–5 years?
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    Multiple Sclerosis, Neuroimmunology CE/CME accredited

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    The potential of BTKi therapies in delaying MS progression

    Take CE/CME Test

    Prof. Montalban is director of the Centre d’Esclerosi Múltiple de Catalunya (Cemcat), chair of Neurology at Universitat de Vic – Universitat Central de Catalunya (UVic-UCC), and coordinator of Neuroimmunology at the Vall d’Hebron University Hospital Research Institute, Barcelona, Spain. read more

    He also serves as chief of the Neuroimmunology Research Group at the Vall d’Hebron Research Institute (VHIR). His research focuses on magnetic resonance imaging (MRI) and biological prognostic markers to better understand the heterogeneity in disease progression and treatment response in multiple sclerosis (MS). His work also explores the immunological mechanisms of the MS and other advances in its clinical management.

    Prof. Montalban directed the development of the first Spanish Multiple Sclerosis Clinical Practice Guidelines for MS and, alongside Prof. Ralf Gold, co-led the development of the European Guidelines for the Treatment of MS.

    Prof. Montalban has authored over 800 original and review publications in national and international peer-reviewed journals, with over 52,000 citations. He has also contributed to several book chapters and holds a Scopus H-index of 101.

    Prof. Xavier Montalban discloses: Advisory board/panel fees and consultancy fees from AbbVie, Actelion, Alexion, AstraZeneca, Autolus Therapeutics, BIAL, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic Therapeutics, Indivi, Janssen Pharmaceuticals, Juvisé Pharmaceuticals, Lilly, MedDay Pharmaceuticals, Merck, Mylan/Viatris, NervGen, Neuraxpharm, Novartis, Rewind Therapeutics, Samsung-Biosys, Sandoz, Sanofi-Genzyme, Teva Pharmaceuticals, TG Therapeutics and Zenas BioPharma.

    Faculty Podcast Featured
    Learning Objectives

    After watching this activity, participants should be better able to:

    • Recall the pathophysiology of progressive MS, including the role of BTK, and assess the potential of investigational BTK inhibitors in targeting disease progression
    • Evaluate approved therapies for progressive MS and define the remaining treatment needs, with an emphasis on emerging approaches such as BTK inhibitors
    Overview

    Join Prof. Montalban as he shares expert insights into the pathophysiology of progressive MS and the rationale for targeting BTK inhibitors. He reviews emerging clinical data supporting the use of BTK inhibitors and discusses how they may fit into the evolving treatment landscape. In this context, Prof. Montalban also considers current guideline-recommended therapies for progressive MS and highlights key areas of remaining unmet treatment need. read more

    Target Audience

    Neurologists, MS specialists and advanced practice clinicians/advanced clinical practitioners (APCs/ACPs) involved in the management of MS.

    USF Accreditation

    Disclosures

    USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

    Faculty

    Prof. Xavier Montalban discloses: Advisory board/panel fees and consultancy fees from AbbVie, Actelion, Alexion, AstraZeneca, Autolus Therapeutics, BIAL, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic Therapeutics, Indivi, Janssen Pharmaceuticals, Juvisé Pharmaceuticals, Lilly, MedDay Pharmaceuticals, Merck, Mylan/Viatris, NervGen, Neuraxpharm, Novartis, Rewind Therapeutics, Samsung-Biosys, Sandoz, Sanofi-Genzyme, Teva Pharmaceuticals, TG Therapeutics and Zenas BioPharma.

    Content reviewer

    John Ciotti, MD, discloses: Advisory board or panel fees from EMD Serono and TG Therapeutics (relationships terminated).

    Touch Medical Contributor

    Christina Mackins-Crabtree has no financial interests/relationships or affiliations in relation to this activity.

    USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

    Requirements for Successful Completion

    In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

    If you have questions regarding credit please contact cpdsupport@usf.edu 

    Accreditations

    Physicians

    This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

    USF Health designates this enduring material for a maximum of 0.5 AMA PRA Category 1 CreditsTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    Advanced Practice Providers

    Physician Assistants may claim a maximum of 0.5 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

    The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

    Date of original release: 30 April 2025. Date credits expire: 30 April 2026.

    If you have any questions regarding credit, please contact cpdsupport@usf.edu

    EBAC® Accreditation

    touchIME is an EBAC® accredited provider since 2023.

    This program is accredited by the European Board for Accreditation of Continuing Education for Health Professionals (EBAC®) for 27 minutes of effective education time.

    EBAC® holds an agreement on mutual recognition of substantive equivalency with the US Accreditation Council for CME (ACCME) and the Royal College of Physicians and Surgeons of Canada, respectively.

    Through an agreement between the European Board for Accreditation of Continuing Education for Health Professionals (EBAC®) and the American Medical Association, physicians may convert EBAC® External CME credits to AMA PRA Category 1 Credits™. Information on the process to convert EBAC® credit to AMA credit can be found on the AMA website. Other healthcare professionals may obtain from the AMA a certificate of having participated in an activity eligible for conversion of credit to AMA PRA Category 1 Credit™.

    EBAC® is a member of the International Academy for CPD Accreditation (IACPDA) and a partner member of the International Association of Medical Regulatory Authorities (IAMRA).

    Faculty Disclosure Statement / Conflict of Interest Policy

    In compliance with EBAC® guidelines, all speakers/chairpersons participating in this programme have disclosed or indicated potential conflicts of interest which might cause a bias in the presentations. The Organizing Committee/Course Director is responsible for ensuring that all potential conflicts of interest relevant to the event have been mitigated and declared to the audience prior to the CME activities.

    Requirements for Successful Completion

    Certificates of Completion may be awarded upon successful completion of the post-test and evaluation form. If you have completed one hour or more of effective education through EBAC® accredited CE activities, please contact us at accreditation@touchime.org to receive your EBAC® CE credit certificate. EBAC® grants 1 CE credit for every hour of education completed.

    Date of original release: 30 April 2025. Date credits expire: 30 April 2027.

    Time to complete: 27 minutes

    If you have any questions regarding the EBAC® credits, please contact accreditation@touchime.org 

    This activity is CE/CME accredited

    To obtain the CE/CME credit(s) from this activity, please complete this post-activity test.

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    Topics covered in this activity

    Multiple Sclerosis / Neuroimmunology
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    This activity is funded by:

    An independent medical education grant from Sanofi.

    The activity is jointly provided by USF Health and touchIME.
    touchIME is an EBAC® accredited provider.

    The information provided by this CME activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

    USF

    USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

    USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CME to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

    Date of original release: 30 April 2025. Date credits expire: 30 April 2026.

    EBAC®

    touchIME is an EBAC® accredited provider since 2023.

    In compliance with EBAC® guidelines, all speakers/ chairpersons participating in this programme have disclosed or indicated potential conflicts of interest which might cause a bias in the presentations. The Organizing Committee/Course Director is responsible for ensuring that all potential conflicts of interest relevant to the event are declared to the audience prior to the CME activities.

    Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

    This content is intended for healthcare professionals outside of the UK.

    Date of original release: 30 April 2025. Date credits expire: 30 April 2027.

    Claim Credit
    touchEXPERT FOCUS
    The potential of BTKi therapies in delaying MS progression
    0.5 CE/CME credit
    Question 1/5
    Which of the following best explains the role of BTK in the pathophysiology of progressive MS?

    BTK, Bruton’s tyrosine kinase; CNS, central nervous system; MS, multiple sclerosis.

    BTK plays a central role in the pathogenesis of progressive MS by regulating B-cell receptor signalling and activating CNS-resident myeloid cells, particularly microglia. These processes contribute to compartmentalized inflammation within the CNS, which is increasingly recognized as a key driver of progression in non-relapsing MS. BTK inhibitors, unlike many other DMTs, can cross the blood–brain barrier and act on these cell populations.

    Abbreviations
    BTK, Bruton’s tyrosine kinase; CNS, central nervous system; DMT, disease-modifying therapy; MS, multiple sclerosis. 

    Reference
    Krämer J, et al. Nat Rev Neurol. 2023;19:289–304.

    Question 2/5
    You are evaluating a 42-year-old with relapsing MS who has shown gradual disability progression over the past 12 months, despite no relapses or new MRI lesions. Based on the unified disease framework, how should this presentation influence your interpretation of their disease course?

    MRI, magnetic resonance imaging; MS, multiple sclerosis.

    The unified disease framework emphasizes that MS is a single, continuous disease in which mechanisms of progression, such as axonal loss, mitochondrial injury and microglial activation, can be active from the earliest stages, even in the absence of relapses or MRI activity.1,2 This case illustrates what may be referred to as progression independent of relapse activity (PIRA), which is increasingly recognized as a major contributor to disability accumulation in MS.1

    Abbreviations

    MRI, magnetic resonance imaging; MS, multiple sclerosis. 

    References

    1. Krieger S, et al. Curr Opin Neurol. 2024;37:189–201.
    2. Kuhlmann T, et al. Lancet Neurol. 2023;22:78–88.

    Question 3/5
    What was a key finding from the EXPAND trial of siponimod in SPMS?

    CDP, confirmed disability progression; SPMS, secondary progressive multiple sclerosis.

    Prior to siponimod, most DMTs for MS were indicated for RRMS and SPMS with relapses. None of these therapies showed consistent efficacy in slowing disability progression.1 The EXPAND trial evaluated siponimod in patients with SPMS and demonstrated a 21% relative risk reduction in 3-month CDP compared with placebo.1 This was the primary endpoint and led to the approval of siponimod for active SPMS in Europe and the USA.1–3 The trial also showed favourable effects on some MRI measures, but no significant improvement in cognitive or fatigue endpoints.2,3

    Abbreviations

    CDP, confirmed disability progression; MRI, magnetic resonance imaging; RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis.

    References

    1. Kappos L, et al. Lancet. 2018;391:1263–73.
    2. EMA. Siponimod. SmPC. Available at: www.ema.europa.eu/en/documents/product-information/mayzent-epar-product-information_en.pdf (accessed 17 April 2025).
    3. FDA. Siponimod. PI. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2024/209884s019lbl.pdf (accessed 17 April 2025).
    Question 4/5
    You are managing two patients:

    Patient A: A 52-year-old woman with non-relapsing SPMS, slowly worsening gait and cognition over 2 years

    Patient B: A 58-year-old man with PPMS, stable on ocrelizumab for 3 years, but reporting gradual worsening

    Based on current understanding and trial data, which patient profile may be more immediately aligned with the proposed mechanism of action and evidence for BTKi therapy?

    BTKi, Bruton’s tyrosine kinase inhibitor; MS, multiple sclerosis; PPMS, primary progressive MS; SPMS, secondary progressive MS.

    The HERCULES trial assessed the efficacy of tolebrutinib in non-relapsing SPMS and reported a 31% reduction in 6-month confirmed disability progression, despite no effect on relapse rate.1

    There are limited trial data to support BTKi efficacy in PPMS at this time.2 Previous exposure to anti-CD20 therapy is not a contraindication to BTKi.1

    Abbreviations

    BTKi, Bruton’s tyrosine kinase inhibitor; MS, multiple sclerosis; PPMS, primary progressive MS; SPMS, secondary progressive MS. 

    References

    1. Fox RJ, et al. N Engl J Med. 2025:doi:10.1056/NEJMoa2415988.
    2. Robertson NP. J Neurol. 2025;272:106.
    Question 5/5
    You’re considering future BTKi therapy, in a trial setting or when approved, for Patient A, the 52-year-old woman with non-relapsing SPMS, slowly worsening gait and cognition over 2 years. She asks if there are any safety concerns.

    Which of the following safety considerations should you discuss with her, based on current BTKi trial data?

    BTKi, Bruton’s tyrosine kinase inhibitor; SPMS, secondary progressive multiple sclerosis.

    In the phase II and III clinical trials of BTKis in MS (e.g., tolebrutinib, evobrutinib), the most consistent safety signal has been elevations in liver enzymes, indicating potential hepatotoxicity.1,2 Although these events were generally reversible, they necessitate regular liver function monitoring, especially during treatment initiation.1,2

    Abbreviations
    BTKi, Bruton’s tyrosine kinase inhibitor; MS, multiple sclerosis.

    References

    1. Fox RJ, et al. N Engl J Med. 2025:doi:10.1056/NEJMoa2415988.
    2. Montalban X, et al. Lancet Neurol. 2024;23:1119–32.
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    This activity is funded by:

    An independent medical education grant from Sanofi.

    The activity is jointly provided by USF Health and touchIME.
    touchIME is an EBAC® accredited provider.

    The information provided by this CME activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

    USF

    USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

    USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CME to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

    Date of original release: 30 April 2025. Date credits expire: 30 April 2026.

    EBAC®

    touchIME is an EBAC® accredited provider since 2023.

    In compliance with EBAC® guidelines, all speakers/ chairpersons participating in this programme have disclosed or indicated potential conflicts of interest which might cause a bias in the presentations. The Organizing Committee/Course Director is responsible for ensuring that all potential conflicts of interest relevant to the event are declared to the audience prior to the CME activities.

    Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

    This content is intended for healthcare professionals outside of the UK.

    Date of original release: 30 April 2025. Date credits expire: 30 April 2027.

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