Management of breakthrough disease in patients with multiple sclerosis: when an increasing of Interferon beta dose should be effective?

<p>Abstract</p> <p>Background</p> <p>In daily clinical setting, some patients affected by relapsing-remitting Multiple Sclerosis (RRMS) are switched from the low-dose to the high-dose Interferon beta (IFNB) in order to achieve a better control of the disease.</p> <p>Purpose</p> <p>In this observational, post-marketing study we reported the 2-year clinical outcomes of patients switched to the high-dose IFNB; we also evaluated whether different criteria adopted to switch patients had an influence on the clinical outcomes.</p> <p>Methods</p> <p>Patients affected by RRMS and switched from the low-dose to the high-dose IFNB due to the occurrence of relapses, or contrast-enhancing lesions (CELs) as detected by yearly scheduled MRI scans, were followed for two years. Expanded Disability Status Scale (EDSS) scores, as well as clinical relapses, were evaluated during the follow-up period.</p> <p>Results</p> <p>We identified 121 patients switched to the high-dose IFNB. One hundred patients increased the IFNB dose because of the occurrence of one or more relapses, and 21 because of the presence of one or more CELs, even in absence of clinical relapses. At the end of the 2-year follow-up, 72 (59.5%) patients had a relapse, and 51 (42.1%) reached a sustained progression on EDSS score. Overall, 85 (70.3%) patients showed some clinical disease activity (i.e. relapses or disability progression) after the switch.</p> <p>Relapse risk after increasing the IFNB dose was greater in patients who switched because of relapses than those switched only for MRI activity (HR: 5.55, p = 0.001). A high EDSS score (HR: 1.77, p < 0.001) and the combination of clinical and MRI activity at switch raised the risk of sustained disability progression after increasing the IFNB dose (HR: 2.14, p = 0.01).</p> <p>Conclusion</p> <p>In the majority of MS patients, switching from the low-dose to the high-dose IFNB did not reduce the risk of further relapses or increased disability in the 2-year follow period.</p> <p>Although we observed that patients who switched only on the basis on MRI activity (even in absence of clinical attacks) had a lower risk of further relapses, larger studies are warranted before to recommend a switch algorithm based on MRI findings.</p

Dendrimers: breaking the paradigm of current musculoskeletal autoimmune therapies

The advances achieved by cell-based therapies to treat autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS), despite promising, are still insufficient for the current demands. RA and MS therapeutic approaches follow world guidelines to use disease modifying drugs and biological agents that, regardless of some good results in clinical outcomes, are well known for several systemic secondary side effects. Dendrimers are custom-made nanoparticles with proved clinical potential, displaying proper size, chemistries, immunomodulatory, and anti-inflammatory properties. This has directed their potential use as drug delivery systems for cancer therapy, for instance. This review manuscript discloses the hidden potential behind dendrimers as alternative viable solutions to treat RA and MS, by focusing in the most recent reports describing the use of dendrimers for suppressing inflammation and possibly preventing disease progression. The advantages of their use as compared with current applied therapies is also discussed herein.This work was developed under the scope of the Project NORTE‐08‐ 5369‐FSE‐000044 to which the author Daniel B. Rodrigues acknowledges for his PhD grant. The author Tírcia C. Santos acknowledges to the Fundação para a Ciência e Tecnologia (FCT) for her postdoc grant (SFRH/BPD/101952/2014). The FCT distinction attributed to Joaquim M. Oliveira under the Investigador FCT program (IF/01285/ 2015) is also greatly acknowledged.info:eu-repo/semantics/publishedVersio