Multiple sclerosis is a challenging condition that must be continuously monitored because it is treated with numerous drugs.
It is very challenging to treat secondary progressive multiple sclerosis (SPMS) while balancing risks and reducing flare-ups.
- SPMS is a transition of relapsing-remitting multiple sclerosis (RRMS), wherein the flare-ups become more frequent with almost no respite from the symptoms.
- Treatment mainly focuses on the prevention of disability progression. Therefore, most of the drugs used to treat SPMS are pre-approved therapies for RRMS, which are referred to as disease-modifying medications.
Although more potent disease-modifying medications are more successful in minimizing flare-ups in SPMS than safer and less strong treatments, none appears to slow progression more than the other.
What is secondary progressing MS?
Secondary progressive multiple sclerosis is defined by progressing disability with no intermittent recovery. Treatment of these individuals is difficult due to a lack of knowledge of pathophysiology and lack of treatment choices.
Multiple sclerosis is an autoimmune neurological condition in which the myelin sheath around the neurons is damaged, leading to various neurological complications. Multiple sclerosis is a challenging condition that must be continuously monitored because it is treated with numerous drugs, some of which may have major adverse effects.
High-efficacy medications are prescribed in early multiple sclerosis to treat the disease more aggressively and have been shown to prevent flare-ups and modify progression, but it is unclear how effective these therapies may be when relapsing-remitting multiple sclerosis transitions to SPMS.
What are the treatment options for secondary progressive MS?
Disease-modifying therapies (DMTs)
All DMTs given to treat relapsing forms of multiple sclerosis are potential treatment choices for individuals with active secondary progressive multiple sclerosis (SPMS).
- Siponimod: Siponimod, a DMT, is a sphingosine 1-phosphate receptor (S1PR) modulator. S1PR is a protein that forms the structure of myelin around the neurons. Siponimod has shown good efficacy in reducing the risk of progression of disability in people with SPMS. The U.S. Food and Drug Administration (FDA) has approved siponimod for the treatment of adults with active SPMS, which is administered orally. Along with siponimod, other S1PR modulators such as fingolimod, ozanimod, and ponesimod are approved for the treatment of SPMS.
- Fumarates: Dimethyl fumarate, diroximel fumarate, and monomethyl fumarate are oral fumarates that are authorized for the treatment of active SPMS.
- Teriflunomide: Teriflunomide inhibits pyrimidine production and impairs T cell interactions with antigen-presenting cells; it is authorized for the treatment of active SPMS.
- Cladribine: Cladribine, a purine antimetabolite that targets lymphocyte subsets, is licensed to treat active SPMS. Although cladribine is effective in people with relapsing-remitting multiple sclerosis (RRMS), controlled trials have shown only an inconsistent benefit in patients with progressive forms of multiple sclerosis. As a side effect, it may increase the risk of life-threatening infection and tumor growth. As a result, cladribine is often reserved for individuals who do not tolerate or respond adequately to other DMTs for multiple sclerosis.
- Interferons: Interferons are injectable DMTs that are administered intravenously. Studies reported that interferons did not reduce the risk of disability progression in people with SPMS, especially those with an acute inflammatory component. However, it is revealed that interferons have been successful in reducing the risk of at least one relapse.
Monoclonal antibodies DMTs
- Rituximab: Rituximab is a recombinant monoclonal antibody that is considered to work largely by decreasing culprit CD20-positive B cells. Rituximab is commonly used off-label to treat people with active types of multiple sclerosis. A retrospective cohort study of SPMS patients using varied doses of rituximab reported that patients treated with rituximab had lower expanded disability status scale scores and a delayed time to confirm disability progression than control patients who were never treated with rituximab.
- Ocrelizumab: Ocrelizumab is a recombinant human anti-CD20 monoclonal antibody that is regarded as an effective treatment option in people with RRMS and primary-progressive multiple sclerosis (PPMS), which was later approved by the FDA for the treatment of SPMS.
- Natalizumab: Natalizumab is a humanized recombinant monoclonal antibody that targets the alpha-4 subunit of integrin molecules, prevents integrin interaction with vascular receptors, and restricts leukocyte adherence and transmigration (movement from one place to another). Natalizumab has been authorized to treat active SPMS. However, the efficacy of natalizumab for progressive forms of multiple sclerosis is unknown. Studies indicate that natalizumab does not delay disability development in people with SPMS.
- Ofatumumab: Ofatumumab is a humanized monoclonal antibody that selectively deteriorates B cells by targeting CD20 (a protein found on the surface of normal B lymphocytes). Ofatumumab was authorized for relapsing types of multiple sclerosis, including active SPMS.
- Alemtuzumab: Alemtuzumab is a humanized monoclonal antibody that diminishes CD52-expressing T cells, B cells, natural killer cells, and monocytes. Alemtuzumab is authorized to treat relapsing types of MS, such as RRMS and active SPMS. Alemtuzumab is typically reserved for patients with extremely active RRMS who have had an unsatisfactory response to two or more DMTs or if other DMTs cannot be taken due to its adverse effect profile.
- Mitoxantrone: A few small, randomized studies report that mitoxantrone is beneficial for people with deteriorating RRMS or SPMS. However, due to the risk of major consequences (especially cardiotoxicity and leukemia) and the availability of alternatives, the medicine is rarely prescribed.
- Glucocorticoids: Intravenous glucocorticoids such as methylprednisolone have been used alone or in conjunction with other immunomodulatory or immunosuppressive drugs to treat PPMS or SPMS. Although long-term use of glucocorticoids does not appear to produce functional recovery from an attack, regular pulse glucocorticoids may be useful in the long-term management of patients with SPMS, particularly those who continue to have acute attacks in addition to progression between relapses.
- Cyclophosphamide: There is little evidence that pulse with booster cyclophosphamide may assist people younger than 40 years with progressive multiple sclerosis. However, most of the studies revealed that cyclophosphamide therapy has little effect on the progression of progressive multiple sclerosis.
- Methotrexate: Based on limited and contradictory results from a single study, oral or subcutaneous methotrexate, given with or without monthly glucocorticoid pulses, has been used to treat individuals with progressive forms of multiple sclerosis. Only a tendency toward improvement in symptoms and radiographic results were identified in the only high-quality randomized controlled study examining oral methotrexate for progressive multiple sclerosis.
- Azathioprine: Azathioprine has been researched in both RRMS and chronic progressive multiple sclerosis. A systematic review of five randomized, controlled trials of azathioprine versus placebo for multiple sclerosis including patients with RRMS and PPMS discovered that azathioprine significantly reduced the number of relapses and reduced disability progression during the first two to three years of treatment.
- Stem cell transplantation: Stem cell transplantation has shown promising results in treating people with progressive forms of MS.
- Biotin: Biotin is a coenzyme for various carboxylases involved in the fatty acid synthesis, energy generation, axonal remyelination through enhanced myelin formation, and decreased axonal hypoxia through increased energy production. Despite early promise, studies have reported that biotin has shown no consistent benefit in improving disability or walking speed in patients with inactive SPMS or PPMS.
- Simvastatin: Controlled studies on people with SPMS revealed that simvastatin has significantly reduced the rate of brain atrophy and disability. However, it showed no difference in information and progression of new lesions or relapse rate. Further studies are needed to determine if simvastatin slows the course of impairment in SPMS individuals.