The world of autoimmune diseases has achieved an accelerated breakthrough in recent years with the advent of powerful disease-modifying drugs. We now have in our arsenal a small but growing number of therapies proven to provide better clinical results than conventional therapies. 

Research into autoimmune conditions is gaining pace as the global incidence of autoimmune diseases continues to rise. Autoimmune diseases are a curious group of diseases because they are the biological equivalent of “self-harm.” What provokes the body to see parts of itself as foreign and hence mount an attack on it? This key question remains a mystery. 

Neuromyelitis optica spectrum disorder (NMOSD) is a chronic inflammatory autoimmune disease that affects the central nervous system (CNS); 2 of its main manifestations are optic neuritis and transverse myelitis. There currently is a range of therapeutic options available to treat NMOSD. 


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As Contentti and Correale wrote in the Journal of Neuroinflammation, “Currently, long-term NMOSD relapse prevention includes off-label use of immunosuppressants, particularly rituximab. In the last 2 years however, three pivotal clinical trials have expanded the spectrum of drugs available for NMOSD patients.” 

Treating Relapses of NMOSD 

The most important aspect of caring for patients with NMOSD is the emergency treatment of relapses.

“NMOSD relapses have significant potential to result in permanent disability, distinct from multiple sclerosis relapses or idiopathic acute transverse myelitis,“ Romeo and Segal wrote in Current Opinion in Rheumatology. “Whereas relapse severity may govern the need for acute treatment in multiple sclerosis, all NMOSD relapses should be treated acutely.” 

In the treatment of NMOSD relapses, time is of the essence. The typical approach to treating NMOSD relapses is using high-dose intravenous (IV) methylprednisolone for the first few days, followed by tapered oral steroids. Approximately 35% of patients achieve complete recovery with IV methylprednisolone treatment. There is substantial evidence to suggest that starting that treatment just 5 days later significantly decreases the chances of recovering completely. 

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If the patient is responding poorly to IV methylprednisolone, plasma exchange or immunoadsorption are recommended as treatment alternatives. Some have suggested that plasma exchange is equally effective as a first-line therapy as IV methylprednisolone, and some advocate using both therapies simultaneously in severe cases.

In any case, the evidence for the urgent start of treatment is again compelling: studies have demonstrated that if plasma exchange is administered immediately, the chances of recovery are 50%, but that figure drops to 1% to 5% if administered after day 20. 

Preventing NMOSD Relapses

Once the worst has passed, attention should turn towards maintenance therapy. Romeo and Segal wrote, “Relapse prevention is essential, as relapses can be disabling and patients may have only partial recovery. Current practice generally recommends at least 5 years of maintenance treatment.” 

This is where things become murkier, as there is no wide consensus on the best treatment regime for this purpose. There is no “first-line” drug for relapse prevention, nor are there guidelines on when to switch medications. This is mainly because the body of medical literature on NMOSD relapse prevention has not yet yielded a conclusive recommendation on treatment approaches.

Contentti and Correale explained, “Off label use of some older immunosuppressive agents such as azathioprine, mycophenolate mofetil, and rituximab have shown reductions in annualized relapse rate (ARR), with disability stabilization in retrospective, prospective, and meta-analysis studies.” 

An often-cited study comparing 2 of those drugs is the one conducted by Nikoo and colleagues in 2017. They compared the efficacy of azathioprine vs rituximab as NMOSD maintenance therapy. They recruited 68 patients with a relapsing-remitting course of NMOSD and randomized them into 2 groups, one (n=35) receiving azathioprine (orally, 50 mg/day) and another (n=33) receiving rituximab (1 g IV, repeated 2 weeks later and then every 6 months). 

The primary outcome was the ARR after 12 months; the secondary outcome was the Expanded Disability Status Scale (EDSS) score. In the azathioprine group, the mean ARR decreased from 1 to 0.51; in the rituximab group, it decreased from 1.30 to 0.21. In addition, the EDSS score after intervention minus the score before intervention was 0.44 in the azathioprine group and 0.98 in the rituximab group. 

Their conclusion? “Azathioprine and rituximab can both effectively decrease ARR and EDSS in NMOSD patients,“ the research team wrote. “However, rituximab was a superior treatment option leading to drug discontinuation.”

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This study is significant because it was the first prospective, randomized clinical trial comparing the efficacy of both drugs as prophylactic medications for relapses and the improvement of disability scores. More clinical trials have since been conducted to evaluate the efficacy of other NMOSD drugs for relapse prevention. 

Contentti and Correale reported, “Advances in the understanding of immune mechanisms involved in NMOSD have led to three recent randomized controlled trials evaluating targeted monoclonal antibodies. Eculizumab was the first monoclonal approved by the FDA to prevent NMOSD relapses in aquaporin-4-antibody-positive patients in June 2019, followed by inebilizumab (June 2020), and satralizumab (August 2020).” 

The future of NMOSD therapies will likely be focused on refining the treatment of relapses and their prevention. With more drugs in the pipeline, the face of NMOSD treatment may yet change in the near future. 

References

Carnero Contentti E, Correale J. Neuromyelitis optica spectrum disorders: from pathophysiology to therapeutic strategiesJ Neuroinflammation. 2021;18(1):208. doi:10.1186/s12974-021-02249-1

Romeo AR, Segal BM. Treatment of neuromyelitis optica spectrum disordersCurr Opin Rheumatol. 2019;31(3):250-255. doi:10.1097/BOR.0000000000000603

Nikoo Z, Badihian S, Shaygannejad V, Asgari N, Ashtari F. Comparison of the efficacy of azathioprine and rituximab in neuromyelitis optica spectrum disorder: a randomized clinical trialJ Neurol. 2017;264(9):2003-2009. doi:10.1007/s00415-017-8590-0