Prognosis & Management
Initially, the presence of anti-MOG was thought to be associated with fewer relapses and better outcomes than those with AQP-4 positive NMOSD,5,8 but studies with longer follow-up times indicate higher relapse rates than previously reported.4,8
A cohort study from 2016 found that 80% of those in the cohort had a multiphasic disease and an annualized relapse rate (AAR) of 0.9.4,13 They found that one third of patients with optic neuritis and around half of patients with spinal cord inflammation made a full recovery.4,13 In contrast, two other studies showed that the retinal neuro-axonal damage found after an acute attack of optic neuritis was as severe among anti-MOG positive individuals as individuals with AQP-4 positive NMOSD.4
Those with MOG antibody disease should consider ongoing treatment with medications that suppress the immune system. There are no FDA-approved medications for maintenance in MOG antibody disease, so anything prescribed is done off-label. The primary therapies used in the US are mycophenolate mofetil (CellCept), rituximab (Rituxan), azathioprine (Imuran), and repeated IVIG infusions or subcutaneous immunoglobulin. Some studies from the United Kingdom have supported the use of IVIG to prevent relapses.
Some patients presenting with optic neuritis or transverse myelitis who also test positive for the MOG antibody may start treatment after the initial event if the attack was severe and the individual does not want to risk a relapse.
All of these medications carry a risk of infections, particularly upper respiratory infections and urinary tract infections (UTIs). Good hygiene and hand washing are important if on immunosuppressants, as is having a good urologist if at risk for UTIs. There is also the risk with any of these medications of the development of a rare brain infection called progressive multifocal leukoencephalopathy, or PML. PML is an infection caused by the reactivation of a virus, called the JC virus, which lives in the kidney. In someone who is immunosuppressed, this virus can escape the kidney, cross the blood-brain barrier, and enter the brain, causing profound inflammation. Although it can be treated, it is very devastating and sometimes fatal. It is important to know that exposure to these medications in MOG antibody disease has not led to a known case of PML. The known rate of incidence of PML if on Rituxan is estimated at 1 in 25,000 and the rate in CellCept is estimated at 1 in 6,000 based on data from use of these medications for immunosuppression for other purposes. The manufacturer of Imuran cautions about a risk of PML with Imuran as well, but the incidence of PML on Imuran is not documented. Clinical diligence and early intervention are important if PML is suspected.
Chronic immunosuppression requires regular skin exams with a dermatologist since our immune system is our best defense against cancer cells developing, and any of these treatments can interfere with its normal functioning.
Mycophenolate mofetil and azathioprine are both twice daily pills which broadly suppress the immune system. Both medications were originally FDA approved for organ transplant rejection prophylaxis, although azathioprine now is indicated in rheumatoid arthritis, and both have been widely used in several autoimmune disorders. These medications require frequent blood draws upfront, then generally twice yearly to monitor for liver toxicity and to ensure optimal immunosuppression (absolute lymphocyte count around 1 and total white blood cell count between 3 and 4).
Azathioprine is the medication that has been around the longest. However, while the AAR seems to be low on azathioprine, one complication with this medication is that some are not able to stay in remission on azathioprine alone and have to also be on steroids (complications of steroids will be discussed below). Additionally, a long-term study of azathioprine found that the risk of lymphatic-proliferative cancers was reported to be 3%. A common side effect includes gastrointestinal upset, and this may manifest as bloating, constipation, nausea, diarrhea, and may vary throughout the course of one’s time on the medication. Azathioprine is contraindicated in pregnancy, so pregnancy planning is very important. It is FDA Category D (which means don’t take this drug during pregnancy unless it’s lifesaving) and is associated with an increased risk of miscarriages, 7% rate of congenital problems, and high rate of bone marrow suppression that recovers after birth. It is the cheapest of the medications. One study among those with MOG antibody disease found that the mean ARR for azathioprine was 0.99, with 41% of the attacks occurring during the first 6 months, and most of these early attacks were in those who were not also being treated with corticosteroids.3,13
Mycophenolate mofetil has a similar effect on the gastrointestinal system, though many report that the symptoms are milder with mycophenolate as compared with azathioprine. Additionally, some complain of headaches with mycophenolate, particularly in the beginning; these tend to wane with ongoing use. Lymphoma may be a risk of this medication; however, there have been no cases reported in MOG antibody disease patients while on this medication, so the risk is likely low. Mycophenolate is also contraindicated in pregnancy, so, again, planning is imperative. It is also an FDA Category D (don’t take this drug during pregnancy unless it’s lifesaving) and carries a 45% chance of miscarriage. Of those that do not miscarry, 22% have congenital defects mostly in the face (mouth, ears).
Rituximab is an intravascular infusion which works differently from the other two agents listed above. Rather than being a broad immunosuppressant, rituximab completely depletes one particular type of white blood cell called B-cells, which has downstream effects on the rest of the immune system. Though protocols are slightly different, in general, it is given two times twice a year (4 infusions total) and is given in an outpatient infusion center. This is because of a 30% risk of an infusion reaction without pre-medication with some cocktail of methylprednisolone, diphenhydramine and perhaps acetaminophen. The medication is quite well-tolerated. There are generally no side effects to the medication. There is no lymphoma risk with this medication. There is a monthly blood test to monitor the B-cell CD20 expression. Rituximab is safer in pregnancy than the other two previously described, (Category C; may be toxic in animals or no human data) — there are no official FDA reports of birth defects in cases of pregnancy with rituximab, but babies are born with no CD20 cells. It does not appear to increase risk of infection in babies as the cells re-populate within 6-18 months. In monkey studies performed by the manufacturer, there was no toxicity on the fetus, and monkey babies were born with no CD20 cells, again with no infection risks. In the largest case series published in February 2011, out of 153 women who became pregnant on rituximab, there were 4 post-natal infections and two congenital abnormalities (1 club foot, 1 heart defect), but these women were also on other immunosuppressant medications during the pregnancy, including azathioprine and mycophenolate. They concluded that rituximab does not increase the risk of congenital malformations above the natural rate of 1-2%. Planned pregnancy is still recommended. A study looking at rituximab among those with MOG antibody disease found that three out of nine patients experienced a decline in the ARR, and most relapses occurred either soon after an infusion or at the end-of-dose period.13
Low-dose prednisone is used as well, more often outside of the United States. As noted above, some clinicians also use it in combination with azathioprine for those who continue to relapse on azathioprine alone. Its use is oftentimes not favored in the US for maintenance therapy due to the potential complications associated with long-term steroid use, including diabetes, osteoporosis, weight gain, mood instability, hypertension, skin changes, etc.
IVIG has also been used as a maintenance treatment in MOG antibody disease. One retrospective study looked at treatment, AARs, and disability among 59 patients with MOG antibody disease.14 This study included 7 patients who were using IVIG as a maintenance therapy. Out of these 7 patients, 3 had relapses while on treatment with IVIG, with 3 out of 7 (43%) having treatment failure. Half of the relapses that occurred happened when weaning IVIG doses or increasing dosing intervals.14 Another prospective study looking at AARs and disability in 102 children with MOG antibody disease found that maintenance treatment with IVIG reduced the median AAR from 2.16 to 0.51.15 They also found that 4 (33.3%) out of the 12 patients treated with maintenance IVIG relapsed.15 Some physicians may also prescribe subcutaneous immunoglobulin.
Studies have shown that conventional treatments for MS are not effective and may cause adverse reactions in AQP4-positive NMOSD.14 Since there is not enough information about their use in MOG antibody disease, and because they may not reduce relapse rates, or they may lead to adverse effects, treatments for MS are not recommended in MOG antibody disease.15
(3) Dos Passos GR, Oliveira LM, da Costa BK, et al. MOG-IgG-Associated Optic Neuritis, Encephalitis, and Myelitis: Lessons Learned From Neuromyelitis Optica Spectrum Disorder. Front Neurol. 2018 Apr 4;9:217. doi: 10.3389/fneur.2018.00217. eCollection 2018.
(4) Weber MS, Derfuss T, Metz I, Brück W. Defining distinct features of anti-MOG antibody associated central nervous system demyelination. Ther Adv Neurol Disord. 2018 Mar 29;11:1756286418762083. doi: 10.1177/1756286418762083. eCollection 2018.
(5) Lechner C, Baumann M, Hennes EM, et al. Antibodies to MOG and AQP4 in children with neuromyelitis optica and limited forms of the disease. J Neurol Neurosurg Psychiatry. 2016 Aug;87(8):897-905. doi: 10.1136/jnnp-2015-311743. Epub 2015 Dec 8.
(8) Cobo-Calvo A, Ruiz A, Maillart E, et al. Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: The MOGADOR study. Neurology. 2018 May 22;90(21):e1858-e1869. doi: 10.1212/WNL.0000000000005560. Epub 2018 Apr 25.
(13) Jarius S, Ruprecht K, Kleiter I, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflammation. 2016; 13: 280.
(14) Ramanathan S, Mohammad S, Tantsis E, et al. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. J Neurol Neurosurg Psychiatry. 2018 Feb;89(2):127-137. doi: 10.1136/jnnp-2017-316880. Epub 2017 Nov 15.
(15) Hacohen Y, Wong YY, Lechner C, et al. Disease Course and Treatment Responses in Children With Relapsing Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease. JAMA Neurol. 2018 Apr 1;75(4):478-487. doi: 10.1001/jamaneurol.2017.4601.