Progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus, and that occurs only in patients who are immunocompromised, has affected an estimated 212 patients as of 2012, or 2.1 in every 1,000 using<unk> . It was first observed in seven patients who received<unk>  in late 2008; three cases were noted in clinical trials in 2006 leading to the drug being temporarily pulled from the market; two cases were reported to the FDA in August 2008; and two cases were announced in December 2008. By 21 January 2010 the FDA noted a total of 31 confirmed cases of PML, with the chance of developing the infection increasing as the number of infusions received by a patient increased. Because of this association, the drug label and package insert accompanying the drug will be updated to include this information. As of 29 February 2012, there were 212 confirmed cases of PML among 99,571 patients treated with<unk>  (2.1 cases per 1000 patients). All 54 patients with PML for whom samples were available before the diagnosis were positive for anti–JC virus antibodies. When the risk of PML was evaluated according to three risk factors, it was lowest among the patients who had used<unk>  for the shortest periods, those who had used few if any immunosuppressant drugs to treat MS in the past, and lastly who were negative for anti–JC virus antibodies. The incidence of PML in the low risk group was estimated to be 0.09 cases, or less, per 1000 patients. Patients who had taken<unk>  for longer, from 25 to 48 months, who were positive for anti–JC virus antibodies, had taken immunosuppressants before the initiation of<unk>  therapy had the highest risk of developing PML. Their risk is fully 123 times higher than the low risk group. (incidence, 11.1 cases per 1000 patients 95% CI, 8.3 to 14.5). While none of them had taken the drug in combination with other disease-modifying treatments, previous use of MS treatments increases the risk of PML between 3 and 4-fold. In 2016, EMA recommended all people taking<unk>  should undergo full MRI scans at least once a year due to concerns of progressive multifocal leukoencephalopathy (PML). In addition, more frequent MRI scans (e.g. every 3 to 6 months) should be performed using simplified protocols should be considered for those at higher risk of PML. Postmarketing surveillance in early 2008 revealed that 0.1% of people taking<unk>  experience clinically significant liver injury, leading to the FDA, EMEA and manufacturers recommending that the medication be discontinued in patients with jaundice or other evidence of significant liver damage. This rate is comparable to other immune-suppressing drugs. Evidence of hepatotoxicity in the form of elevated blood levels of bilirubin and liver enzymes can appear as soon as six days after an initial dose; reactions are unpredictable and may appear even if the patient does not react to previous treatment. Such signs reoccur upon rechallenge in some patients, indicating that damage is not coincidental. In the absence of any blockage these liver function tests are predictors of severe liver injury with possible sequelae of liver transplantation or death. Common adverse effects include fatigue and allergic reactions with a low risk of anaphylaxis, headache, nausea, colds and exacerbation of Crohn's disease in a minority of patients with the condition. Adolescents with Crohn's disease experience headache, fever and exacerbation of Crohn's disease.<unk>  is contraindicated for people with known hypersensitivity to the drug or its components and in patients with a history of PML (see interactions).<unk>  has also been linked to melanoma, though the association is unclear. The long-term effects of the drug are unknown and concern has been expressed over the risks of infection and cancer.<unk>  can increase the risk of infections, including the brain infection PML. PML is a very serious condition that may result in severe disability or death. The risk of PML increases the longer a person has been receiving<unk> , especially in people treated for more than two years. The risk is also higher for people who used medicines that suppress the immune system before starting<unk> , or if the person has antibodies against the virus that causes PML. About 6% of the people in studies developed long-lasting antibodies against<unk> , which reduced the medicine's effectiveness.
Natalizumab
Brolucizumab
Satralizumab
Ravulizumab
Mogamulizumab
Inebilizumab
Emicizumab
Ixekizumab