Rituximab

What it is

Rituximab is a monoclonal antibody, a medicine made to attach to a single target. It attaches to a protein called CD20 on B cells, the immune cells that mature into antibody-producing cells, and destroys them. In Europe, it is approved for some blood cancers, severe rheumatoid arthritis and other diseases in which B cells drive inflammation.¹

In psychiatry, it is used when autoimmune encephalitis (opens in a new tab) has not responded to the first treatments.² Researchers in Sweden are now testing whether it helps people with schizophrenia more broadly, on the idea that in some of them the immune system contributes to the illness.³

How well it works

The first study, in Sweden, gave a single infusion to 9 people with a schizophrenia-spectrum disorder that had not responded to treatment. Twelve weeks later, symptoms had fallen by at least 40% in 7 of them, and after 20 weeks in 4 of the 8 still assessed. The study had no comparison group, so it cannot show how much of the improvement came from the medicine.⁴ The people who improved more often had a particular pattern of activity in two kinds of immune cells, called Th1 and Th17 cells.⁵

A placebo-controlled trial, RCT-Rits, followed in Örebro. It gave 123 adults with psychosis a single infusion of rituximab or of salt water. Because symptom scores at the start were lower than expected, the main outcome was changed to the clinician’s rating of overall improvement.⁶ The trial is no longer recruiting, and its results have not been published.⁷ A second Swedish trial, in Uppsala, includes people with psychosis or obsessive-compulsive disorder and signs of immune involvement, by invitation.⁸

In England, the SINAPPS2 trial gives rituximab after intravenous immunoglobulin to people with psychosis and antibodies against nerve cells.⁹

Side effects

In the first Swedish study, rituximab was generally well tolerated, but a few people had a brief worsening of psychotic symptoms at first.⁴ Its main risks are infections, sometimes severe ones, especially in people over 65, and reactions during the infusion. Live vaccines are not given while B cells are low.²

Alternatives

Other medicines aimed at the immune system in schizophrenia include minocycline (opens in a new tab), prednisolone (opens in a new tab) and antibodies that block inflammation (opens in a new tab). None is an established treatment.

What we don’t know yet

• Whether rituximab helps more than placebo.
• Which people with schizophrenia, if any, have an illness driven by B cells, and how to recognise them.