Myotonic disorders comprise both dystrophic myotonia and non-dystrophic myotonia. These conditions are caused by the mutation of specific genes which affect normal muscle function. The common feature that these conditions share is myotonia, during which muscles relax slowly and with difficulty after a voluntary contraction. This can cause stiffness, cramping, or an aching sensation in affected muscles, as well as muscle pain. Dystrophic myotonia is associated with muscle stiffness and systemic complications such as heart abnormalities which may be linked to sudden death, whereas non-dystrophic myotonia is mainly associated with muscle stiffness and muscle pain.
Mexiletine is under registration in Europe for the symptomatic treatment of myotonic disorders. It is administered as an oral capsule and it exerts its action by reducing the rate of contraction in the heart and other muscles. Currently it is used unlicensed in the UK, meaning that it is not currently approved but some healthcare providers consider it to be potentially beneficial based on research or professional experience. There are currently no licensed treatment options available to treat symptoms of myotonia, therefore, if licensed, mexiletine will offer access to an approved treatment option.
Upadacitinib acts by selectively blocking a protein called Janus-Associated Kinase 1 (JAK1 and JAK1/3). JAKs contribute to the processes within the cell to produce an immune or inflammatory response. There is an emerging body of evidence establishing that JAK dependent enzymes are major contributors to the progression of immunemediated diseases such as AS and that blocking such enzymes can be beneficial. Upadacitinib is taken orally and if licensed, it will offer an additional treatment option for patients with active AS.