Furthermore, anti-TNF treatment increased MRI activity and immune activation in several patients with primary progressive MS (PPMS) [152] and in patients with relapsing-remitting MS (RRMS), a phase II clinical study with a TNF inhibitor (Lenercept, a dimeric TNFR1 fused to the immunoglobulin (Ig)-G1 heavy chain) was discontinued because of unexpected exacerbations of the disease [153]. Here, TNFRSF1A is linked to primary progressive multiple sclerosis.