TELITACICEPT, A HUMAN RECOMBINANT FUSION PROTEIN TARGETING AND NEUTRALIZING B LYMPHOCYTE STIMULATOR (BLYS) AND A PROLIFERATION-INDUCING LIGAND (APRIL), IN RHEUMATOID ARTHRITIS (RA) PATIENTS WITH AN INADEQUATE RESPONSE TO METHOTREXATE (MTX): A RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY
Authors: Qing Zuraw et al.
This is a large randomized controlled trial from China with a novel mode of action in rheumatoid arthritis (RA). Telitacicept is a recombinant fusion protein neutralizing both BLyS and APRIL, – B-cell activating or proliferation-inducing factors -, which means this agent inhibit the development and survival of plasma cells and mature B cells. RA patients with inadequate responses to methotrexate were randomized to receive either telitacicept 160 mg or placebo once weekly for 24 weeks. Significantly more patients on telitacicept compared to placebo achieved an ACR20 response (60.0% vs 26.9%, P< 0.001), an ACR50 response (21.4% vs. 5.9%, P< 0.001), or an absence of radiographic progression (90.2% vs 66.4%, P< 0.001). But perhaps the most impressive information is the absence of serious adverse events (SAEs), with e.g. similar rates of infections between the telitacicept and the placebo group.
Over the past two decades, we have seen many innovative therapies being developed primarily in RA, and eventually being brought into other diseases. In recent years, the rate of new developments in RA has slowed down and so this new mode of action in RA is welcome. Telitacicept is an interesting compound on several levels: Firstly, this mode of action was first validated in lupus and is now secondarily applied to RA. Secondly, it is clearly a B-cell targeting agent, which works well in certain patients with RA, as we know from our experience with rituximab. Thirdly, it appears to have a better safety profile then rituximab, although I anticipate that European and American health authorities will insist on replicating the trial in Caucasian patients before approving it on the market. Finally, this compound is the result of Chinese research, which is certainly new in rheumatology at this level.