Cell therapy evaluated in treatment-refractory rheumatoid arthritis

In a nonrandomized phase 1 study, all six patients with severe treatment-refractory rheumatoid arthritis who received CD19-targeted chimeric antigen receptor T cells (CAR T cells) showed improvement in disease activity. Remission was reported in three patients. However, all patients developed cytokine release syndrome (CRS), so clinical responses must be considered alongside the safety findings.

Published in Nature Medicine, the study is the phase 1 portion of the ongoing COMPARE phase 1/2 trial. The researchers evaluated the safety and efficacy of mivocabtagene autoleucel (miv-cel), an autologous CD19 CAR T-cell therapy. They also examined clinical changes associated with B-cell depletion and cellular and autoantibody responses. The treatment targets CD19; it cannot be described as an approach that selectively removes only autoreactive B cells.

Clinical responses and adverse events over 36–52 weeks of follow-up

The six participants, three men and three women, all tested positive for anti-citrullinated protein antibodies (ACPA). They stopped all disease-modifying antirheumatic drugs, received standard lymphodepleting conditioning, and then received a single dose of miv-cel. Safety and efficacy were followed for 36–52 weeks.

The primary endpoint was the incidence and severity of CRS, immune effector cell-associated neurotoxicity syndrome (ICANS), and adverse events during the first four weeks after infusion. All six patients developed grade 1–2 CRS. No ICANS or serious adverse events were reported, but one case of grade 3 aminotransferase elevation was recorded as a dose-limiting toxicity. It resolved without sequelae. The researchers judged that the primary endpoint had been met and that the safety results supported proceeding to phase 2.

Disease activity improved in every patient while they remained off immunosuppressive treatment. At the last follow-up, the median reduction in the 28-joint Disease Activity Score incorporating C-reactive protein (DAS28-CRP) was 34%. Remission according to DAS28-CRP criteria and an American College of Rheumatology 70% improvement response (ACR70) were each reported in three of the six patients. Improvement was observed in all participants, but not all reached remission.

CD19-positive B-cell depletion was observed in blood and tissue, alongside a sustained decline in autoantibodies. ACPA against modified citrullinated vimentin changed from positive to negative in four of six patients, while immunoglobulin M (IgM) rheumatoid factor did so in five of six. These antibody changes should be distinguished from regeneration of normal B cells or complete elimination of pathogenic B cells. Those latter outcomes were not reported in the provided abstract.

Early findings support further evaluation

This study presents evidence of short-term tolerability and a signal of clinical improvement with CD19 CAR T cells in patients whose disease was refractory to treatment. However, it was a nonrandomized phase 1 study of six participants, and the provided abstract contains no comparator-group results. These data alone cannot establish whether the treatment is superior to existing therapies, whether remission lasts for years, or how it affects joint damage and function.

The improvement in disease activity observed in all participants supports further evaluation. Adverse events, including CRS and aminotransferase elevation, also need to be considered. The researchers presented a rationale for proceeding to phase 2, but the abstract alone does not identify a comparator drug or confirm whether enrollment has begun. The study design and results were checked against the Europe PMC-indexed article abstract.