The anti-CD6 antibody itolizumab provides clinical benefit without lymphopenia in rheumatoid arthritis patients: results from a 6-month, open-label Phase I clinical trial

Abstract

Itolizumab is a humanized anti-CD6 monoclonal antibody (mAb) that has previously shown encouraging results, in terms of safety and positive clinical effects, in a 6-week monotherapy clinical trial conducted in rheumatoid arthritis (RA) patients. The current Phase I study evaluated the safety and clinical response for a longer treatment of 12 itolizumab intravenous doses in subjects with active RA despite previous disease-modifying anti-rheumatic drug (DMARD) therapy. Twenty-one subjects were enrolled into four dosage groups (0·1, 0·2, 0·4 and 0·8 mg/kg). Efficacy end-points including American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates and disease activity score in 28 joints (DAS28) were monitored at baseline and at specific time-points during a 10-week follow-up period. Itolizumab was well tolerated up to the highest tested dose. No related serious adverse events were reported and most adverse events were mild. Remarkably, itolizumab treatment did not produce lymphopenia and, therefore, was not associated with infections. All patients achieved a clinical response (ACR20) at least once during the study. Eleven subjects (55%) achieved at least a 20% improvement in ACR just 1 week after the first itolizumab administration. The clinical response was observed from the beginning of the treatment and was sustained during 24 weeks. The efficacy profile of this 12-week treatment was similar to that of the previous study (6-week treatment). These results reinforce the safety profile of itolizumab and provide further evidence on the clinical benefit from the use of this anti-CD6 mAb in RA patients.

An Anti-CD6 Monoclonal Antibody (Itolizumab) Reduces Circulating IL-6 in Severe Covid-19 Elderly Patients

“…At the same time, itolizumab preserves the regulatory function of Treg cells and reduces T cell tra cking and in ltration at the in ammation sites [15]. The safety and e cacy of itolizumab in the treatment of patients with rheumatoid arthritis and severe chronic plaque psoriasis have been demonstrated in several clinical studies [28,29]. According to this, itolizumab become an alternative immunomodulatory intervention that seeks to control the T cell hyperactivated status in order to prevent such CRS.…”

Itolizumab, an anti-CD6 monoclonal antibody, as a potential treatment for COVID-19 complications

“…A randomized, open-label, phase 2 study conducted in India evaluated the safety and efficacy of Itolizumab in combination with methotrexate (MTX) in patients with active rheumatoid arthritis [22]. Itolizumab has been administered and was also found to be safe and efficacious in rheumatoid arthritis in trials performed in Cuba [23]. Additional trials ongoing in US and Australia are in acute graft versus host disease (aGVHD; Phase 1b/2 trial underway in US), uncontrolled asthma (Phase 1b trial in Australia), and lupus nephritis (Phase 1b trial in US).…”

An anti-CD6 monoclonal antibody (itolizumab) reduces circulating IL-6 in severe COVID-19 elderly patients

“…At the same time, itolizumab preserves the regulatory function of Treg cells and reduces T cell tra cking and in ltration at the in ammation sites [15]. The safety and e cacy of itolizumab in the treatment of patients with rheumatoid arthritis and severe chronic plaque psoriasis have been demonstrated in several clinical studies [30,31]. According to this, itolizumab become an alternative immunomodulatory intervention that seeks to control the T cell hyperactivated status in order to prevent such CRS.…”