Itolizumab, a novel anti-CD6 monoclonal antibody: a safe and efficacious biologic agent for management of psoriasis
EXPERT OPINION ON BIOLOGICAL THERAPY
Authors: Dogra, Sunil; Uprety, Shraddha; Suresh, Swaroop Hassan
Abstract
Introduction: Psoriasis, a chronic immune-mediated skin disorder is associated with significant physical, psychological, and quality of life impairments. Along with well-documented genetic and environmental factors, immunological factors also contribute to the pathogenesis of psoriasis. Among the immunological factors, CD6 - dependent T-cell proliferation to form Th1 and Th17 cells play a major role in the pathogenesis of psoriasis. Itolizumab is the first humanized IgG1 monoclonal antibody, which selectively targets CD6.Areas covered: The current article presents the pharmacology of itolizumab and provides a review of the currently available data on the efficacy and safety of itolizumab for management of moderate to severe plaque psoriasis.Expert opinion: The use of biologics to attenuate the immune-mediated pathological events in psoriasis is a relatively well-established clinical practice. However, the safety and efficacy of biologics continues to be an unsettled topic of ongoing research. While available data seems to suggest that itolizumab may be a safer option, additional studies with higher sample sizes and active comparators are needed before definitive conclusions can be drawn on the place of itolizumab in the management of psoriasis.
Comparable outcome with T-cell-depleted unrelated-donor versus related-donor allogeneic bone marrow transplantation
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Authors: Alyea, EP; Weller, E; Fisher, DC; Freedman, AS; Gribben, YG; Lee, S; Schlossman, RL; Stone, RM; Friedberg, Y; DeAngelo, D; Liney, D; Windawi, S; Ng, A; Mauch, P; Antin, JH; Soiffer, RJ
Abstract
To assess the effect of related versus unrelated donors on outcomes in patients following T-cell-depleted (TCD) allogeneic BMT, we compared engraftment, GVHD, relapse rates, and survival in BMT patients who received CD6(+) TCD marrow from HLA-matched related donors (MRD) with those in patients who received CD6(+) TCD marrow from unrelated donors (URD). A total of 170 consecutive patients (120 with related donors, 50 with unrelated donors) were analyzed. The 2 groups were similar in age, sex, prior cytomegalovirus exposure, and stage of disease at the time of transplantation. GVHD prophylaxis was identical in the 2 groups, with TCD as the only method of GVHD prophylaxis. The total number of nucleated, CD34(+), CD3(+), and CD6(+) cells infused did not significantly differ between the 2 groups. The median day to reach 500 x 106 neutrophils/L was 12 days for both related (range, 8-22 days) and unrelated (range, 9-23 days) graft recipients (P = .92). Incidence of grades 2 through 4 acute GVHD was higher in URD than in MRD recipients (42% versus 20%, P = .004). According to multivariable analysis results, donor source was the single most important factor influencing GVHD (P = .01). The 2-year estimated risk of relapse was 45.9% in MRD recipients compared to 25.7% in URD recipients (P = .06). Multivariable Analysis revealed that the 2 most pertinent factors adversely affecting overall survival were advanced disease stage (P = .0002) and age greater than 50 years (P = .0003) at transplantation. There was no difference in relapse-free survival in URD and MRD recipients. We conclude that for patients undergoing TCD-BMT, use of unrelated marrow is associated with a higher risk of GVHD and other transplantation-related complications. However, these adverse events do not lead to inferior probability of relapse-free survival because they are accompanied by a reduction in relapse rates.