Efficacy and safety of itolizumab, a novel anti-CD6 monoclonal antibody, in patients with moderate to severe chronic plaque psoriasis: Results of a double-blind, randomized, placebo-controlled, phase-III study

Krupashankar, DS; Dogra, Sunil; Kura, Mahendra M; Saraswat, Abir; Budamakuntla, Leelavathy; Sumathy, T K; Shah, Radha; Gopal, MG; Rao, T. Ramamohana; Srinivas, CR; Bhat, Ramesh M; Shetty, Neeta; Manmohan, G.; Krishna, Kotla Sai; Padmaja, Dalavoi; Pratap, D. V. S.; Garg, Vijay Kumar; Gupta, Sandesh; Pandey, Neeraj; Khopkar, Uday S; Montero, Enrique; Ramakrishnan, M. S.; Nair, Pradip; Ganapathi, P

doi:10.1016/j.jaad.2014.01.897

Cited by 93 publications

(112 citation statements)

References 20 publications

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“…It demonstrates the tolerability of itolizumab (up to 0.8 mg/kg weekly) with methotrexate in active RA over 24 weeks. This is consistent with the good safety profile of itolizumab monotherapy in RA patients dosed at up to 0.8 mg/kg once weekly [6] and in psoriasis patients dosed at up to 1.6 mg/kg every 2 weeks [8].…”

Section: Discussionsupporting

confidence: 85%

Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety and efficacy from a phase 2, randomized, open-label, parallel-group, dose-ranging study

Chopra¹,

Chandrashekara²,

Iyer

et al. 2015

Clin Rheumatol

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The objective of this study was to assess the safety and efficacy of itolizumab with methotrexate in active rheumatoid arthritis (RA) patients who had inadequate response to methotrexate. In this open-label, phase 2 study, 70 patients fulfilling American College of Rheumatology (ACR) criteria and negative for latent tuberculosis were randomized to four arms: 0.2, 0.4, or 0.8 mg/kg itolizumab weekly combined with oral methotrexate, and methotrexate alone (2:2:2:1). Patients were treated for 12 weeks, followed by 12 weeks of methotrexate alone during follow-up. Twelve weeks of itolizumab therapy was well tolerated. Forty-four patients reported adverse events (AEs); except for six severe AEs, all others were mild or moderate. Infusion-related reactions mainly occurred after the first infusion, and none were reported after the 11th infusion. No serum anti-itolizumab antibodies were detected. In the full analysis set, all itolizumab doses showed evidence of efficacy. At 12 weeks, 50 % of the patients achieved ACR20, and 58.3 % moderate or good 28-joint count Disease Activity Score (DAS-28) response; at week 24, these responses were seen in 22 and 31 patients. Significant improvements were seen in Short Form-36 Health Survey and Health Assessment Questionnaire Disability Index scores. Overall, itolizumab in combination with methotrexate was well tolerated and efficacious in RA for 12 weeks, with efficacy persisting for the entire 24-week evaluation period. (Clinical Trial Registry of India, http://ctri.nic.in/Clinicaltrials/login.php , CTRI/2008/091/000295).

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Section: Discussionsupporting

confidence: 85%

Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety and efficacy from a phase 2, randomized, open-label, parallel-group, dose-ranging study

Chopra¹,

Chandrashekara²,

Iyer

et al. 2015

Clin Rheumatol

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“…35 Studies have shown that itolizumab is not a T cell-depleting antibody when used as monotherapy both in Cuban RA 33 and psoriasis (unpublished data) patients. A small and transient decrease in ALC was, however, reported in an Indian study with psoriasis patients, 40 although no increase in infections was observed. In the present study, a transient decrease in the amount of T cells was also observed in RA patients.…”

Section: Discussionmentioning

confidence: 84%

“…25,38,39 Itolizumab, an anti-CD6 mAb, has demonstrated clinical benefits, 33,40 as well as modulation of T cell proliferation and decrease of proinflammatory cytokine levels in psoriasis patients. 35 Studies have shown that itolizumab is not a T cell-depleting antibody when used as monotherapy both in Cuban RA 33 and psoriasis (unpublished data) patients.…”

Section: Discussionmentioning

confidence: 99%

Immunological evaluation of rheumatoid arthritis patients treated with itolizumab

Aira

Hernández

Prada³

et al. 2015

mAbs

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(2016) Immunological evaluation of rheumatoid arthritis patients treated with itolizumab, mAbs, 8:1, 187-195, DOI: 10.1080/19420862.2015 To link to this article: https://doi.org/10. 1080/19420862.2015 Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical samples taken from 30 patients enrolled in a clinical trial. T and B cell subpopulations were measured at different time points of the study. Plasma cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. The combined treatment of itolizumab and methotrexate led to a reduction in the frequency of T cell subpopulations, and plasma levels of proinflammatory cytokines showed a significant decrease up to at least 12 weeks after treatment ended. No anti-idiotypic antibody response was detected. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease.

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“…The unexpected results that CD6 Ϫ/Ϫ mice were protected in the intestinal I/R-mediated injury demonstrated a previously unknown role of CD6 in the pathogenesis of this condition. CD6 was originally identified as a marker for T cells and has been associated with multiple autoimmune diseases including rheumatoid arthritis and psoriasis (42,43). Quantitative proteomics analysis of signalosome dynamics in T cells identifies CD6 as a Lat adaptor-independent TCR signaling hub, suggesting that CD6 modulates TCR signaling (44).…”

Section: Discussionmentioning

confidence: 99%

CD6 Receptor Regulates Intestinal Ischemia/Reperfusion-induced Injury by Modulating Natural IgM-producing B1a Cell Self-renewal

Enyindah-Asonye

Wei

et al. 2017

Journal of Biological Chemistry

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Edited by Luke O'NeillIntestinal ischemia/reperfusion (I/R) injury is a relatively common pathological condition that can lead to multi-organ failure and mortality. Regulatory mechanism for this disease is poorly understood, although it is established that circulating pathogenic natural IgM, which is primarily produced by B1a cells outside of the peritoneal cavity, are integrally involved. CD6 was originally identified as a marker for T cells and was later found to be present on some subsets of B cells in humans; however, whether CD6 plays any role in intestinal I/R-induced injury and, if so, the underlying mechanisms, remain unknown. Here we report that CD6؊/؊ mice were significantly protected from intestinal inflammation and mucosal damage compared with WT mice in a model of intestinal I/R-induced injury. Mechanistically, we found that CD6 was selectively expressed on B1 cells outside of the bone marrow and peritoneal cavity and that pathogenic natural IgM titers were reduced in the CD6 ؊/؊ mice in association with significantly decreased B1a cell population. Our results reveal an unexpected role of CD6 in the pathogenesis of intestinal IR-induced injury by regulating the self-renewal of B1a cells.

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Efficacy and safety of itolizumab, a novel anti-CD6 monoclonal antibody, in patients with moderate to severe chronic plaque psoriasis: Results of a double-blind, randomized, placebo-controlled, phase-III study

Cited by 93 publications

References 20 publications

Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety and efficacy from a phase 2, randomized, open-label, parallel-group, dose-ranging study

Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety and efficacy from a phase 2, randomized, open-label, parallel-group, dose-ranging study

Immunological evaluation of rheumatoid arthritis patients treated with itolizumab

CD6 Receptor Regulates Intestinal Ischemia/Reperfusion-induced Injury by Modulating Natural IgM-producing B1a Cell Self-renewal

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