Long-term efficacy and safety of itolizumab in patients with moderate-to-severe chronic plaque psoriasis: A double-blind, randomized-withdrawal, placebo-controlled study

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

doi:10.1016/j.jaad.2015.03.040

Cited by 26 publications

(21 citation statements)

References 6 publications

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“…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). A recent study using CD6-deficient mice found exacerbated collagen-induced arthritis in the CD6 Ϫ/Ϫ mice (45), a surprising result because anti-CD6 mAbs showed efficacy in treating patients with rheumatoid arthritis (46) and psoriasis (47). Compared with the debatable role of CD6 on T cells, information on the potential role of CD6 on B cells is even more limited.…”

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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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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“…Itolizumab is the first humanised IgG1 monoclonal antibody, which targets selectively CD6, a marker involved in co-stimulation, adhesion and maturation of T cells, which was tested in psoriasis. The treatment was proven effective in improving the PASI75 score in several RCTs of patients with psoriasis [ 66 , 67 ] and was licensed for use in India in 2013.…”

Section: Biologic Agentsmentioning

confidence: 99%

Tailored treatment options for patients with psoriatic arthritis and psoriasis: review of established and new biologic and small molecule therapies

2016

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The diverse clinical picture of PsA suggests the need to identify suitable therapies to address the different combinations of clinical manifestations. This review aimed to classify the available biologic agents and new small molecule inhibitors (licensed and nonlicensed) based on their proven efficacy in treating different clinical manifestations associated with psoriasis and PsA. This review presents the level of evidence of efficacy of different biologic treatments and small molecule inhibitors for certain clinical features of treatment of PsA and psoriasis, which was graded in categories I–IV. The literature searches were performed on the following classes of biologic agents and small molecules: TNF inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab), anti-IL12/IL23 (ustekinumab), anti-IL17 (secukinumab, brodalumab, ixekizumab), anti-IL6 (tocilizumab), T cell modulators (alefacept, efalizumab, abatacept, itolizumab), B cell depletion therapy (rituximab), phosphodiesterase 4 inhibitor (apremilast) and Janus kinase inhibitor (tofacitinib). A comprehensive table including 17 different biologic agents and small molecule inhibitors previously tested in psoriasis and PsA was generated, including the level of evidence of their efficacy for each of the clinical features included in our review (axial and peripheral arthritis, enthesitis, dactylitis, and nail and skin disease). We also proposed a limited set of recommendations for a sequential biologic treatment algorithm for patients with PsA who failed the first anti-TNF therapy, based on the available literature data. There is good evidence that many of the biologic treatments initially tested in psoriasis are also effective in PsA. Further research into both prognostic biomarkers and patient stratification is required to allow clinicians the possibility to make better use of the various biologic treatment options available. This review showed that there are many potentially new treatments that are not included in the current guidelines that can be used for selected categories of patients based on their disease phenotype, clinician experience and access to new biologic therapies.

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“…Results of the current study are in agreement with the published data on the safety of itolizumab. [78] Only 9 out of 155 patients experienced mild-to-moderate adverse events. Furthermore, no adverse events and infusion reactions were noted in patients who received itolizumab for the first 12 weeks and among those who completed the full regimen.…”

Section: Discussionmentioning

confidence: 99%

A real-world study to assess the effectiveness of itolizumab in patients with chronic plaque psoriasis

Parthasaradhi

Singh²,

Parasramani³

et al. 2017

Indian Dermatol Online J

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Background:While clinical trial data on the efficacy of itolizumab in the management of psoriasis is relatively well documented, data on the effectiveness of this humanized IgG1 monoclonal antibody in real-world settings is sparse.Aims:The current study assessed the effectiveness of itolizumab in real-world settings.Materials and Methods:This study assessed psoriasis area severity index (PASI), dermatology quality of life index (DLQI), safety, and tolerability data from a registry of itolizumab maintained by Syngene International, Bangalore. Registry data of 155 patients who were prescribed itolizumab at a dose of 1.6 mg/kg every 2 weeks for the first 12 weeks followed by 1.6 mg/kg every 4 weeks for up to 24 weeks for chronic plaque psoriasis.Results:In the study, 35.48% completed itolizumab for 12 weeks and 76.59% of these patients achieved PASI 75. Furthermore, 24.51% patients completed the full Itolizumab regimen for 24 weeks, of whom 92.01% patients achieved PASI 75. The mean percent change in DLQI scores at weeks 12 and 24 were 60.19 and 82.72, respectively. Adverse events and infusion reactions noted in the study were generally of mild to moderate severity.Conclusion:Itolizumab is a safe and effective option in treatment-compliant patients with chronic plaque psoriasis. Effects of putative compliance-modulators such as cost, route of administration, and delayed onset of action warrant further investigation.

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Long-term efficacy and safety of itolizumab in patients with moderate-to-severe chronic plaque psoriasis: A double-blind, randomized-withdrawal, placebo-controlled study

Cited by 26 publications

References 6 publications

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

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

Tailored treatment options for patients with psoriatic arthritis and psoriasis: review of established and new biologic and small molecule therapies

A real-world study to assess the effectiveness of itolizumab in patients with chronic plaque psoriasis

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