Itolizumab – a humanized anti-CD6 monoclonal antibody with a better side effects profile for the treatment of psoriasis

Figures & data

Figure 1 The activation of naïve T-cells to different types of T-cells by APCs in the lymph node. Successful T-cell activation occurs in the presence of co-stimulatory signals.

Abbreviations: Ag, antigen; DCs, dendritic cells; HCs, histiocytes; KCs, keratinocytes; Ns, neutrophils; Ms, monocytes; APCs, antigen-presenting cells; TNF, tumor necrosis factor; IL, interleukin; Th, helper T-cell; TGF, transforming growth factor; T reg, T regulatory cells.

Figure 2 Types of T helper (Th) cells and pro-inflammatory cytokines responsible for major pathogenic events in psoriasis.

Abbreviations: IL, interleukin; TNF, tumor necrosis factor; IFN, interferon; VEGF, vascular endothelial growth factor; Th, helper T-cell.

Figure 3 Co-stimulatory signals between APCs and T-cells, and modulation at the CD6 level.

Abbreviations: APCs, antigen-presenting cells; ALCAM, activated leukocyte-cell adhesion molecule; ICAM, inter cellular adhesion molecule; LFA, lymphocyte function associated antigen; MHC, major histocompatibility complex; TCR, T-cell receptor.

Table 1 Adverse effects profile of Itolizumab

Common adverse effects encountered	Anand et al^Citation25 n=40(moderate–severe psoriasis)	Krupashankar et al^Citation26 n=225/52 weeks (moderate–severe psoriasis)	Rodriguez et al^Citation16 n=15/24 weeks (rheumatoid arthritis)
Infusion-related reaction	Chills, 5.69% Pyrexia, 4.88%	Acute, 17% Delayed, 3.6% Pyrexia, 8.5%	Headache, 73% Pyrexia, 60% Nausea, 46%
Pyrexia due to infections	ND	1.3% URTI, 7.6%	UTI, three patients
Pruritus	ND	5.4%	40%
Anti-drug antibody	One patient tested positive	15.7% no effect on safety and efficacy of drug	Transient and low levels
Effect on blood cells	ND	Small and transient decrease in mean absolute lymphocyte count	WBC count and absolute lymphocyte count within normal limits

Abbreviations: ND, no data; URTI, upper respiratory tract infection; UTI, urinary tract infection; WBC, white blood cell.

Table 2 Efficacy of Itolizumab in moderate to severe psoriasis cases

	Anand et al^Citation25 Phase II clinical trial	Krupashankar et al^Citation26 Phase III clinical trial
Mean PASI score at baseline	22.32±8.84	21.3±8.46
PASI-75 score at 12 weeks	45%	Arm A, 27% (A vs C, P=0.0172) Arm B, 36.4% (B vs C, P=0.043) Arm C (placebo), 2.3%
PGA score at 12 weeks (clear or minimal)	65%	A – 20% (A vs C, P<0.0001) B – 16% (B vs C, P<0.0002) C – 4.9%
Mean change from baseline PGA score at 12 weeks	P<0.0001	A vs C, P<0.0001 B vs C, P=0.0002
Mean change from baseline short form-36 at week 12	Improvement noted	A – 3.5±6.5 B – 2.4±6.8 C – 1.7±6.8
DLQI score at 12 weeks	Improvement noted	A – 7.3±6.6 B – 5.8±5.8 C – 9.0±7.9
Reduction from baseline in mean epidermal thickness at 12 weeks	P=0.0005	Improvement noted
Reduction from baseline in mean rate thickness at 12 weeks	P<0.0001	Improvement noted

Abbreviations: PASI, psoriasis area severity index; PGA, physician’s global assessment; DLQI, dermatology life quality index; vs, versus.

Table 3 Comparison of Itolizumab with different biologicals used for treating psoriasis

Drug	Study	N/dur in weeks	PASI-75, 12 weeks	Anti-drug antibodies	Incidence of infections
Alefacept	Ellis et al^Citation33	229/24	0.025 mg/kg, 33% 0.05 mg/kg, 31%	One patient
	Lebwohl et al^Citation34 (Phase III RDBPC)	507/24	15 mg, 33% 10 mg, 28%	4%	14%–16%
Adalimumab	Gordon et al^Citation35 (Phase II RDBPC)	147/60	–	Not reported	–
	Menter et al^Citation30 (Phase III RDBPC)	1,212/52	Alternate weeks therapy, 53% Weekly, 80%	8.8% associated decreased response	29%
	Gottileb et al^Citation36 (Phase II RDBPC)	112/24	30%	Not reported	URTI, 35% Sinusitis,14%
Etanercept	Tyring et al^Citation37 (Phase III RDBPC)	618/96	47.7%	18.3% No effect on safety and efficacy	103.9 events/100 patient years
	Leonardi et al^Citation38 (Extension of Phase III trial RDBPC)	652/24	25 mg biweekly, 34% 50 mg biweekly, 49%	Eight patients	URTI, 12%–14% Sinusitis, %–6%
Infliximab	Gottlieb et al^Citation39 (Phase II RDBPC trial)	249/30	Week 10: 3 mg/kg, 72% 5 mg/kg, 88%	3 mg/kg, 27% 5 mg/kg, 20%	–
	Menter et al^Citation40 (Phase III RDBPC trial)	835/50	Week 10: 3 mg/kg, 70% 5 mg/kg, 76%	3 mg/kg, 49% and 5 mg/kg, 39% associated decreased response	–
	Reich et al^Citation29 (Phase III RDBPC)	378/72	Week 10, 80%	27% associated decreased response	42%
Ustekinumab	Papp et al^Citation41 (Phase III RDBPC)	1,230/52	45 mg, 66.7% 90 mg, 75.7%	12.7%	31%
	Leonardi et al^Citation31 (Phase III RDBPC)	766/72	45 mg, 66.1% 90 mg, 66.4%	5.1%	21%
Itolizumab	Anand et al^Citation25 (Phase II RSB trial)	40/32	45%	One patient tested positive no effect on safety and efficacy	–
	Krupashankar et al^Citation26 (Phase III RDBPC)	225/52	Arm A 27% Arm B 36.4% Placebo 2.3%	15.7% no effect on safety and efficacy	18%

Abbreviations: N, number of patients; dur, duration of study; RDBPC, randomized, double-blind, placebo-controlled; RSB, randomized, single-blind; PASI, psoriasis area severity index; URTI, upper respiratory tract infection; –, data is not clearly mentioned.

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