Immunobiologics:

targeted therapy against cytokines,cytokine receptors,and growth

factors
 immobiologics are drugs defined as antibodies and proteins engineered from
living organisms that induce or alter immune responses by interacting with
specific biologic targets.
 those used to treat skin disease and cancer are recombinant cytokines and growth
factors, monoclonal antibodies, and fusion proteins.
 Many cytokines are known to play critical roles in most common dermatologic
conditions, including psoriasis and atopic dermatitis.
Contraindications:

 The absolute contraindications

1. presence of active infections, more importantly, latent or active tuberculosis,
hepatitis B, C and HIV.
2. hypersensitivity
 Baseline investigations

CBC
Renal function test
Liver function test
Viral markers
CXR , PPD or IGRA for tuberculosis
Interleukin 1
IL-1 is a fundamental cytokine for directing epidermal responses to injury and
infection.
Stimuli include cell stress and infection
Once secreted, IL-1α and IL-1β have similar functions, both bind IL-1 receptor 1
(R1) on the surface on target cells, driving signal transduction.
acting on keratinocytes, fibroblasts, vascular endothelium, and lymphocyte,
inducing inflammatory and antimicrobial effects.
IL-1 signaling is also controlled by the expression of the IL-1 receptor antagonist
(IL-1Ra), which limits IL-1 receptor activation by competitive inhibition.

IL-1 also appears to be a key cytokine in the development of Th17 T-cell

responses.
ASSEMBLY OF INFLASOMME COMPLEXES IS CAUSED BY ACTIVATION OF IL-1B
A NUMBER OF STERILE AUTOINFLAMMATORY CONDITIONS ARE ASSOCIATED WITH
MUTATIONS IN GENES ENCODING INFLAMMASOME COMPONENTS, IN PARTICULAR, THE
CRYOPYRIN-ASSOCIATED PERIODIC SYNDROMES,
A COLLECTION OF DISEASES INCLUDING FAMILIAL COLD AUTOINFLAMMATORY
SYNDROME, MUCKLE-WELLS SYNDROME, AND NEONATAL-ONSET MULTISYSTEM
INFLAMMATORY DISORDER
PYRIN (MEFV) MUTATIONS ARE THE CAUSE OF FAMILIAL MEDITERRANEAN FEVER. AND
THE RECENTLY DESCRIBED DISEASE, PYRIN-ASSOCIATED AUTOINFLAMMATION WITH
NEUTROPHILIC DERMATOSIS

ELEVATED IL-1 ACTIVITY IS CAUSED BY A DEFICIENCY OF THE IL-1 RECEPTOR

ANTAGONIST,(DIRA) , THIS RESULTS IN PUSTULAR RASH, JOINT SWELLING, ORAL
MUCOSAL LESIONS, MULTIFOCAL OSTEOMYELITIS, AND PERIOSTITIS .
 1. ANAKINRA
 It is a recombinant, nonglycosylated version of IL-1Ra that competitively inhibits both
IL-1α and IL-1β activity at the IL-1 receptor.
 Anakinra has a short half-life of 4 to 6 hours and therefore requires
daily subcutaneous injections

 INDICATIONS:
 CAPS (FDA approved)
 Hidradenitis suppurativa
 deficiency of the IL-1 receptor antagonist
 pustular psoriasis

DOSAGE:
1-2 mg/kg SC qDay initially; may increase by 0.5- to 1-mg/kg increments to control active
inflammation, not to exceed 8 mg/kg/day
 2. Rilonacept
 Rilonacept is a dimeric fusion protein, functions as Soluble IL-1 decoy receptor binding IL-1α and IL-1b.

 INDICATION:
 cryopyrin-associated periodic syndromes, including familial cold autoinflammatory syndrome and Muckle-
Wells syndrome.
(Loading dose: 320 mg SC x 1 dose then Maintenance: 160 mg SC qWeek)

 DIRA
(4.4 mg/kg (not to exceed 320 mg) SC once weekly)
 3. Canakinumab

 Canakinumab is a fully human monoclonal IgG1 antibody that neutralizes IL-1β.

 FDA INDICATIONS :
 cryopyrin-associated periodic syndromes
( 150 mg SC q8wk)
 tumor necrosis factor receptor–associated periodic syndrome +
 hyperimmunoglobulin D syndrome/mevalonate kinase deficiency, and familial Mediterranean fever.
(150 mg SC q4wk; may increase to 300 mg q4wk if the clinical response is not adequate)
 INTERLEUKIN-18
 IL-18 is broadly expressed by epithelia, blood mononuclear cells, and
keratinocytes.
 Increased IL-18 expression is seen in acute atopic dermatitis and psoriasis, and
heightened responses of keratinocytes to IL-18 have been observed in cutaneous
lupus erythematosus lesions, thus roles for IL-18 in chronic or autoimmune
inflammatory skin conditions have been proposed.
 INTERLEUKIN-33

 IL-33 is an IL-1 family cytokine broadly expressed by endothelia and epithelia,

but typically absent from leukocytes.

 it is capable of promoting Th2 responses, disruptions in IL-33 or soluble ST2 (IL-

33R) expression have been linked with allergic inflammation, but there are no
ongoing clinical trials assessing the use of IL-33 or ST2.
 INTERLEUKIN-36

 The cytokines IL-3 is a member of the IL-1 superfamily.

 The 3 IL-36 cytokines are expressed primarily by epithelial tissues, including skin,
with IL-36α and IL-36β expression detectable only in inflamed skin, whereas IL-36γ
expression is present in normal skin
and strongly upregulated in inflammatory skin conditions, including psoriasis,
hidradenitis suppurativa, and pustular disease.
 The IL-36 cytokines are overexpressed in both chronic plaque and pustular psoriasis
skin lesions where they drive keratinocyte inflammatory responses.
 clinical trials of IL-36 receptor antagonists may be on the horizon in the near future.
 CYTOKINES OF THE TH17 AXIS
(IL-17A, IL-22, AND IL-23)
INTERLEUKIN-17
The homodimeric cytokine IL-17A is the signature cytokine of Th17 cells
IL-17A has wide-ranging proinflammatory effects and it induces the secretion of cytokines such as IL-6, IL-8, CCL20, and GM-CSF by
keratinocytes and fibroblasts, resulting in recruitment of T cells, macrophages, and neutrophils to the skin.
There are multiple cellular sources of IL-17A in the skin.

In psoriasis IL 17 expressed by mast cells , neutrophils and T-cells.

Around 50% of epidermal T cells are capable of secreting IL-17A.

variants in several genes involved in IL-17A responses are associated with increased genetic risk for psoriasis revealing critical roles for IL-
17A in psoriasis.
 SECUKINUMAB
Secukinumab is a fully human anti–IL-17A IgG1κ monoclonal antibody.

Indications:
Secukinumab rapidly improves both systemic and skin symptoms in GPP patients

FDA approved indications:

1.Moderate to severe plaque psoriasis 2.Hypertrophic palmoplantar psoriasis
3.Generalized pustular psoriasis 4.Psoriatic arthritis
5.Ankylosing spondylitis

Off-label uses:

1.Rheumatoid arthritis 2.Systemic lupus erythematosus

3. Familial Mediterranean fever
4.Tumor necrosis factor receptor-associated periodic syndrome (TRAPS )
 IXEKIZUMAB
 Ixekizumab is a humanized IgG4 monoclonal antibody that neutralizes IL-17A.

 ixekizumab 80 mg every 2 or 4 weeks, is effective for plaque psoriasis with more than 80% of patients
achieving PASI75 at 12 weeks .
 Ixekizumab is superior to the anti-TNF agent etanercept for plaque psoriasis and had beneficial effects on
scalp involvement, nail involvement, and itch .

FDA approved INDICATIONS:

1. Adults with moderate-to-severe plaque psoriasis (2016)
1. patients aged 6 years or older with moderate-to-severe plaque psoriasis who are candidates for systemic
therapy or phototherapy (2020)
2. adults with active psoriatic arthritis. (2017)
3. adults with active ankylosing spondylitis. (radiographic axial spondyloarthritis) (2019)
4. adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation. (2020)
 BRODALUMAB

 Brodalumab, is a human anti–IL-17RA monoclonal antibody targeting the IL-17 receptor A chain.
 INDICATIONS
FDA approved for moderateto-severe plaque psoriasis in adult patients who are
candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other
systemic therapies. ( 2016)
 INTERLEUKIN-22

IL-22 produced by natural killer (NK) cells and T cells.

 IL-22 has profound effects on epidermal keratinocytes, driving hyperplasia, keratinocyte
migration, and disruption of epidermal differentiation.
 IL-22, along with the other IL-20 subfamily members is abundantly overexpressed in lesional
psoriasis epidermis, as well as in the blood of psoriasis patients, and is restored back to normal
levels during effective treatments .

 A number of targeted IL-22/IL-22R therapeutics have been investigated for psoriasis

and atopic dermatitis, but There are no agents approved nor in ongoing trials for psoriasis.
 INTERLEUKIN-12

 IL-12 is a Th1 cytokine.

 IL-12 is a heterodimeric cytokine composed of IL-12p35 and IL-12p40 subunits.
 Activated antigen-presenting cells are the chief source of IL-12 and skin macrophages are the
main source of IL-12 in psoriasis, but the functional role of IL-12 in psoriasis is uncertain in
light of the dominance of the Th17 pathway in this disease.
 IL-12 expression is increased in psoriasis lesions and chronic, but not acute, atopic dermatitis
skin.
 USTEKINUMAB

 Ustekinumab is an IgG1κ human monoclonal antibody directed at IL-12p40 (the shared subunit of
IL-12 and IL-23).
 FDA APPROVED INDICATIONS:
1.moderate to severe plaque psoriasis in patients who are candidates for phototherapy or systemic
therapy.
(45 mg SC at Weeks 0 and 4, then q12weeks thereafter)

2. adults with active psoriatic arthritis alone or in combination with methotrexate.

3. Crohn disease and ulcerative colitis

 NTERLEUKIN-23

 IL-23 is a heterodimeric cytokine composed of 1 IL-23p19 and 1 IL-12p40 subunit.

 IL-23 is expressed by dendritic cells and epidermal keratinocytes.

 The importance of IL-23 in immune mediated inflammatory skin diseases stems from its
key functions as a master regulator of Th17 T-cell responses.

 Approaches targeting the IL-23 receptor itself are also in development.

 GUSELKUMAB

 a fully human IgG1λ antibody Specifically targeting the IL-23p19 subunit .

 FDA APPROVED INDICATIONS:

1.moderate-to-severe plaque psoriasis in adults who are candidates for systemic

therapy or phototherapy (2017)
(100 mg SC at Week 0, Week 4, and q8Weeks thereafter)

2. Active psoriatic arthritis (2020)

 TILDRAKIZUMAB

Tildrakizumab is a humanized monoclonal IgG1κ antibody targeting IL-23p19.

FDA approved indications:
1.moderate-to-severe plaque psoriasis in adults who are candidates for systemic
therapy or phototherapy.
(100 mg SC at Weeks 0, 4, and q12Weeks thereafter)
 RISANKIZUMAB

 Risankizumab is a fully human IgG1 monoclonal antibody against IL-23p19.

 FDA approved indications:

1.moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
(150 mg SC at Week 0, Week 4, and q12Weeks thereafter)

2. active psoriatic arthritis. (2020)

Thank you