Detailed description page of ThPDB2
| This page displays user query in tabular form. |
Th1468 details |
| Primary information | |
|---|---|
| ID | 14130 |
| Therapeutic ID | Th1468 |
| Protein Name | Tralokinumab |
| Sequence | >Th1468_Tralokinumab QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGLSWVRQAPGQGLEWMGWISANNGDTNYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK |
| Molecular Weight | 147000 |
| Chemical Formula | C6374H9822N1698O2014S44 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The half-life of tralokinumab is approximately 22 days.[L39287] |
| Description | Atopic dermatitis (AD) is an inflammatory skin disorder that causes skin inflammation, skin barrier dysfunction, and chronic pruritus.[A242432] It is estimated to affect up to 20% of adults and children worldwide, and is frequently associated with other atopic conditions such as asthma or allergic rhinitis. While AD is a heterogenous condition with a variety of apparent genetic and environmental causes,[A242422] it is primarily driven by the pro-inflammatory cytokine interleukin-13 (IL-13).[A242427] Tralokinumab is a fully human IgG4 monoclonal antibody targeted against IL-13. It neutralizes IL-13 activity by inhibiting its ability to bind with receptors, thus helping to alleviate AD symptoms. Tralokinumab was first approved for the treatment of atopic dermatitis by the EMA in June 2021, under the brand name Adtralza (Leo Pharma), and was subsequently approved in Canada in October 2021.[L39287] |
| Indication/Disease | Tralokinumab is indicated in Canada and the EU for the treatment of adult patients with moderate-to-severe atopic dermatitis who are candidates for systemic therapy and are inadequately controlled with topical interventions.[L39282,L39287] |
| Pharmacodynamics | Tralokinumab exerts its therapeutic effects by inhibiting the inflammatory cytokine (IL-13) primarily responsible for the pathogenesis of atopic dermatitis. It is administered subcutaneously with a loading dose of 600mg followed by a maintenance dose of 300mg every two weeks.[L39287] In clinical studies, tralokinumab treatment decreased the concentrations of a number of Th2 and Th22 immunity biomarkers in the blood, including periostin, IL-22, serum IgE. It also reduced epidermal thickness and decreased the expression of Keratin 16 and Ki-67 in skin affected by atopic dermatitis.[L39287] Hypersensitivity reactions, including anaphylaxis, have been reported following the use of tralokinumab.[L39287] Patients experiencing a systemic hypersensitivity reaction should discontinue treatment and initiate immediate therapy as clinically indicated. Tralokinumab should not be used in patients with pre-existing helminth infections, as the influence of tralokinumab on the immune response against helminth infections is unclear.[L39287] Patients with helminth infections should be treated prior to therapy with tralokinumab. Patients becoming infected during the course of therapy may be treated with anti-helminth medications, but should discontinue tralokinumab if the infection fails to resolve.[L39287] |
| Mechanism of Action | Interleukin-13 (IL-13) is a pro-inflammatory cytokine that has been implicated as the primary driver of atopic dermatitis (AD).[A242427] IL-13 binds with high affinity to both a heterodimeric form of IL-13Ra1 - complexed with IL-4Ra - and to IL-13Ra2, both of which are expressed on keratinocytes and fibroblasts.[A242432] While IL-13Ra2 does not appear to act as a signal mediator, the binding of IL-13 to heterodimeric IL-4Ra and IL-13Ra1 activates downstream Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) pathways which proceed to activate various signal transducer and activator of transcription (STAT) pathways.[A242432] STAT signalling induces the expression of periostin, an extracellular matrix protein which serves a number of physiological functions in addition to its pathogenic role in skin fibrosis and chronic allergic inflammation. IL-13 also appears to contribute to skin barrier dysfunction via an indirect downregulation of filaggrin (FLG), a structural protein essential for correct skin barrier functioning.[A242432] Tralokinumab is a monoclonal antibody targeted against IL-13. It neutralizes the activity of IL-13 by blocking its interaction with both the IL-13Ra1/IL-4Ra receptor complex and IL-13Ra2 receptors.[L39287] |
| Toxicity | There are no data regarding overdosage with tralokinumab. In clinical trials, intravenous doses up to 30 mg/kg and subcutaneous doses of 600mg every two weeks for 3 months were found to be well-tolerated.[L39282] In the event of a suspected overdose, patients should be administered supportive care as clinically indicated. |
| Metabolism | As with other therapeutic and endogenous proteins, the metabolism of tralokinumab is likely to occur via catabolism to smaller peptides and amino acids and has not been studied directly.[L39287] |
| Absorption | The absolute bioavailability of tralokinumab following subcutaneous administration is 76%, with a median Tmax of 5-8 days.[L39287] In clinical trials, steady-state serum concentrations were achieved by week 16 of treatment, with trough concentrations ranging from 98.0±41.1 mcg/mL to 101.4±42.7 mcg/mL.[L39287] |
| The volume of distribution of tralokinumab as estimated by population pharmacokinetic analysis was 4.2 L.[L39287] | |
| Clearance | The clearance of tralokinumab following subcutaneous administration was estimated to be 0.149 L/day.[L39282] |
| Categories | Amino Acids, Peptides, and Proteins |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interleukin-13 |
| Brand Name | Adtralza |
| Company | Leo Pharma |
| Brand Description | Leo Pharma |
| Prescribed For | Subcutaneous |
| Chemical Name | 150 mg |
| Formulation | NA |
| Physical Appearance | The most common side effects with Adtralza are upper respiratory tract infections (colds and other infections of the nose and throat) which may affect more than 1 in 10 people. Other common side effects include reactions at the injection site and redness and discomfort in the eye (which may affect up to 1 in 10 people). |
| Route of Administration | Adtralza was more effective than a placebo (dummy treatment) at reducing the extent and severity of atopic dermatitis after 16 weeks of treatment in three main studies in patients with moderate to severe disease that had not responded well enough to treatment applied to the skin. The main measures of effectiveness were having clear or almost clear skin, and a reduction in symptom score of at least 75%. |
| Recommended Dosage | Adtralza is a medicine for treating adults with moderate to severe atopic dermatitis (also known as eczema, when the skin is itchy, red and dry). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 14131 |
| Therapeutic ID | Th1468 |
| Protein Name | Tralokinumab |
| Sequence | >Th1468_Tralokinumab QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGLSWVRQAPGQGLEWMGWISANNGDTNYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK |
| Molecular Weight | 147000 |
| Chemical Formula | C6374H9822N1698O2014S44 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The half-life of tralokinumab is approximately 22 days.[L39287] |
| Description | Atopic dermatitis (AD) is an inflammatory skin disorder that causes skin inflammation, skin barrier dysfunction, and chronic pruritus.[A242432] It is estimated to affect up to 20% of adults and children worldwide, and is frequently associated with other atopic conditions such as asthma or allergic rhinitis. While AD is a heterogenous condition with a variety of apparent genetic and environmental causes,[A242422] it is primarily driven by the pro-inflammatory cytokine interleukin-13 (IL-13).[A242427] Tralokinumab is a fully human IgG4 monoclonal antibody targeted against IL-13. It neutralizes IL-13 activity by inhibiting its ability to bind with receptors, thus helping to alleviate AD symptoms. Tralokinumab was first approved for the treatment of atopic dermatitis by the EMA in June 2021, under the brand name Adtralza (Leo Pharma), and was subsequently approved in Canada in October 2021.[L39287] |
| Indication/Disease | Tralokinumab is indicated in Canada and the EU for the treatment of adult patients with moderate-to-severe atopic dermatitis who are candidates for systemic therapy and are inadequately controlled with topical interventions.[L39282,L39287] |
| Pharmacodynamics | Tralokinumab exerts its therapeutic effects by inhibiting the inflammatory cytokine (IL-13) primarily responsible for the pathogenesis of atopic dermatitis. It is administered subcutaneously with a loading dose of 600mg followed by a maintenance dose of 300mg every two weeks.[L39287] In clinical studies, tralokinumab treatment decreased the concentrations of a number of Th2 and Th22 immunity biomarkers in the blood, including periostin, IL-22, serum IgE. It also reduced epidermal thickness and decreased the expression of Keratin 16 and Ki-67 in skin affected by atopic dermatitis.[L39287] Hypersensitivity reactions, including anaphylaxis, have been reported following the use of tralokinumab.[L39287] Patients experiencing a systemic hypersensitivity reaction should discontinue treatment and initiate immediate therapy as clinically indicated. Tralokinumab should not be used in patients with pre-existing helminth infections, as the influence of tralokinumab on the immune response against helminth infections is unclear.[L39287] Patients with helminth infections should be treated prior to therapy with tralokinumab. Patients becoming infected during the course of therapy may be treated with anti-helminth medications, but should discontinue tralokinumab if the infection fails to resolve.[L39287] |
| Mechanism of Action | Interleukin-13 (IL-13) is a pro-inflammatory cytokine that has been implicated as the primary driver of atopic dermatitis (AD).[A242427] IL-13 binds with high affinity to both a heterodimeric form of IL-13Ra1 - complexed with IL-4Ra - and to IL-13Ra2, both of which are expressed on keratinocytes and fibroblasts.[A242432] While IL-13Ra2 does not appear to act as a signal mediator, the binding of IL-13 to heterodimeric IL-4Ra and IL-13Ra1 activates downstream Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) pathways which proceed to activate various signal transducer and activator of transcription (STAT) pathways.[A242432] STAT signalling induces the expression of periostin, an extracellular matrix protein which serves a number of physiological functions in addition to its pathogenic role in skin fibrosis and chronic allergic inflammation. IL-13 also appears to contribute to skin barrier dysfunction via an indirect downregulation of filaggrin (FLG), a structural protein essential for correct skin barrier functioning.[A242432] Tralokinumab is a monoclonal antibody targeted against IL-13. It neutralizes the activity of IL-13 by blocking its interaction with both the IL-13Ra1/IL-4Ra receptor complex and IL-13Ra2 receptors.[L39287] |
| Toxicity | There are no data regarding overdosage with tralokinumab. In clinical trials, intravenous doses up to 30 mg/kg and subcutaneous doses of 600mg every two weeks for 3 months were found to be well-tolerated.[L39282] In the event of a suspected overdose, patients should be administered supportive care as clinically indicated. |
| Metabolism | As with other therapeutic and endogenous proteins, the metabolism of tralokinumab is likely to occur via catabolism to smaller peptides and amino acids and has not been studied directly.[L39287] |
| Absorption | The absolute bioavailability of tralokinumab following subcutaneous administration is 76%, with a median Tmax of 5-8 days.[L39287] In clinical trials, steady-state serum concentrations were achieved by week 16 of treatment, with trough concentrations ranging from 98.0±41.1 mcg/mL to 101.4±42.7 mcg/mL.[L39287] |
| The volume of distribution of tralokinumab as estimated by population pharmacokinetic analysis was 4.2 L.[L39287] | |
| Clearance | The clearance of tralokinumab following subcutaneous administration was estimated to be 0.149 L/day.[L39282] |
| Categories | Antibodies |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interleukin-13 |
| Brand Name | Adtralza |
| Company | Leo Pharma |
| Brand Description | Leo Pharma |
| Prescribed For | Subcutaneous |
| Chemical Name | 150 mg / mL |
| Formulation | NA |
| Physical Appearance | The most common side effects with Adtralza are upper respiratory tract infections (colds and other infections of the nose and throat) which may affect more than 1 in 10 people. Other common side effects include reactions at the injection site and redness and discomfort in the eye (which may affect up to 1 in 10 people). |
| Route of Administration | Adtralza was more effective than a placebo (dummy treatment) at reducing the extent and severity of atopic dermatitis after 16 weeks of treatment in three main studies in patients with moderate to severe disease that had not responded well enough to treatment applied to the skin. The main measures of effectiveness were having clear or almost clear skin, and a reduction in symptom score of at least 75%. |
| Recommended Dosage | Adtralza is a medicine for treating adults with moderate to severe atopic dermatitis (also known as eczema, when the skin is itchy, red and dry). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 14132 |
| Therapeutic ID | Th1468 |
| Protein Name | Tralokinumab |
| Sequence | >Th1468_Tralokinumab QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGLSWVRQAPGQGLEWMGWISANNGDTNYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK |
| Molecular Weight | 147000 |
| Chemical Formula | C6374H9822N1698O2014S44 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The half-life of tralokinumab is approximately 22 days.[L39287] |
| Description | Atopic dermatitis (AD) is an inflammatory skin disorder that causes skin inflammation, skin barrier dysfunction, and chronic pruritus.[A242432] It is estimated to affect up to 20% of adults and children worldwide, and is frequently associated with other atopic conditions such as asthma or allergic rhinitis. While AD is a heterogenous condition with a variety of apparent genetic and environmental causes,[A242422] it is primarily driven by the pro-inflammatory cytokine interleukin-13 (IL-13).[A242427] Tralokinumab is a fully human IgG4 monoclonal antibody targeted against IL-13. It neutralizes IL-13 activity by inhibiting its ability to bind with receptors, thus helping to alleviate AD symptoms. Tralokinumab was first approved for the treatment of atopic dermatitis by the EMA in June 2021, under the brand name Adtralza (Leo Pharma), and was subsequently approved in Canada in October 2021.[L39287] |
| Indication/Disease | Tralokinumab is indicated in Canada and the EU for the treatment of adult patients with moderate-to-severe atopic dermatitis who are candidates for systemic therapy and are inadequately controlled with topical interventions.[L39282,L39287] |
| Pharmacodynamics | Tralokinumab exerts its therapeutic effects by inhibiting the inflammatory cytokine (IL-13) primarily responsible for the pathogenesis of atopic dermatitis. It is administered subcutaneously with a loading dose of 600mg followed by a maintenance dose of 300mg every two weeks.[L39287] In clinical studies, tralokinumab treatment decreased the concentrations of a number of Th2 and Th22 immunity biomarkers in the blood, including periostin, IL-22, serum IgE. It also reduced epidermal thickness and decreased the expression of Keratin 16 and Ki-67 in skin affected by atopic dermatitis.[L39287] Hypersensitivity reactions, including anaphylaxis, have been reported following the use of tralokinumab.[L39287] Patients experiencing a systemic hypersensitivity reaction should discontinue treatment and initiate immediate therapy as clinically indicated. Tralokinumab should not be used in patients with pre-existing helminth infections, as the influence of tralokinumab on the immune response against helminth infections is unclear.[L39287] Patients with helminth infections should be treated prior to therapy with tralokinumab. Patients becoming infected during the course of therapy may be treated with anti-helminth medications, but should discontinue tralokinumab if the infection fails to resolve.[L39287] |
| Mechanism of Action | Interleukin-13 (IL-13) is a pro-inflammatory cytokine that has been implicated as the primary driver of atopic dermatitis (AD).[A242427] IL-13 binds with high affinity to both a heterodimeric form of IL-13Ra1 - complexed with IL-4Ra - and to IL-13Ra2, both of which are expressed on keratinocytes and fibroblasts.[A242432] While IL-13Ra2 does not appear to act as a signal mediator, the binding of IL-13 to heterodimeric IL-4Ra and IL-13Ra1 activates downstream Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) pathways which proceed to activate various signal transducer and activator of transcription (STAT) pathways.[A242432] STAT signalling induces the expression of periostin, an extracellular matrix protein which serves a number of physiological functions in addition to its pathogenic role in skin fibrosis and chronic allergic inflammation. IL-13 also appears to contribute to skin barrier dysfunction via an indirect downregulation of filaggrin (FLG), a structural protein essential for correct skin barrier functioning.[A242432] Tralokinumab is a monoclonal antibody targeted against IL-13. It neutralizes the activity of IL-13 by blocking its interaction with both the IL-13Ra1/IL-4Ra receptor complex and IL-13Ra2 receptors.[L39287] |
| Toxicity | There are no data regarding overdosage with tralokinumab. In clinical trials, intravenous doses up to 30 mg/kg and subcutaneous doses of 600mg every two weeks for 3 months were found to be well-tolerated.[L39282] In the event of a suspected overdose, patients should be administered supportive care as clinically indicated. |
| Metabolism | As with other therapeutic and endogenous proteins, the metabolism of tralokinumab is likely to occur via catabolism to smaller peptides and amino acids and has not been studied directly.[L39287] |
| Absorption | The absolute bioavailability of tralokinumab following subcutaneous administration is 76%, with a median Tmax of 5-8 days.[L39287] In clinical trials, steady-state serum concentrations were achieved by week 16 of treatment, with trough concentrations ranging from 98.0±41.1 mcg/mL to 101.4±42.7 mcg/mL.[L39287] |
| The volume of distribution of tralokinumab as estimated by population pharmacokinetic analysis was 4.2 L.[L39287] | |
| Clearance | The clearance of tralokinumab following subcutaneous administration was estimated to be 0.149 L/day.[L39282] |
| Categories | Asthma, drug therapy |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interleukin-13 |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 14133 |
| Therapeutic ID | Th1468 |
| Protein Name | Tralokinumab |
| Sequence | >Th1468_Tralokinumab QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGLSWVRQAPGQGLEWMGWISANNGDTNYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK |
| Molecular Weight | 147000 |
| Chemical Formula | C6374H9822N1698O2014S44 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The half-life of tralokinumab is approximately 22 days.[L39287] |
| Description | Atopic dermatitis (AD) is an inflammatory skin disorder that causes skin inflammation, skin barrier dysfunction, and chronic pruritus.[A242432] It is estimated to affect up to 20% of adults and children worldwide, and is frequently associated with other atopic conditions such as asthma or allergic rhinitis. While AD is a heterogenous condition with a variety of apparent genetic and environmental causes,[A242422] it is primarily driven by the pro-inflammatory cytokine interleukin-13 (IL-13).[A242427] Tralokinumab is a fully human IgG4 monoclonal antibody targeted against IL-13. It neutralizes IL-13 activity by inhibiting its ability to bind with receptors, thus helping to alleviate AD symptoms. Tralokinumab was first approved for the treatment of atopic dermatitis by the EMA in June 2021, under the brand name Adtralza (Leo Pharma), and was subsequently approved in Canada in October 2021.[L39287] |
| Indication/Disease | Tralokinumab is indicated in Canada and the EU for the treatment of adult patients with moderate-to-severe atopic dermatitis who are candidates for systemic therapy and are inadequately controlled with topical interventions.[L39282,L39287] |
| Pharmacodynamics | Tralokinumab exerts its therapeutic effects by inhibiting the inflammatory cytokine (IL-13) primarily responsible for the pathogenesis of atopic dermatitis. It is administered subcutaneously with a loading dose of 600mg followed by a maintenance dose of 300mg every two weeks.[L39287] In clinical studies, tralokinumab treatment decreased the concentrations of a number of Th2 and Th22 immunity biomarkers in the blood, including periostin, IL-22, serum IgE. It also reduced epidermal thickness and decreased the expression of Keratin 16 and Ki-67 in skin affected by atopic dermatitis.[L39287] Hypersensitivity reactions, including anaphylaxis, have been reported following the use of tralokinumab.[L39287] Patients experiencing a systemic hypersensitivity reaction should discontinue treatment and initiate immediate therapy as clinically indicated. Tralokinumab should not be used in patients with pre-existing helminth infections, as the influence of tralokinumab on the immune response against helminth infections is unclear.[L39287] Patients with helminth infections should be treated prior to therapy with tralokinumab. Patients becoming infected during the course of therapy may be treated with anti-helminth medications, but should discontinue tralokinumab if the infection fails to resolve.[L39287] |
| Mechanism of Action | Interleukin-13 (IL-13) is a pro-inflammatory cytokine that has been implicated as the primary driver of atopic dermatitis (AD).[A242427] IL-13 binds with high affinity to both a heterodimeric form of IL-13Ra1 - complexed with IL-4Ra - and to IL-13Ra2, both of which are expressed on keratinocytes and fibroblasts.[A242432] While IL-13Ra2 does not appear to act as a signal mediator, the binding of IL-13 to heterodimeric IL-4Ra and IL-13Ra1 activates downstream Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) pathways which proceed to activate various signal transducer and activator of transcription (STAT) pathways.[A242432] STAT signalling induces the expression of periostin, an extracellular matrix protein which serves a number of physiological functions in addition to its pathogenic role in skin fibrosis and chronic allergic inflammation. IL-13 also appears to contribute to skin barrier dysfunction via an indirect downregulation of filaggrin (FLG), a structural protein essential for correct skin barrier functioning.[A242432] Tralokinumab is a monoclonal antibody targeted against IL-13. It neutralizes the activity of IL-13 by blocking its interaction with both the IL-13Ra1/IL-4Ra receptor complex and IL-13Ra2 receptors.[L39287] |
| Toxicity | There are no data regarding overdosage with tralokinumab. In clinical trials, intravenous doses up to 30 mg/kg and subcutaneous doses of 600mg every two weeks for 3 months were found to be well-tolerated.[L39282] In the event of a suspected overdose, patients should be administered supportive care as clinically indicated. |
| Metabolism | As with other therapeutic and endogenous proteins, the metabolism of tralokinumab is likely to occur via catabolism to smaller peptides and amino acids and has not been studied directly.[L39287] |
| Absorption | The absolute bioavailability of tralokinumab following subcutaneous administration is 76%, with a median Tmax of 5-8 days.[L39287] In clinical trials, steady-state serum concentrations were achieved by week 16 of treatment, with trough concentrations ranging from 98.0±41.1 mcg/mL to 101.4±42.7 mcg/mL.[L39287] |
| The volume of distribution of tralokinumab as estimated by population pharmacokinetic analysis was 4.2 L.[L39287] | |
| Clearance | The clearance of tralokinumab following subcutaneous administration was estimated to be 0.149 L/day.[L39282] |
| Categories | Blood Proteins |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interleukin-13 |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 14134 |
| Therapeutic ID | Th1468 |
| Protein Name | Tralokinumab |
| Sequence | >Th1468_Tralokinumab QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGLSWVRQAPGQGLEWMGWISANNGDTNYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK |
| Molecular Weight | 147000 |
| Chemical Formula | C6374H9822N1698O2014S44 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The half-life of tralokinumab is approximately 22 days.[L39287] |
| Description | Atopic dermatitis (AD) is an inflammatory skin disorder that causes skin inflammation, skin barrier dysfunction, and chronic pruritus.[A242432] It is estimated to affect up to 20% of adults and children worldwide, and is frequently associated with other atopic conditions such as asthma or allergic rhinitis. While AD is a heterogenous condition with a variety of apparent genetic and environmental causes,[A242422] it is primarily driven by the pro-inflammatory cytokine interleukin-13 (IL-13).[A242427] Tralokinumab is a fully human IgG4 monoclonal antibody targeted against IL-13. It neutralizes IL-13 activity by inhibiting its ability to bind with receptors, thus helping to alleviate AD symptoms. Tralokinumab was first approved for the treatment of atopic dermatitis by the EMA in June 2021, under the brand name Adtralza (Leo Pharma), and was subsequently approved in Canada in October 2021.[L39287] |
| Indication/Disease | Tralokinumab is indicated in Canada and the EU for the treatment of adult patients with moderate-to-severe atopic dermatitis who are candidates for systemic therapy and are inadequately controlled with topical interventions.[L39282,L39287] |
| Pharmacodynamics | Tralokinumab exerts its therapeutic effects by inhibiting the inflammatory cytokine (IL-13) primarily responsible for the pathogenesis of atopic dermatitis. It is administered subcutaneously with a loading dose of 600mg followed by a maintenance dose of 300mg every two weeks.[L39287] In clinical studies, tralokinumab treatment decreased the concentrations of a number of Th2 and Th22 immunity biomarkers in the blood, including periostin, IL-22, serum IgE. It also reduced epidermal thickness and decreased the expression of Keratin 16 and Ki-67 in skin affected by atopic dermatitis.[L39287] Hypersensitivity reactions, including anaphylaxis, have been reported following the use of tralokinumab.[L39287] Patients experiencing a systemic hypersensitivity reaction should discontinue treatment and initiate immediate therapy as clinically indicated. Tralokinumab should not be used in patients with pre-existing helminth infections, as the influence of tralokinumab on the immune response against helminth infections is unclear.[L39287] Patients with helminth infections should be treated prior to therapy with tralokinumab. Patients becoming infected during the course of therapy may be treated with anti-helminth medications, but should discontinue tralokinumab if the infection fails to resolve.[L39287] |
| Mechanism of Action | Interleukin-13 (IL-13) is a pro-inflammatory cytokine that has been implicated as the primary driver of atopic dermatitis (AD).[A242427] IL-13 binds with high affinity to both a heterodimeric form of IL-13Ra1 - complexed with IL-4Ra - and to IL-13Ra2, both of which are expressed on keratinocytes and fibroblasts.[A242432] While IL-13Ra2 does not appear to act as a signal mediator, the binding of IL-13 to heterodimeric IL-4Ra and IL-13Ra1 activates downstream Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) pathways which proceed to activate various signal transducer and activator of transcription (STAT) pathways.[A242432] STAT signalling induces the expression of periostin, an extracellular matrix protein which serves a number of physiological functions in addition to its pathogenic role in skin fibrosis and chronic allergic inflammation. IL-13 also appears to contribute to skin barrier dysfunction via an indirect downregulation of filaggrin (FLG), a structural protein essential for correct skin barrier functioning.[A242432] Tralokinumab is a monoclonal antibody targeted against IL-13. It neutralizes the activity of IL-13 by blocking its interaction with both the IL-13Ra1/IL-4Ra receptor complex and IL-13Ra2 receptors.[L39287] |
| Toxicity | There are no data regarding overdosage with tralokinumab. In clinical trials, intravenous doses up to 30 mg/kg and subcutaneous doses of 600mg every two weeks for 3 months were found to be well-tolerated.[L39282] In the event of a suspected overdose, patients should be administered supportive care as clinically indicated. |
| Metabolism | As with other therapeutic and endogenous proteins, the metabolism of tralokinumab is likely to occur via catabolism to smaller peptides and amino acids and has not been studied directly.[L39287] |
| Absorption | The absolute bioavailability of tralokinumab following subcutaneous administration is 76%, with a median Tmax of 5-8 days.[L39287] In clinical trials, steady-state serum concentrations were achieved by week 16 of treatment, with trough concentrations ranging from 98.0±41.1 mcg/mL to 101.4±42.7 mcg/mL.[L39287] |
| The volume of distribution of tralokinumab as estimated by population pharmacokinetic analysis was 4.2 L.[L39287] | |
| Clearance | The clearance of tralokinumab following subcutaneous administration was estimated to be 0.149 L/day.[L39282] |
| Categories | Globulins |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interleukin-13 |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 14135 |
| Therapeutic ID | Th1468 |
| Protein Name | Tralokinumab |
| Sequence | >Th1468_Tralokinumab QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGLSWVRQAPGQGLEWMGWISANNGDTNYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK |
| Molecular Weight | 147000 |
| Chemical Formula | C6374H9822N1698O2014S44 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The half-life of tralokinumab is approximately 22 days.[L39287] |
| Description | Atopic dermatitis (AD) is an inflammatory skin disorder that causes skin inflammation, skin barrier dysfunction, and chronic pruritus.[A242432] It is estimated to affect up to 20% of adults and children worldwide, and is frequently associated with other atopic conditions such as asthma or allergic rhinitis. While AD is a heterogenous condition with a variety of apparent genetic and environmental causes,[A242422] it is primarily driven by the pro-inflammatory cytokine interleukin-13 (IL-13).[A242427] Tralokinumab is a fully human IgG4 monoclonal antibody targeted against IL-13. It neutralizes IL-13 activity by inhibiting its ability to bind with receptors, thus helping to alleviate AD symptoms. Tralokinumab was first approved for the treatment of atopic dermatitis by the EMA in June 2021, under the brand name Adtralza (Leo Pharma), and was subsequently approved in Canada in October 2021.[L39287] |
| Indication/Disease | Tralokinumab is indicated in Canada and the EU for the treatment of adult patients with moderate-to-severe atopic dermatitis who are candidates for systemic therapy and are inadequately controlled with topical interventions.[L39282,L39287] |
| Pharmacodynamics | Tralokinumab exerts its therapeutic effects by inhibiting the inflammatory cytokine (IL-13) primarily responsible for the pathogenesis of atopic dermatitis. It is administered subcutaneously with a loading dose of 600mg followed by a maintenance dose of 300mg every two weeks.[L39287] In clinical studies, tralokinumab treatment decreased the concentrations of a number of Th2 and Th22 immunity biomarkers in the blood, including periostin, IL-22, serum IgE. It also reduced epidermal thickness and decreased the expression of Keratin 16 and Ki-67 in skin affected by atopic dermatitis.[L39287] Hypersensitivity reactions, including anaphylaxis, have been reported following the use of tralokinumab.[L39287] Patients experiencing a systemic hypersensitivity reaction should discontinue treatment and initiate immediate therapy as clinically indicated. Tralokinumab should not be used in patients with pre-existing helminth infections, as the influence of tralokinumab on the immune response against helminth infections is unclear.[L39287] Patients with helminth infections should be treated prior to therapy with tralokinumab. Patients becoming infected during the course of therapy may be treated with anti-helminth medications, but should discontinue tralokinumab if the infection fails to resolve.[L39287] |
| Mechanism of Action | Interleukin-13 (IL-13) is a pro-inflammatory cytokine that has been implicated as the primary driver of atopic dermatitis (AD).[A242427] IL-13 binds with high affinity to both a heterodimeric form of IL-13Ra1 - complexed with IL-4Ra - and to IL-13Ra2, both of which are expressed on keratinocytes and fibroblasts.[A242432] While IL-13Ra2 does not appear to act as a signal mediator, the binding of IL-13 to heterodimeric IL-4Ra and IL-13Ra1 activates downstream Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) pathways which proceed to activate various signal transducer and activator of transcription (STAT) pathways.[A242432] STAT signalling induces the expression of periostin, an extracellular matrix protein which serves a number of physiological functions in addition to its pathogenic role in skin fibrosis and chronic allergic inflammation. IL-13 also appears to contribute to skin barrier dysfunction via an indirect downregulation of filaggrin (FLG), a structural protein essential for correct skin barrier functioning.[A242432] Tralokinumab is a monoclonal antibody targeted against IL-13. It neutralizes the activity of IL-13 by blocking its interaction with both the IL-13Ra1/IL-4Ra receptor complex and IL-13Ra2 receptors.[L39287] |
| Toxicity | There are no data regarding overdosage with tralokinumab. In clinical trials, intravenous doses up to 30 mg/kg and subcutaneous doses of 600mg every two weeks for 3 months were found to be well-tolerated.[L39282] In the event of a suspected overdose, patients should be administered supportive care as clinically indicated. |
| Metabolism | As with other therapeutic and endogenous proteins, the metabolism of tralokinumab is likely to occur via catabolism to smaller peptides and amino acids and has not been studied directly.[L39287] |
| Absorption | The absolute bioavailability of tralokinumab following subcutaneous administration is 76%, with a median Tmax of 5-8 days.[L39287] In clinical trials, steady-state serum concentrations were achieved by week 16 of treatment, with trough concentrations ranging from 98.0±41.1 mcg/mL to 101.4±42.7 mcg/mL.[L39287] |
| The volume of distribution of tralokinumab as estimated by population pharmacokinetic analysis was 4.2 L.[L39287] | |
| Clearance | The clearance of tralokinumab following subcutaneous administration was estimated to be 0.149 L/day.[L39282] |
| Categories | Immunoglobulins |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interleukin-13 |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 14136 |
| Therapeutic ID | Th1468 |
| Protein Name | Tralokinumab |
| Sequence | >Th1468_Tralokinumab QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGLSWVRQAPGQGLEWMGWISANNGDTNYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK |
| Molecular Weight | 147000 |
| Chemical Formula | C6374H9822N1698O2014S44 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The half-life of tralokinumab is approximately 22 days.[L39287] |
| Description | Atopic dermatitis (AD) is an inflammatory skin disorder that causes skin inflammation, skin barrier dysfunction, and chronic pruritus.[A242432] It is estimated to affect up to 20% of adults and children worldwide, and is frequently associated with other atopic conditions such as asthma or allergic rhinitis. While AD is a heterogenous condition with a variety of apparent genetic and environmental causes,[A242422] it is primarily driven by the pro-inflammatory cytokine interleukin-13 (IL-13).[A242427] Tralokinumab is a fully human IgG4 monoclonal antibody targeted against IL-13. It neutralizes IL-13 activity by inhibiting its ability to bind with receptors, thus helping to alleviate AD symptoms. Tralokinumab was first approved for the treatment of atopic dermatitis by the EMA in June 2021, under the brand name Adtralza (Leo Pharma), and was subsequently approved in Canada in October 2021.[L39287] |
| Indication/Disease | Tralokinumab is indicated in Canada and the EU for the treatment of adult patients with moderate-to-severe atopic dermatitis who are candidates for systemic therapy and are inadequately controlled with topical interventions.[L39282,L39287] |
| Pharmacodynamics | Tralokinumab exerts its therapeutic effects by inhibiting the inflammatory cytokine (IL-13) primarily responsible for the pathogenesis of atopic dermatitis. It is administered subcutaneously with a loading dose of 600mg followed by a maintenance dose of 300mg every two weeks.[L39287] In clinical studies, tralokinumab treatment decreased the concentrations of a number of Th2 and Th22 immunity biomarkers in the blood, including periostin, IL-22, serum IgE. It also reduced epidermal thickness and decreased the expression of Keratin 16 and Ki-67 in skin affected by atopic dermatitis.[L39287] Hypersensitivity reactions, including anaphylaxis, have been reported following the use of tralokinumab.[L39287] Patients experiencing a systemic hypersensitivity reaction should discontinue treatment and initiate immediate therapy as clinically indicated. Tralokinumab should not be used in patients with pre-existing helminth infections, as the influence of tralokinumab on the immune response against helminth infections is unclear.[L39287] Patients with helminth infections should be treated prior to therapy with tralokinumab. Patients becoming infected during the course of therapy may be treated with anti-helminth medications, but should discontinue tralokinumab if the infection fails to resolve.[L39287] |
| Mechanism of Action | Interleukin-13 (IL-13) is a pro-inflammatory cytokine that has been implicated as the primary driver of atopic dermatitis (AD).[A242427] IL-13 binds with high affinity to both a heterodimeric form of IL-13Ra1 - complexed with IL-4Ra - and to IL-13Ra2, both of which are expressed on keratinocytes and fibroblasts.[A242432] While IL-13Ra2 does not appear to act as a signal mediator, the binding of IL-13 to heterodimeric IL-4Ra and IL-13Ra1 activates downstream Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) pathways which proceed to activate various signal transducer and activator of transcription (STAT) pathways.[A242432] STAT signalling induces the expression of periostin, an extracellular matrix protein which serves a number of physiological functions in addition to its pathogenic role in skin fibrosis and chronic allergic inflammation. IL-13 also appears to contribute to skin barrier dysfunction via an indirect downregulation of filaggrin (FLG), a structural protein essential for correct skin barrier functioning.[A242432] Tralokinumab is a monoclonal antibody targeted against IL-13. It neutralizes the activity of IL-13 by blocking its interaction with both the IL-13Ra1/IL-4Ra receptor complex and IL-13Ra2 receptors.[L39287] |
| Toxicity | There are no data regarding overdosage with tralokinumab. In clinical trials, intravenous doses up to 30 mg/kg and subcutaneous doses of 600mg every two weeks for 3 months were found to be well-tolerated.[L39282] In the event of a suspected overdose, patients should be administered supportive care as clinically indicated. |
| Metabolism | As with other therapeutic and endogenous proteins, the metabolism of tralokinumab is likely to occur via catabolism to smaller peptides and amino acids and has not been studied directly.[L39287] |
| Absorption | The absolute bioavailability of tralokinumab following subcutaneous administration is 76%, with a median Tmax of 5-8 days.[L39287] In clinical trials, steady-state serum concentrations were achieved by week 16 of treatment, with trough concentrations ranging from 98.0±41.1 mcg/mL to 101.4±42.7 mcg/mL.[L39287] |
| The volume of distribution of tralokinumab as estimated by population pharmacokinetic analysis was 4.2 L.[L39287] | |
| Clearance | The clearance of tralokinumab following subcutaneous administration was estimated to be 0.149 L/day.[L39282] |
| Categories | Immunoproteins |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interleukin-13 |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 14137 |
| Therapeutic ID | Th1468 |
| Protein Name | Tralokinumab |
| Sequence | >Th1468_Tralokinumab QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGLSWVRQAPGQGLEWMGWISANNGDTNYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK |
| Molecular Weight | 147000 |
| Chemical Formula | C6374H9822N1698O2014S44 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The half-life of tralokinumab is approximately 22 days.[L39287] |
| Description | Atopic dermatitis (AD) is an inflammatory skin disorder that causes skin inflammation, skin barrier dysfunction, and chronic pruritus.[A242432] It is estimated to affect up to 20% of adults and children worldwide, and is frequently associated with other atopic conditions such as asthma or allergic rhinitis. While AD is a heterogenous condition with a variety of apparent genetic and environmental causes,[A242422] it is primarily driven by the pro-inflammatory cytokine interleukin-13 (IL-13).[A242427] Tralokinumab is a fully human IgG4 monoclonal antibody targeted against IL-13. It neutralizes IL-13 activity by inhibiting its ability to bind with receptors, thus helping to alleviate AD symptoms. Tralokinumab was first approved for the treatment of atopic dermatitis by the EMA in June 2021, under the brand name Adtralza (Leo Pharma), and was subsequently approved in Canada in October 2021.[L39287] |
| Indication/Disease | Tralokinumab is indicated in Canada and the EU for the treatment of adult patients with moderate-to-severe atopic dermatitis who are candidates for systemic therapy and are inadequately controlled with topical interventions.[L39282,L39287] |
| Pharmacodynamics | Tralokinumab exerts its therapeutic effects by inhibiting the inflammatory cytokine (IL-13) primarily responsible for the pathogenesis of atopic dermatitis. It is administered subcutaneously with a loading dose of 600mg followed by a maintenance dose of 300mg every two weeks.[L39287] In clinical studies, tralokinumab treatment decreased the concentrations of a number of Th2 and Th22 immunity biomarkers in the blood, including periostin, IL-22, serum IgE. It also reduced epidermal thickness and decreased the expression of Keratin 16 and Ki-67 in skin affected by atopic dermatitis.[L39287] Hypersensitivity reactions, including anaphylaxis, have been reported following the use of tralokinumab.[L39287] Patients experiencing a systemic hypersensitivity reaction should discontinue treatment and initiate immediate therapy as clinically indicated. Tralokinumab should not be used in patients with pre-existing helminth infections, as the influence of tralokinumab on the immune response against helminth infections is unclear.[L39287] Patients with helminth infections should be treated prior to therapy with tralokinumab. Patients becoming infected during the course of therapy may be treated with anti-helminth medications, but should discontinue tralokinumab if the infection fails to resolve.[L39287] |
| Mechanism of Action | Interleukin-13 (IL-13) is a pro-inflammatory cytokine that has been implicated as the primary driver of atopic dermatitis (AD).[A242427] IL-13 binds with high affinity to both a heterodimeric form of IL-13Ra1 - complexed with IL-4Ra - and to IL-13Ra2, both of which are expressed on keratinocytes and fibroblasts.[A242432] While IL-13Ra2 does not appear to act as a signal mediator, the binding of IL-13 to heterodimeric IL-4Ra and IL-13Ra1 activates downstream Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) pathways which proceed to activate various signal transducer and activator of transcription (STAT) pathways.[A242432] STAT signalling induces the expression of periostin, an extracellular matrix protein which serves a number of physiological functions in addition to its pathogenic role in skin fibrosis and chronic allergic inflammation. IL-13 also appears to contribute to skin barrier dysfunction via an indirect downregulation of filaggrin (FLG), a structural protein essential for correct skin barrier functioning.[A242432] Tralokinumab is a monoclonal antibody targeted against IL-13. It neutralizes the activity of IL-13 by blocking its interaction with both the IL-13Ra1/IL-4Ra receptor complex and IL-13Ra2 receptors.[L39287] |
| Toxicity | There are no data regarding overdosage with tralokinumab. In clinical trials, intravenous doses up to 30 mg/kg and subcutaneous doses of 600mg every two weeks for 3 months were found to be well-tolerated.[L39282] In the event of a suspected overdose, patients should be administered supportive care as clinically indicated. |
| Metabolism | As with other therapeutic and endogenous proteins, the metabolism of tralokinumab is likely to occur via catabolism to smaller peptides and amino acids and has not been studied directly.[L39287] |
| Absorption | The absolute bioavailability of tralokinumab following subcutaneous administration is 76%, with a median Tmax of 5-8 days.[L39287] In clinical trials, steady-state serum concentrations were achieved by week 16 of treatment, with trough concentrations ranging from 98.0±41.1 mcg/mL to 101.4±42.7 mcg/mL.[L39287] |
| The volume of distribution of tralokinumab as estimated by population pharmacokinetic analysis was 4.2 L.[L39287] | |
| Clearance | The clearance of tralokinumab following subcutaneous administration was estimated to be 0.149 L/day.[L39282] |
| Categories | Proteins |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interleukin-13 |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 14138 |
| Therapeutic ID | Th1468 |
| Protein Name | Tralokinumab |
| Sequence | >Th1468_Tralokinumab QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGLSWVRQAPGQGLEWMGWISANNGDTNYGQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK |
| Molecular Weight | 147000 |
| Chemical Formula | C6374H9822N1698O2014S44 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The half-life of tralokinumab is approximately 22 days.[L39287] |
| Description | Atopic dermatitis (AD) is an inflammatory skin disorder that causes skin inflammation, skin barrier dysfunction, and chronic pruritus.[A242432] It is estimated to affect up to 20% of adults and children worldwide, and is frequently associated with other atopic conditions such as asthma or allergic rhinitis. While AD is a heterogenous condition with a variety of apparent genetic and environmental causes,[A242422] it is primarily driven by the pro-inflammatory cytokine interleukin-13 (IL-13).[A242427] Tralokinumab is a fully human IgG4 monoclonal antibody targeted against IL-13. It neutralizes IL-13 activity by inhibiting its ability to bind with receptors, thus helping to alleviate AD symptoms. Tralokinumab was first approved for the treatment of atopic dermatitis by the EMA in June 2021, under the brand name Adtralza (Leo Pharma), and was subsequently approved in Canada in October 2021.[L39287] |
| Indication/Disease | Tralokinumab is indicated in Canada and the EU for the treatment of adult patients with moderate-to-severe atopic dermatitis who are candidates for systemic therapy and are inadequately controlled with topical interventions.[L39282,L39287] |
| Pharmacodynamics | Tralokinumab exerts its therapeutic effects by inhibiting the inflammatory cytokine (IL-13) primarily responsible for the pathogenesis of atopic dermatitis. It is administered subcutaneously with a loading dose of 600mg followed by a maintenance dose of 300mg every two weeks.[L39287] In clinical studies, tralokinumab treatment decreased the concentrations of a number of Th2 and Th22 immunity biomarkers in the blood, including periostin, IL-22, serum IgE. It also reduced epidermal thickness and decreased the expression of Keratin 16 and Ki-67 in skin affected by atopic dermatitis.[L39287] Hypersensitivity reactions, including anaphylaxis, have been reported following the use of tralokinumab.[L39287] Patients experiencing a systemic hypersensitivity reaction should discontinue treatment and initiate immediate therapy as clinically indicated. Tralokinumab should not be used in patients with pre-existing helminth infections, as the influence of tralokinumab on the immune response against helminth infections is unclear.[L39287] Patients with helminth infections should be treated prior to therapy with tralokinumab. Patients becoming infected during the course of therapy may be treated with anti-helminth medications, but should discontinue tralokinumab if the infection fails to resolve.[L39287] |
| Mechanism of Action | Interleukin-13 (IL-13) is a pro-inflammatory cytokine that has been implicated as the primary driver of atopic dermatitis (AD).[A242427] IL-13 binds with high affinity to both a heterodimeric form of IL-13Ra1 - complexed with IL-4Ra - and to IL-13Ra2, both of which are expressed on keratinocytes and fibroblasts.[A242432] While IL-13Ra2 does not appear to act as a signal mediator, the binding of IL-13 to heterodimeric IL-4Ra and IL-13Ra1 activates downstream Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) pathways which proceed to activate various signal transducer and activator of transcription (STAT) pathways.[A242432] STAT signalling induces the expression of periostin, an extracellular matrix protein which serves a number of physiological functions in addition to its pathogenic role in skin fibrosis and chronic allergic inflammation. IL-13 also appears to contribute to skin barrier dysfunction via an indirect downregulation of filaggrin (FLG), a structural protein essential for correct skin barrier functioning.[A242432] Tralokinumab is a monoclonal antibody targeted against IL-13. It neutralizes the activity of IL-13 by blocking its interaction with both the IL-13Ra1/IL-4Ra receptor complex and IL-13Ra2 receptors.[L39287] |
| Toxicity | There are no data regarding overdosage with tralokinumab. In clinical trials, intravenous doses up to 30 mg/kg and subcutaneous doses of 600mg every two weeks for 3 months were found to be well-tolerated.[L39282] In the event of a suspected overdose, patients should be administered supportive care as clinically indicated. |
| Metabolism | As with other therapeutic and endogenous proteins, the metabolism of tralokinumab is likely to occur via catabolism to smaller peptides and amino acids and has not been studied directly.[L39287] |
| Absorption | The absolute bioavailability of tralokinumab following subcutaneous administration is 76%, with a median Tmax of 5-8 days.[L39287] In clinical trials, steady-state serum concentrations were achieved by week 16 of treatment, with trough concentrations ranging from 98.0±41.1 mcg/mL to 101.4±42.7 mcg/mL.[L39287] |
| The volume of distribution of tralokinumab as estimated by population pharmacokinetic analysis was 4.2 L.[L39287] | |
| Clearance | The clearance of tralokinumab following subcutaneous administration was estimated to be 0.149 L/day.[L39282] |
| Categories | Serum Globulins |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interleukin-13 |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |