Although there are many systemic agents approved for treatment of psoriasis, getting patients clear of their psoriasis is still a hurdle. Secukinumab (Cosentyx) is the newest approved biologic medication (as of April 2015) for the treatment of moderate-to-severe psoriasis. It functions as an inhibitor of interleukin-17 (IL-17). Two other inhibitors of IL-17, brodalumab and ixekizumab, are currently undergoing clinical trials, but have yet to be approved by the FDA for treatment of psoriasis. In general, IL-17 inhibitors have a high efficacy, fast onset, and few known side effects.
Mechanism of Action
Secukinumab is a monoclonal antibody that selectively binds and neutralizes IL-17A, a pro-inflammatory cytokine implicated in the pathogenesis of psoriasis. IL-17A is 1 of 7 subtypes of the IL-17 family and is produced by helper T-17 cells (Th17). By binding free IL-17A, secukinumab prevents it from binding to its receptor and subsequently inhibits inflammation and epidermal changes in psoriasis including hyperkeratosis, acanthosis, and parakeratosis. Secukinumab also maintains the integrity of the skin barrier by preventing the down-regulation of filaggrin caused by IL-17A.
Dosing
The recommended dose for secu-kinumab is 300 mg by subcutaneous injection (given as 2 separate 1 mL injections of a 150 mg/mL formulation). It is administered weekly for the first 5 weeks and then once every 4 weeks thereafter. Secukinumab clearance is independent of the kidney and liver so no modification of the dose is needed for patients with renal or hepatic impairment.
Efficacy
Four phase 3 clinical trials have been conducted on secukinumab. Psoriasis Area and Severity Index (PASI 75) rates at 12 weeks averaged 75% to 87% and 67% to 87% for 300 mg and 150 mg secukinumab formulations, respectively. Modified Investigator’s Global Assessment (IGA) scores were between 62% to 73% and 51% to 53% for 300 mg and 150 mg secukinumab, respectively. PASI 75 rates and modified IGA success rates are 10% to 20% higher for the 300 mg compared with the 150 mg dose. Efficacy is higher with 300 mg compared to 150 mg independent of patient weight, so the 300 mg dose is recommended for all patients. Overdosage is unlikely, as doses of up to 3000 mg have been given intravenously without serious side effects. One phase 3 clinical trial compared both concentrations of secukinumab to etanercept (Enbrel). Secukinumab 300 mg was better at clearing skin than etanercept (PASI 75 rates of 77% for secukinumab 300 mg and 44% for etanercept 50 mg). In the CLEAR (Comparison to Assess Long-term Efficacy, Safety and Tolerability of Secukinumab vs Ustekinumab [Stelara]) trial, a head-to-head phase 3 trial comparing secukinumab to ustekinumab, secukinumab demonstrated superiority in achieving PASI 90 at week 16 (79.0% vs 57.6%, respectively; P<.0001) and PASI 75 at week 4 (44.3% vs 28.4%, respectively; P<.0001).
Side Effects
The most common side effects with secukinumab are increased risk of common mild infections, headache, eczema, pruritus, and diarrhea (Table 1). Infections are more common during the 12-week induction period than the maintenance period. The mechanism for increased common infections is not well-defined; it is possible that patients whose skin (and joint) disease has cleared spend more time in public and are simply exposed to more common infections.
There is an increased risk of Candida infections with IL-17 inhibition, which is dose dependent. All Candida infections in the secukinumab trials responded to standard treatment and did not necessitate drug discontinuation.
No systemic candidiasis infection, reactivation of latent tuberculosis (TB), or viral hepatitis were observed in any of the trials. While no cases of reactivated TB have been reported, screening for active and latent TB prior to starting secukinumab is recommended (Table 2).
Neutropenia is a rare side effect with secukinumab. The majority of cases of neutropenia were mild, transient, and reversible. Three cases of neutropenia were found in patients with nonserious infections including rhinitis, upper respiratory tract infections, and cystitis, though no cases resulted in drug discontinuation. As a precaution, a complete blood count should be performed if a patient on secukinumab presents with concerning symptoms or signs of infection.
Article continues on page 2
{{pagebreak}}
With other biologics such as adalimumab (Humira), the formation of antidrug antibodies (ADAs) could lead to a decrease in the efficacy of the drug. However, only 0.4% of patients in clinical trials developed ADAs to secukinumab. Furthermore, these antibodies did not lead to loss of efficacy or decreased drug concentration.
While a slight increase in serum transaminases was observed in patients on secukinumab, the majority of these cases were transient, resolving during the study. No cases of drug-induced liver injury were noted.
Secukinumab did not appear to increase the risk of solid tumors, lymphoma, leukemia, or skin cancer. Four patients developed malignant melanoma on secukinumab, but these individuals had several risk factors including prior exposure to phototherapy, tumor necrosis factor-alpha antagonist, or methotrexate use.
Hypersensitivity reactions can occur with secukinumab. Urticaria was the most common reaction. All cases of urticaria were nonserious and mild to moderate in severity.
Contraindications
Secukinumab should be used with caution in patients with Crohn’s disease. In prior studies, secukinumab was not effective at treating Crohn’s disease. In clinical trials for psoriasis, there were 3 patients who had flares of their Crohn’s disease out of over 3000 patients in those trials.
Live vaccines should not be given while on secukinumab (because there is no study showing they would be safe, not because they have been shown unsafe). If any live vaccines are needed, they should be given prior to initiating treatment with secukinumab. Nevertheless, a clinical study found no impact of secukinumab on antibody responses to killed influenza and meningococcal vaccinations.
Secukinumab is classified as pregnancy category B drug with no adverse effects on pregnancy in animal studies. There are no clinical trials of secukinumab in pregnant women. Secukinumab should only be used during pregnancy if the benefits outweigh the potential, unknown risks to the fetus. Because very little is known about the safety of secukinumab during pregnancy and nursing, caution should be exercised when prescribing secukinumab in these patients.
Monitoring
Due to the side effects of secukinumab, there are several recommended screening tests to perform in patients before and after they start secukinumab (Table 3). Because long-term data is not available for secukinumab, there are also several optional recommendations to prevent possible unknown long-term side effects.
Tips and Tricks
1. Ideal patients for secukinumab are those who have failed topical treatment, are interested in a biologic with the best chance at clearing their skin, and also are aware of the potential for possible, unforeseen long-term side effects due to lack of long-term studies.
2. Baseline TB test is recommended, however the mechanism of action of secukinumab is not expected to lead to an increased risk of tuberculosis.
3. Given the cost of this new drug, there are many opportunities available to help patients afford secukinumab. These options include a patient assistance foundation, a manufacturer’s coupon for free doses, and a $0 copay plan.
4. Deficiencies in the IL-17 pathway are associated with susceptibility to superficial Candida infections. Let patients know about the risk of yeast infection and that you can prescribe fluconazole if needed.
This article is an except from the book, Practical Psoriasis Management.
Dr. Culp is a fourth year medical student at Wake Forest School of Medicine.
Dr. Farhangian is a fourth year medical student at SUNY Downstate College of Medicine in Brooklyn, NY.
Dr. Feldman is with the Center for Dermatology Research and the Departments of Dermatology, Pathology and Public Health Sciences at Wake Forest University School of Medicine in Winston-Salem, NC.
Disclosure: The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, L.P. Dr. Feldman is a consultant and speaker for Galderma, Stiefel/GlaxoSmithKline, Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Genentech, BiogenIdec, and Bristol-Myers Squibb. Dr. Feldman has received grants from Galderma, Astellas, Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Genentech, BiogenIdec, Coria/Valeant, Pharmaderm, Ortho Pharmaceuticals, Aventis Pharmaceuticals, Roche Dermatology, 3M, Bristol-Myers Squibb, Stiefel/GlaxoSmithKline, Novartis, Medicis, Leo, HanAll Pharmaceuticals, Celgene, Basilea, and Anacor and has received stock options from Photomedex. He is owner of www.DrScore.com and a founder of Causa Research.
Disclosure: The authors report no relevant financial relationships.
Suggested References
1. Blauvelt A, Prinz JC, Gottlieb AB, et al. Secukinumab administration by pre-filled syringe: Efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol. 2015;172(2):484-493.
2. Gooderham M, Posso-De Los Rios CJ, Rubio-Gomez, GA, Papp K. Interleukin-17 (Il-17) inhibitors in the treatment of plaque psoriasis: A review. Skin Therapy Lett. 2015;20(1):1-5.
3. Yamauchi PS, Bagel J. Next-generation biologics in the management of plaque psoriasis: A literature review of IL-17 inhibition. J Drugs Dermatol. 2015;14(3):244-250.
4. Ohtsuki M, Morita A, Abe M, et al. Secukinumab efficacy and safety in Japanese patients with moderate-to-severe plaque psoriasis: Subanalysis from ERASURE, a randomized, placebo-controlled, phase 3 study. J Dermatol. 2014;41(12):1039-1046.
5. Paul C, Lacour JP, Kreutzer K, et al. Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol. 2015;29(6):1082-1090.
6. Sanford M, McKeage K. Secukinumab: first global approval. Drugs. 2015;75(3):329-338.
7. Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis-results of two phase 3 trials. N Engl J Med. 2014;371(4):326-338.
8. Colombel JF, Sendid B, Jouault T, Poulain D. Secukinumab failure in Crohn’s disease: the yeast connection? Gut. 2013;62(5):800-801.
Although there are many systemic agents approved for treatment of psoriasis, getting patients clear of their psoriasis is still a hurdle. Secukinumab (Cosentyx) is the newest approved biologic medication (as of April 2015) for the treatment of moderate-to-severe psoriasis. It functions as an inhibitor of interleukin-17 (IL-17). Two other inhibitors of IL-17, brodalumab and ixekizumab, are currently undergoing clinical trials, but have yet to be approved by the FDA for treatment of psoriasis. In general, IL-17 inhibitors have a high efficacy, fast onset, and few known side effects.
Mechanism of Action
Secukinumab is a monoclonal antibody that selectively binds and neutralizes IL-17A, a pro-inflammatory cytokine implicated in the pathogenesis of psoriasis. IL-17A is 1 of 7 subtypes of the IL-17 family and is produced by helper T-17 cells (Th17). By binding free IL-17A, secukinumab prevents it from binding to its receptor and subsequently inhibits inflammation and epidermal changes in psoriasis including hyperkeratosis, acanthosis, and parakeratosis. Secukinumab also maintains the integrity of the skin barrier by preventing the down-regulation of filaggrin caused by IL-17A.
Dosing
The recommended dose for secu-kinumab is 300 mg by subcutaneous injection (given as 2 separate 1 mL injections of a 150 mg/mL formulation). It is administered weekly for the first 5 weeks and then once every 4 weeks thereafter. Secukinumab clearance is independent of the kidney and liver so no modification of the dose is needed for patients with renal or hepatic impairment.
Efficacy
Four phase 3 clinical trials have been conducted on secukinumab. Psoriasis Area and Severity Index (PASI 75) rates at 12 weeks averaged 75% to 87% and 67% to 87% for 300 mg and 150 mg secukinumab formulations, respectively. Modified Investigator’s Global Assessment (IGA) scores were between 62% to 73% and 51% to 53% for 300 mg and 150 mg secukinumab, respectively. PASI 75 rates and modified IGA success rates are 10% to 20% higher for the 300 mg compared with the 150 mg dose. Efficacy is higher with 300 mg compared to 150 mg independent of patient weight, so the 300 mg dose is recommended for all patients. Overdosage is unlikely, as doses of up to 3000 mg have been given intravenously without serious side effects. One phase 3 clinical trial compared both concentrations of secukinumab to etanercept (Enbrel). Secukinumab 300 mg was better at clearing skin than etanercept (PASI 75 rates of 77% for secukinumab 300 mg and 44% for etanercept 50 mg). In the CLEAR (Comparison to Assess Long-term Efficacy, Safety and Tolerability of Secukinumab vs Ustekinumab [Stelara]) trial, a head-to-head phase 3 trial comparing secukinumab to ustekinumab, secukinumab demonstrated superiority in achieving PASI 90 at week 16 (79.0% vs 57.6%, respectively; P<.0001) and PASI 75 at week 4 (44.3% vs 28.4%, respectively; P<.0001).
Side Effects
The most common side effects with secukinumab are increased risk of common mild infections, headache, eczema, pruritus, and diarrhea (Table 1). Infections are more common during the 12-week induction period than the maintenance period. The mechanism for increased common infections is not well-defined; it is possible that patients whose skin (and joint) disease has cleared spend more time in public and are simply exposed to more common infections.
There is an increased risk of Candida infections with IL-17 inhibition, which is dose dependent. All Candida infections in the secukinumab trials responded to standard treatment and did not necessitate drug discontinuation.
No systemic candidiasis infection, reactivation of latent tuberculosis (TB), or viral hepatitis were observed in any of the trials. While no cases of reactivated TB have been reported, screening for active and latent TB prior to starting secukinumab is recommended (Table 2).
Neutropenia is a rare side effect with secukinumab. The majority of cases of neutropenia were mild, transient, and reversible. Three cases of neutropenia were found in patients with nonserious infections including rhinitis, upper respiratory tract infections, and cystitis, though no cases resulted in drug discontinuation. As a precaution, a complete blood count should be performed if a patient on secukinumab presents with concerning symptoms or signs of infection.
Article continues on page 2
{{pagebreak}}
With other biologics such as adalimumab (Humira), the formation of antidrug antibodies (ADAs) could lead to a decrease in the efficacy of the drug. However, only 0.4% of patients in clinical trials developed ADAs to secukinumab. Furthermore, these antibodies did not lead to loss of efficacy or decreased drug concentration.
While a slight increase in serum transaminases was observed in patients on secukinumab, the majority of these cases were transient, resolving during the study. No cases of drug-induced liver injury were noted.
Secukinumab did not appear to increase the risk of solid tumors, lymphoma, leukemia, or skin cancer. Four patients developed malignant melanoma on secukinumab, but these individuals had several risk factors including prior exposure to phototherapy, tumor necrosis factor-alpha antagonist, or methotrexate use.
Hypersensitivity reactions can occur with secukinumab. Urticaria was the most common reaction. All cases of urticaria were nonserious and mild to moderate in severity.
Contraindications
Secukinumab should be used with caution in patients with Crohn’s disease. In prior studies, secukinumab was not effective at treating Crohn’s disease. In clinical trials for psoriasis, there were 3 patients who had flares of their Crohn’s disease out of over 3000 patients in those trials.
Live vaccines should not be given while on secukinumab (because there is no study showing they would be safe, not because they have been shown unsafe). If any live vaccines are needed, they should be given prior to initiating treatment with secukinumab. Nevertheless, a clinical study found no impact of secukinumab on antibody responses to killed influenza and meningococcal vaccinations.
Secukinumab is classified as pregnancy category B drug with no adverse effects on pregnancy in animal studies. There are no clinical trials of secukinumab in pregnant women. Secukinumab should only be used during pregnancy if the benefits outweigh the potential, unknown risks to the fetus. Because very little is known about the safety of secukinumab during pregnancy and nursing, caution should be exercised when prescribing secukinumab in these patients.
Monitoring
Due to the side effects of secukinumab, there are several recommended screening tests to perform in patients before and after they start secukinumab (Table 3). Because long-term data is not available for secukinumab, there are also several optional recommendations to prevent possible unknown long-term side effects.
Tips and Tricks
1. Ideal patients for secukinumab are those who have failed topical treatment, are interested in a biologic with the best chance at clearing their skin, and also are aware of the potential for possible, unforeseen long-term side effects due to lack of long-term studies.
2. Baseline TB test is recommended, however the mechanism of action of secukinumab is not expected to lead to an increased risk of tuberculosis.
3. Given the cost of this new drug, there are many opportunities available to help patients afford secukinumab. These options include a patient assistance foundation, a manufacturer’s coupon for free doses, and a $0 copay plan.
4. Deficiencies in the IL-17 pathway are associated with susceptibility to superficial Candida infections. Let patients know about the risk of yeast infection and that you can prescribe fluconazole if needed.
This article is an except from the book, Practical Psoriasis Management.
Dr. Culp is a fourth year medical student at Wake Forest School of Medicine.
Dr. Farhangian is a fourth year medical student at SUNY Downstate College of Medicine in Brooklyn, NY.
Dr. Feldman is with the Center for Dermatology Research and the Departments of Dermatology, Pathology and Public Health Sciences at Wake Forest University School of Medicine in Winston-Salem, NC.
Disclosure: The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, L.P. Dr. Feldman is a consultant and speaker for Galderma, Stiefel/GlaxoSmithKline, Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Genentech, BiogenIdec, and Bristol-Myers Squibb. Dr. Feldman has received grants from Galderma, Astellas, Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Genentech, BiogenIdec, Coria/Valeant, Pharmaderm, Ortho Pharmaceuticals, Aventis Pharmaceuticals, Roche Dermatology, 3M, Bristol-Myers Squibb, Stiefel/GlaxoSmithKline, Novartis, Medicis, Leo, HanAll Pharmaceuticals, Celgene, Basilea, and Anacor and has received stock options from Photomedex. He is owner of www.DrScore.com and a founder of Causa Research.
Disclosure: The authors report no relevant financial relationships.
Suggested References
1. Blauvelt A, Prinz JC, Gottlieb AB, et al. Secukinumab administration by pre-filled syringe: Efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol. 2015;172(2):484-493.
2. Gooderham M, Posso-De Los Rios CJ, Rubio-Gomez, GA, Papp K. Interleukin-17 (Il-17) inhibitors in the treatment of plaque psoriasis: A review. Skin Therapy Lett. 2015;20(1):1-5.
3. Yamauchi PS, Bagel J. Next-generation biologics in the management of plaque psoriasis: A literature review of IL-17 inhibition. J Drugs Dermatol. 2015;14(3):244-250.
4. Ohtsuki M, Morita A, Abe M, et al. Secukinumab efficacy and safety in Japanese patients with moderate-to-severe plaque psoriasis: Subanalysis from ERASURE, a randomized, placebo-controlled, phase 3 study. J Dermatol. 2014;41(12):1039-1046.
5. Paul C, Lacour JP, Kreutzer K, et al. Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol. 2015;29(6):1082-1090.
6. Sanford M, McKeage K. Secukinumab: first global approval. Drugs. 2015;75(3):329-338.
7. Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis-results of two phase 3 trials. N Engl J Med. 2014;371(4):326-338.
8. Colombel JF, Sendid B, Jouault T, Poulain D. Secukinumab failure in Crohn’s disease: the yeast connection? Gut. 2013;62(5):800-801.
Although there are many systemic agents approved for treatment of psoriasis, getting patients clear of their psoriasis is still a hurdle. Secukinumab (Cosentyx) is the newest approved biologic medication (as of April 2015) for the treatment of moderate-to-severe psoriasis. It functions as an inhibitor of interleukin-17 (IL-17). Two other inhibitors of IL-17, brodalumab and ixekizumab, are currently undergoing clinical trials, but have yet to be approved by the FDA for treatment of psoriasis. In general, IL-17 inhibitors have a high efficacy, fast onset, and few known side effects.
Mechanism of Action
Secukinumab is a monoclonal antibody that selectively binds and neutralizes IL-17A, a pro-inflammatory cytokine implicated in the pathogenesis of psoriasis. IL-17A is 1 of 7 subtypes of the IL-17 family and is produced by helper T-17 cells (Th17). By binding free IL-17A, secukinumab prevents it from binding to its receptor and subsequently inhibits inflammation and epidermal changes in psoriasis including hyperkeratosis, acanthosis, and parakeratosis. Secukinumab also maintains the integrity of the skin barrier by preventing the down-regulation of filaggrin caused by IL-17A.
Dosing
The recommended dose for secu-kinumab is 300 mg by subcutaneous injection (given as 2 separate 1 mL injections of a 150 mg/mL formulation). It is administered weekly for the first 5 weeks and then once every 4 weeks thereafter. Secukinumab clearance is independent of the kidney and liver so no modification of the dose is needed for patients with renal or hepatic impairment.
Efficacy
Four phase 3 clinical trials have been conducted on secukinumab. Psoriasis Area and Severity Index (PASI 75) rates at 12 weeks averaged 75% to 87% and 67% to 87% for 300 mg and 150 mg secukinumab formulations, respectively. Modified Investigator’s Global Assessment (IGA) scores were between 62% to 73% and 51% to 53% for 300 mg and 150 mg secukinumab, respectively. PASI 75 rates and modified IGA success rates are 10% to 20% higher for the 300 mg compared with the 150 mg dose. Efficacy is higher with 300 mg compared to 150 mg independent of patient weight, so the 300 mg dose is recommended for all patients. Overdosage is unlikely, as doses of up to 3000 mg have been given intravenously without serious side effects. One phase 3 clinical trial compared both concentrations of secukinumab to etanercept (Enbrel). Secukinumab 300 mg was better at clearing skin than etanercept (PASI 75 rates of 77% for secukinumab 300 mg and 44% for etanercept 50 mg). In the CLEAR (Comparison to Assess Long-term Efficacy, Safety and Tolerability of Secukinumab vs Ustekinumab [Stelara]) trial, a head-to-head phase 3 trial comparing secukinumab to ustekinumab, secukinumab demonstrated superiority in achieving PASI 90 at week 16 (79.0% vs 57.6%, respectively; P<.0001) and PASI 75 at week 4 (44.3% vs 28.4%, respectively; P<.0001).
Side Effects
The most common side effects with secukinumab are increased risk of common mild infections, headache, eczema, pruritus, and diarrhea (Table 1). Infections are more common during the 12-week induction period than the maintenance period. The mechanism for increased common infections is not well-defined; it is possible that patients whose skin (and joint) disease has cleared spend more time in public and are simply exposed to more common infections.
There is an increased risk of Candida infections with IL-17 inhibition, which is dose dependent. All Candida infections in the secukinumab trials responded to standard treatment and did not necessitate drug discontinuation.
No systemic candidiasis infection, reactivation of latent tuberculosis (TB), or viral hepatitis were observed in any of the trials. While no cases of reactivated TB have been reported, screening for active and latent TB prior to starting secukinumab is recommended (Table 2).
Neutropenia is a rare side effect with secukinumab. The majority of cases of neutropenia were mild, transient, and reversible. Three cases of neutropenia were found in patients with nonserious infections including rhinitis, upper respiratory tract infections, and cystitis, though no cases resulted in drug discontinuation. As a precaution, a complete blood count should be performed if a patient on secukinumab presents with concerning symptoms or signs of infection.
Article continues on page 2
{{pagebreak}}
With other biologics such as adalimumab (Humira), the formation of antidrug antibodies (ADAs) could lead to a decrease in the efficacy of the drug. However, only 0.4% of patients in clinical trials developed ADAs to secukinumab. Furthermore, these antibodies did not lead to loss of efficacy or decreased drug concentration.
While a slight increase in serum transaminases was observed in patients on secukinumab, the majority of these cases were transient, resolving during the study. No cases of drug-induced liver injury were noted.
Secukinumab did not appear to increase the risk of solid tumors, lymphoma, leukemia, or skin cancer. Four patients developed malignant melanoma on secukinumab, but these individuals had several risk factors including prior exposure to phototherapy, tumor necrosis factor-alpha antagonist, or methotrexate use.
Hypersensitivity reactions can occur with secukinumab. Urticaria was the most common reaction. All cases of urticaria were nonserious and mild to moderate in severity.
Contraindications
Secukinumab should be used with caution in patients with Crohn’s disease. In prior studies, secukinumab was not effective at treating Crohn’s disease. In clinical trials for psoriasis, there were 3 patients who had flares of their Crohn’s disease out of over 3000 patients in those trials.
Live vaccines should not be given while on secukinumab (because there is no study showing they would be safe, not because they have been shown unsafe). If any live vaccines are needed, they should be given prior to initiating treatment with secukinumab. Nevertheless, a clinical study found no impact of secukinumab on antibody responses to killed influenza and meningococcal vaccinations.
Secukinumab is classified as pregnancy category B drug with no adverse effects on pregnancy in animal studies. There are no clinical trials of secukinumab in pregnant women. Secukinumab should only be used during pregnancy if the benefits outweigh the potential, unknown risks to the fetus. Because very little is known about the safety of secukinumab during pregnancy and nursing, caution should be exercised when prescribing secukinumab in these patients.
Monitoring
Due to the side effects of secukinumab, there are several recommended screening tests to perform in patients before and after they start secukinumab (Table 3). Because long-term data is not available for secukinumab, there are also several optional recommendations to prevent possible unknown long-term side effects.
Tips and Tricks
1. Ideal patients for secukinumab are those who have failed topical treatment, are interested in a biologic with the best chance at clearing their skin, and also are aware of the potential for possible, unforeseen long-term side effects due to lack of long-term studies.
2. Baseline TB test is recommended, however the mechanism of action of secukinumab is not expected to lead to an increased risk of tuberculosis.
3. Given the cost of this new drug, there are many opportunities available to help patients afford secukinumab. These options include a patient assistance foundation, a manufacturer’s coupon for free doses, and a $0 copay plan.
4. Deficiencies in the IL-17 pathway are associated with susceptibility to superficial Candida infections. Let patients know about the risk of yeast infection and that you can prescribe fluconazole if needed.
This article is an except from the book, Practical Psoriasis Management.
Dr. Culp is a fourth year medical student at Wake Forest School of Medicine.
Dr. Farhangian is a fourth year medical student at SUNY Downstate College of Medicine in Brooklyn, NY.
Dr. Feldman is with the Center for Dermatology Research and the Departments of Dermatology, Pathology and Public Health Sciences at Wake Forest University School of Medicine in Winston-Salem, NC.
Disclosure: The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, L.P. Dr. Feldman is a consultant and speaker for Galderma, Stiefel/GlaxoSmithKline, Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Genentech, BiogenIdec, and Bristol-Myers Squibb. Dr. Feldman has received grants from Galderma, Astellas, Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Genentech, BiogenIdec, Coria/Valeant, Pharmaderm, Ortho Pharmaceuticals, Aventis Pharmaceuticals, Roche Dermatology, 3M, Bristol-Myers Squibb, Stiefel/GlaxoSmithKline, Novartis, Medicis, Leo, HanAll Pharmaceuticals, Celgene, Basilea, and Anacor and has received stock options from Photomedex. He is owner of www.DrScore.com and a founder of Causa Research.
Disclosure: The authors report no relevant financial relationships.
Suggested References
1. Blauvelt A, Prinz JC, Gottlieb AB, et al. Secukinumab administration by pre-filled syringe: Efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol. 2015;172(2):484-493.
2. Gooderham M, Posso-De Los Rios CJ, Rubio-Gomez, GA, Papp K. Interleukin-17 (Il-17) inhibitors in the treatment of plaque psoriasis: A review. Skin Therapy Lett. 2015;20(1):1-5.
3. Yamauchi PS, Bagel J. Next-generation biologics in the management of plaque psoriasis: A literature review of IL-17 inhibition. J Drugs Dermatol. 2015;14(3):244-250.
4. Ohtsuki M, Morita A, Abe M, et al. Secukinumab efficacy and safety in Japanese patients with moderate-to-severe plaque psoriasis: Subanalysis from ERASURE, a randomized, placebo-controlled, phase 3 study. J Dermatol. 2014;41(12):1039-1046.
5. Paul C, Lacour JP, Kreutzer K, et al. Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol. 2015;29(6):1082-1090.
6. Sanford M, McKeage K. Secukinumab: first global approval. Drugs. 2015;75(3):329-338.
7. Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis-results of two phase 3 trials. N Engl J Med. 2014;371(4):326-338.
8. Colombel JF, Sendid B, Jouault T, Poulain D. Secukinumab failure in Crohn’s disease: the yeast connection? Gut. 2013;62(5):800-801.
