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Management


maintained their PASI75 response.8 A multicentre, double-blind, open-


label, four-year extension to the SCULPTURE and STATURE studies was carried out. In SCULPTURE, 642 patients who completed 52 weeks of treatment continued into the extension. During the core study, PASI75 responders at week 12 were randomised to double-blind maintenance treatment of subcutaneous secukinumab 300mg or 150mg, administered either at a four- week fixed-interval (FI) regimen (320 patients) or in a retreatment-as-needed (RAN) regimen (322 patients). At entry into the extension, patients continued with the same blinded maintenance treatment regimen and dose that they had received in the SCULPTURE core study.9


.


In this extension study, 168 subjects received secukinumab 300mg in a fixed dosing schedule for three years; 69% achieved PASI90 at year one. This response was extremely well maintained after three years with 64% of patients continuing to have a PASI90 response. In addition, 43% of patients maintained completely clear skin (PASI100) at year three (from 44% at year one). A total of 83% achieved the standard treatment goal of PASI75 skin clearance at three years (from 89% at year one).9


Immunogenicity


Secukinumab demonstrated very low immunogenicity during long-term treatment in psoriasis subjects across six Phase III studies, and was not associated with PK abnormalities, hypersensitivity reactions, or loss of efficacy. It exhibited low levels of treatment-emergent anti-drug antibodies (TE-ADA) in subjects with moderate to severe psoriasis. Development of TE-ADA or neutralising antibodies did not affect the efficacy of secukinumab.10


A four-year extension of ERASURE and FIXTURE evaluated the immunogenicity of secukinumab at 104 weeks of treatment. TE-ADA and neutralising antibodies were reported rarely with secukinumab treatment out to two years, and were not associated with loss of secukinumab efficacy or other issues of clinical concern.11


Quality of life


The drug has a positive effect on health-related quality of life.2


The


number of patients at week 12 with a DLQI score of 0 or 1 were significantly


(p<0.001) higher with secukinumab 300mg than with placebo in ERASURE (58.8% versus 10.3%), and etanercept and placebo in FIXTURE (56.7 versus 34.5% and 6.6%, respectively).2 Moreover, the percentage of patients at week 16 with a DLQI score of 0 or 1 in the CLEAR study was significantly higher with secukinumab than with ustekinumab (71.9 versus 57.4%; p<0.0001).5


Tolerability


Secukinumab is generally well tolerated in mild to moderate plaque psoriasis.12 Pooled safety data from the clinical development program, including ten Phase II/III studies with 2725 subject years of secukinumab exposure, showed incidence rates of overall adverse events and and adverse events of special interest in the secukinumab groups were comparable to those in the etanercept and placebo groups, with no apparent difference between the two secukinumab doses.12


The most common adverse events with secukinumab were: nasopharyngitis; headache; upper respiratory tract infections; arthralgia; hypertension; diarrhoea; back pain; and cough.12


Psoriatic arthritis


A sub-analyses of ERASURE and FIXTURE demonstrated that


secukinumab 300mg produced significant improvement in psoriasis and physical functioning in subjects with plaque psoriasis and concomitant psoriatic arthritis (PsA).13


of IL-17A blockade for the treatment of PsA is being explored in ongoing double-blind, randomised, placebo- controlled Phase III trials.


Conclusions


Secukinumab was more effective than placebo, etanercept and ustekinumab at improving both psoriasis symptoms (with high skin clearance) and health-related quality of life. Moreover, secukinumab was more effective than placebo in studies specifically investigating efficacy in the difficult-to-treat palmoplantar and nail psoriasis populations. Secukinumab is generally well tolerated, with low immunogenicity. Efficacy is sustained in the longer-term. Secukinumab is an effective first-line systemic treatment for moderate to severe plaque psoriasis, and is a useful addition to the treatment armamentarium for this condition. ●


References 1. Novartis Europharm Ltd. Summary of Product Characteristics 2015. Cosentyx (secukinumab subcutaneous injection).


2. Langley R et al. Secukinumab in plaque psoriasis – results of two phase 3 trials. N Engl J Med 2014;371:326–38.


3. Blauvelt A et al. Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol 2014;172(2):484–93.


4. Paul C et al. Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol 2014;29(6):1082–90.


5. Thaci D et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial. J Am Acad Dermatol 2015;73(3):400–9.


6. Gottlieb A et al. Secukinumab efficacy and safety in subjects with moderate to severe palmoplantarpsoriasis in a phase 3b study (GESTURE) [abstract no. FC24-07]. In: 23rd World Congress of Dermatology, 2015.


7. Reich K et al. Secukinumab is effective in subjects with nail psoriasis: 16 week results from the TRANSFIGURE study [abstract]. In: 23rd World Congress of Dermatology, 2015.


8. Blauvelt A et al. Secukinumab treatment maintains efficacy in moderate to severe plaque psoriasis through second year of treatment: A randomized extension of the ERASURE and FIXTURE studies. Presented at the American Academy of Dermatology 2015;Abstract F010.8.


The therapeutic potential


9. Bissonnette R et al. Secukinumab maintains high levels of efficacy through 3 years of treatments: results from an extension to a phase 3 study (SCULPTURE). Presented at the European Academy of Dermatology and Venereology 2015.


10. Reich K et al. Secukinumab, a novel anti IL-17A, exhibits low immunogenicity during long-term treatment in subjects with psoriasis. Psoriasis From Gene to Clinic 7th International Congress;11-13 December 2014:P103.


11. Reich K et al. Secukinumab exhibits low immunogenicity during 104 weeks of treatment in subjects with moderate to severe plaque psoriasis. Presented at the European Academy of Dermatology and Venereology 2015.


12. Griffiths C et al. Secukinumab demonstrates an acceptable safety profile in moderate to severe plaque psoriasis: Pooled analysis of 10 phase 2/3 studies. Presented at 4th World Psoriasis and Psoriatic Arthritis Conference; 8–11 July 2015:P051.


13. Gottlieb A et al. Secukinumab improves physical function in subjects with plaque psoriasis and psoriatic arthritis: Results from two randomized, phase 3 trials. J Drugs Dermatol 2015;14(8): 821–33.


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