New drug
Secukinumab for psoriasis
- First published 19 November 2015
- Aust Prescr 2016;39:64-6
- 1 April 2016
- DOI: 10.18773/austprescr.2016.011
ISSUE 2 APRIL
Approved indication: psoriasis
Cosentyx (Novartis)
prefilled syringe or pen containing 150 mg/mL for injection
Australian Medicines Handbook section 8.2
Psoriasis is known to be an immune-mediated inflammatory skin disease. While many patients can be managed with topical treatments, systemic therapy may be needed in patients with moderate or severe disease. Severe plaque psoriasis has been treated with tumour necrosis factor antagonists such as etanercept, and immunosuppressant drugs such as methotrexate, cyclosporin and ustekinumab.
Like ustekinumab, secukinumab is a monoclonal antibody produced by genetic engineering. It binds with the cytokine interleukin 17A. This prevents interleukin 17A from binding to its receptors thereby modifying immune and inflammatory responses.
Secukinumab has to be injected. As the recommended dose is 300 mg, two subcutaneous injections are required. It then takes approximately six days to reach the peak concentration. Monthly injections produce a steady state after 24 weeks of treatment. As secukinumab is an antibody, it is probably catabolised like other peptides. It has a half-life of 22–31 days.
A placebo-controlled trial (ERASURE) studied 150 mg and 300 mg doses of secukinumab injected weekly for five weeks then once every four weeks. Although the 737 patients were followed up for 52 weeks, the primary end points were assessed after 12 weeks. These end points were the investigators’ global assessments and a reduction in the Psoriasis Area and Severity Index (PASI). A reduction of at least 75% of the PASI score was achieved by significantly more of the patients taking secukinumab (see Table). A 100% reduction was achieved by 28.6% of the patients injecting 300 mg, 12.8% of those injecting 150 mg, but only 0.8% of the placebo group. These significant differences were reflected in the investigators’ global assessments.1
Table - Efficacy of secukinumab in plaque psoriasis 1
| Trial | Treatment (patients) | Proportion achieving primary end point ‡ | |
|---|---|---|---|
| ERASURE | secukinumab | 300 mg (245) | 81.6% |
| 150 mg (243) | 71.6% | ||
| placebo (246) | 4.5% | ||
| FIXTURE | secukinumab | 300 mg (323) | 77.1% |
| 150 mg (327) | 67.0% | ||
| etanercept | 50 mg (323) | 44.0% | |
| placebo (324) | 4.9% | ||
Another placebo-controlled trial (FIXTURE), involving 1306 patients, studied the same regimens, but included subcutaneous etanercept as an active control. These patients were also followed up for 52 weeks and efficacy was assessed at week 12. The response to secukinumab was significantly greater than the response to placebo and etanercept whether assessed by the PASI or the investigator (see Table). There was a 100% reduction in the PASI score in 24.1% of the secukinumab 300 mg group and 14.4% of the 150 mg group, compared with 4.3% of the etanercept group and none of the placebo group.1
In both trials response to therapy was sustained in most (72–84%) patients treated for up to 52 weeks. The statistically significant advantage over etanercept was also maintained.1
Two trials have studied the feasibility of patients injecting themselves using prefilled devices. A total of 359 patients were randomised. They injected themselves with secukinumab 150 mg or 300 mg, or a placebo weekly for five weeks and then monthly, with efficacy assessed at 12 weeks. In the trial of prefilled syringes, a reduction of 75% on the PASI score was achieved by 75.9% of patients injecting 300 mg, 69.5% of those injecting 150 mg and none of the placebo group.2 The corresponding responses in the trial of an autoinjector pen were 86.7%, 71.7% and 3.3%.3 All the patients were able to use the devices.
The main adverse effects reported in the trials were nasopharyngitis and other upper respiratory symptoms. Patients taking secukinumab were also more prone to develop diarrhoea than those taking placebo. Neutropenia developed in 1% of patients.1 As secukinumab affects the immune system, there is an increased risk of infections such as candidiasis and oral herpes. Patients should be tested for tuberculosis before treatment. Live vaccines should not be given. Patients can have hypersensitivity reactions to secukinumab, but only 1% of patients developed antibodies to the drug during a year of treatment. There are no studies of drug interactions and secukinumab has not been assessed in pregnant or breastfeeding women.
Secukinumab has been shown to be effective for the treatment of plaque psoriasis for at least 52 weeks. Longer term studies will report on the efficacy and safety of continued treatment. While secukinumab appears to have an advantage over etanercept, the full results of a comparison with ustekinumab in 676 patients were not published at the time of writing. Results at 16 weeks showed a 90% improvement in the PASI score for 79% of the secukinumab group and 57.6% of the ustekinumab group.4 Other drugs acting on interleukin 17A are also likely to emerge in the future.
🅃 🅃 manufacturer provided additional useful information
The Transparency Score is explained in New drugs: transparency, Vol 37 No 1, Aust Prescr 2014;37:27.
References
- Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K. Secukinumab in plaque psoriasis--results of two phase 3 trials. N Engl J Med 2014;371:326-38.
- Blauvelt A, Prinz JC, Gottlieb AB, Kingo K, Sofen H, Ruer-Mulard M. Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol 2015;172:484-93.
- Paul C, Lacour JP, Tedremets L, Kreutzer K, Jazayeri S, Adams S. Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol 2015;29:1082-90.
- Tha\u00e7i D, Blauvelt A, Reich K, Tsai TF, Vanaclocha F, Kingo K. 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;73:400-9.
Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
