Nast 2017
Nast 2017
Nast 2017
14454 JEADV
GUIDELINES
Conflicts of interest
All authors declared their potential conflicts of interest. A detailed list is available in the methods report DOI:
https://doi.org/10.1111/jdv.14470.
Funding sources
The guideline project has kindly been supported by the European Dermatology Forum EDF. The financial support
did not influence the guideline development and context.
2 weak recommendation for the intervention (‘We suggest. . .’ ALT, AST x (x)
Serum creatinine/eGFR x (x)
↑),
Pregnancy test (urine) x (x)
3 no recommendation (‘We cannot make a recommendation
Hepatitis B and C† Optional (x)
with respect to. . ..’ ○),
HIV Optional (x)
4 weak recommendation against (‘We suggest against. . .’ ↓)
Not all tests may be necessary for all patients. Medical history, risk exposure
and
and patient characteristics have to be taken into account. Further specific
5 strong recommendation against (‘We recommend against. . .’ testing may be required according to clinical signs, risks and exposure.
↓↓). *Hb, Hct, leucocytes, platelets.
†see ‘Hepatitis/other hepatological dysfunctions’.
Strong consensus
Dosing The recommended dose is 30 mg BID. An initial titra- infections reported.12–15 Screening for latent tuberculosis was
tion schedule is required as shown above (Table 2). not required before enrolment in the randomized clinical trials;
however, a history of incompletely treated tuberculosis was an
Adverse drug reactions/safety
exclusion criterion.12–15
Table 3 Overview of important side effects, adapted from Ref11 Special considerations during treatment
Very frequent Nausea, diarrhoea, weight loss
Surgery: Real-life data on perioperative management of apremi-
last have not yet become available. However, there is no evidence
Frequent Vomiting, dyspepsia, frequent bowel movements,
upper abdominal pain to date that continuous treatment with apremilast will lead to
gastroesophageal reflux disease, decreased appetite, perioperative complications. Patients who need minor surgical
upper respiratory infection, nasopharyngitis, treatments including dental treatments and skin surgery may
bronchitis, cough, back pain, fatigue, insomnia,
continue apremilast treatment. In the case of major surgery, the
tension headache, migraine, depression
decision of apremilast withdrawal should be taken case-by-case
Occasional Hypersensitivity, rash
considering patient characteristics, the risk of infection, the risk
Rare –
of psoriasis worsening and after counselling with the surgeon.
Very rare –
Table 4 List of most important drugs with potential interactions included outcomes: PASI 75/90 (moderate quality), percentage
Drugs with strong cytochrome P450 3A4 (CYP3A4) enzyme inducing PASI reduction (moderate quality), PGA ‘clear/almost clear’
effect (moderate quality), PGA ‘clear’ (moderate quality), absolute
Rifampicin reduction in DLQI (high quality), patients with at least one AE
Phenobarbital (high quality), patients with at least one SAE (low quality) and
Carbamazepine withdrawal due to AE (moderate quality).
Phenytoin Time until onset of action was marginally faster in apremilast
St. John’s Wort 30 mg BID than apremilast 20 mg BID (low quality).
No differences could be found for apremilast 30 mg BID com-
Overdose/measures in case of overdose pared to apremilast 20 mg BID for long-term therapy for all
‘In case of an overdose, it is recommended that the patient is included outcomes: PASI 75/90 (moderate quality), PGA ‘clear/al-
monitored for any signs or symptoms of adverse effects and most clear’ (moderate quality), PGA ‘clear’ (moderate quality),
appropriate symptomatic treatment is instituted’.11 absolute reduction in DLQI (high quality), patients with at least one
AE (moderate quality) and withdrawal due to AE (high quality).
Special considerations
Apremilast 30 mg BID compared to apremilast 10 mg
Elderly patients No dosage adjustment is necessary for elderly
BID Apremilast 30 mg BID is superior to apremilast 10 mg
patients.11 No overall differences were observed in the safety BID in the induction therapy based on PASI 75 (high quality),
profile of elderly patients ≥65 years of age and younger adult percentage PASI reduction (moderate quality) and PGA ‘clear/
patients <65 years of age in the clinical studies. There is limited almost clear’ (high quality). The higher dose was not superior to
pharmacokinetic data in subjects over 75 years of age in clinical the lower dose based on PASI 90 (moderate quality), PGA ‘clear’
trials. The maximum concentration (Cmax) for apremilast in (low quality) and absolute reduction in DLQI (high quality).
elderly subjects (65–85 years of age) is about 6% higher than Significantly more patients experienced at least one AE (mod-
that in young subjects (18–55 years of age).11 erate quality) or withdrew due to an AE (high quality) in the
higher dose groups but no differences could be found for
Quality of evidence – apremilast
patients with at least one SAE (low quality).
Time until onset of action was faster in apremilast 30 mg BID
Five studies evaluating apremilast12–15,17–19 were included in the
than apremilast 10 mg BID/20 mg QW (low quality).
evidence-based assessment. Summary of findings tables is available
Apremilast 30 mg BID is superior to apremilast 10 mg BID in
as Supporting information.
long-term treatment based on PASI 75/90 (high quality) and
Apremilast compared to placebo12–15,17–19 PGA ‘clear/almost clear’ (high quality). The higher dose was not
Apremilast was found to be more effective than placebo during superior to the lower dose based on PGA ‘clear’ (moderate qual-
induction therapy based on PASI 75/90 (low/moderate quality), ity) and absolute reduction in DLQI (high quality). No differ-
percentage reduction in PASI (low quality), PGA ‘clear/almost clear’ ences could be found for patients with at least one AE (moderate
(low quality) and for absolute DLQI reduction (very low quality) quality) or withdrawal due to AE (low quality).
but not based on PGA ‘clear’ (low quality). Significantly more
patients experienced at least one AE in the apremilast groups com- Apremilast 20 mg BID compared to apremilast 10 mg BID/
pared to placebo (low quality). No difference was found for patients 20 mg QD Apremilast 20 mg BID is superior to apremilast
with at least one SAE (low quality) and for withdrawal due to AE 10 mg BID/20 mg QD in the induction therapy based on PASI 75
(low quality). After response to apremilast, there was no difference (high quality), percentage PASI reduction (moderate quality) and
in relapse rate after 16 weeks of treatment (moderate quality). PGA ‘clear/almost clear’ (moderate quality) and absolute reduction
Time till onset of action was faster for apremilast than placebo in DLQI (moderate quality). The higher dose was not superior
(very low quality). based on PASI 90 (moderate quality) or PGA ‘clear’ (low quality).
Apremilast was also found to be more effective than placebo in No differences could be found for patients with at least one
long-term therapy based on PASI 75/90 (moderate/low quality) and AE (low quality), patients with at least one SAE (moderate qual-
PGA ‘clear/almost clear’ (low quality). No safety data were available. ity) or withdrawal due to AE (very low quality). After response
to apremilast, there was no difference in relapse rate within
Apremilast in different dosages12,15 16 weeks of treatment (moderate quality).
Time until onset of action was faster for apremilast 20 mg
Apremilast 30 mg BID compared to apremilast 20 mg BID No BID than apremilast 10 mg BID/20 mg QW (low quality).
differences were found between apremilast 30 mg BID and No differences could be found between apremilast 20 mg BID
apremilast 20 mg BID for induction therapy based on all and apremilast 10 mg BID/QD in long-term treatment based on
‘The pharmacokinetics of apremilast and its major metabolite multifocal leucoencephalopathy with efalizumab, fumaric acid
M12 are not affected by moderate or severe hepatic impairment. esters) are rare and became evident some years after licensing.
This was studied in patients without psoriasis or psoriatic arthri- This needs to be remembered when considering the safety profile
tis. No dose adjustment is necessary for patients with hepatic of apremilast and secukinumab in the context of neurological
impairment’.11 disorders.
Headaches (tension), which can be serious enough to precipi-
HIV There are no available data on HIV-infected patients tate drug withdrawal, are frequent and reported with other
treated with apremilast. For general recommendations on PDE4 inhibitors.
treatment of psoriasis in patients with HIV see 2015 update of Depression is mentioned in the summary of product charac-
EU Psoriasis guidelines.1,2 If treatment with apremilast is to be teristics (SmPC) as a potential side effect, based on findings dur-
considered in patients with no other alternatives, the decision ing the placebo-controlled period of phase III clinical trials with
should be taken in collaboration with the infectious disease 1.2% (14/1184) of patients treated with apremilast reporting
specialist. depression compared to 0.5% (2/418) with placebo.11
‘Postmarketing data up to 20 March 2016 reported 65 cases
Malignancies including lymphoma and skin cancer Patients distributed as follows: five completed suicides, four suicide
with malignancy or history of malignancy were excluded from attempts, 50 cases of suicidal ideation, five cases of depression
randomized controlled trials with apremilast, except for treated suicidal and one case of suicidal behaviour. In 32 cases of 65, for
basal cell or squamous cell carcinomas and cervical intraepithe- which information was available, the patients reported improve-
lial neoplasia [CIN] without evidence of recurrence within the ment after treatment discontinuation. (From launch to 20
previous 5 years. No report on the use of apremilast in patients March 2016, there were approximately 105 000 patients exposed
with malignancies has been reported to date. Therefore, as expert to apremilast.)’20
opinion we consider malignancies or lymphoproliferative disor- A number of anti-epileptic agents (e.g. carbamazepine,
ders as relative contraindications. phenytoin) are strong CYP3A4 enzyme inducers and may
reduce systemic exposure to apremilast when co-adminis-
tered.11
Congestive heart failure is not a contraindication to apremilast Vaccination There is neither published information nor
use. mentioning in the SMPC about the use of apremilast in the
context of vaccination. However, live vaccinations were per-
Diabetes mellitus There is no evidence that apremilast could mitted in patients enrolled in the randomized controlled
affect insulin resistance. Diabetes is not a contraindication for clinical trials.
apremilast use.
Secukinumab
Kidney failure/Renal impairment According to the label,
patients with mild-to-moderate renal impairment do not require Instructions for use
dose adjustment.
‘The dose of apremilast should be reduced to 30 mg once Pretreatment
daily in patients with severe renal impairment (creatinine clear- • Physicians are encouraged to enrol their patients in a
ance of <30 mL per minute)’11 (initial dose titration using only registry (if available)
the morning dose). • Objective assessment of the disease (such as PASI/BSA/
In the pivotal clinical trials, there was no evidence for treat- PGA; arthritis)
ment emergent adverse events related to renal function.5,6 • HRQoL (such as DLQI/Skindex-29 or -17)
• Medical history and physical examination including
Wish for pregnancy in near future Pregnancy. Apremilast is prior exposure to treatments, malignancies, infection
contraindicated during pregnancy. Pregnancy should be (TBC), Crohn’s disease and comedication (e.g. warfarin).
excluded before treatment can be initiated. There are limited
data about the use of apremilast in pregnant women. o Check for hypersensitivity
Breast-feeding. Apremilast should not be used during breast- o Check for skin cancer
feeding. o Check for evidence of active and chronic infection
o Check for contraception and breastfeeding
Fertility. ‘No fertility data is available in humans. In animal o Check need for vaccines
studies in mice, no adverse effects on fertility were observed in o Exclusion of tuberculosis (see chapter 5.1 in long
males at exposure levels threefold clinical exposure and in version of the Psoriasis Guidelines 20151)
females at exposure levels onefold clinical exposure.’11 • Laboratory controls including pregnancy test (see
Table 5)
During treatment
Psoriatic arthritis
• Objective assessment of the disease (such as PASI/BSA/
PGA; arthritis)
• HRQoL (such as DLQI/Skindex-29 or -17)
Recommendation Strength of Comment
consensus • Medical history and physical examination focusing on
malignancies, infections, contraception
Apremilast is suggested ↑ Strong Expert
for patients with psoriatic consensus opinion • Check for the possibility of tuberculosis infection. This
arthritis and an includes taking medical history and might include
inadequate response tuberculosis testing (see chapter 5.1 in long version of
to at least one
the Psoriasis Guidelines 20151).
csDMARD*, in whom
TNF inhibitors are • Laboratory controls see Table 5.
not appropriate. • Contraception
*csDMARD: conventional synthetic disease-modifying antirheumatic Post-treatment
drugs • Contraception should be pursued 20 weeks after dis-
continuation of secukinumab
Table 5 Recommended laboratory controls (sensitivity: 4 ng/mL). Among 2842 patients who participated in
Parameter Pretreatment Every 2–5 six phase II clinical studies, a total of 11 patients (0.4%) devel-
months oped antidrug antibodies of whom three developed neutralizing
Blood count* X X antidrug antibodies.23
CRP X X
Liver enzymes† X (X) Crohn’s disease The effect of secukinumab on Crohn’s dis-
Serum creatinine X (X) ease was studied in a randomized placebo-controlled proof-
Pregnancy test (urine) X (X) of-concept trial.24 Secukinumab 2 9 10 mg/kg was adminis-
Urine status X (X) tered i.v. on day 1 and day 22. The study was prematurely
Hepatitis B and C X (X)
discontinued due to lack of effect. Four of 39 patients
HIV X (X)
reported exacerbations of Crohn’s disease. In the phase III
TBC Testing‡ X (remain alert)
psoriasis clinical trial program, three cases of Crohn’s dis-
CRP, C-reactive protein; Not all tests may be necessary for all patients. Med-
ease were reported as serious adverse events of which two
ical history, risk exposure and patient characteristics have to be taken into
account. Further specific testing may be required according to clinical signs, were exacerbations of pre-existing disease.25 In patients with
risk and exposure. psoriasis and Crohn’s disease, caution should be exercised
*Hb, Hct, leucocytes, platelets, differential blood count. and alternative biologicals may be considered before using
†AST, ALT, AP, cGT.
secukinumab.
‡see chapter 5.1 in long version of the Psoriasis Guidelines 2015.1
Consensus
Special considerations during treatment
Surgery: Real-life data on perioperative management of secuk-
Dosing ‘The recommended dose is 300 mg of secukinumab by inumab have not yet become available. However, there is no evi-
subcutaneous injection with initial dosing at Weeks 0, 1, 2 and dence to date that continuous treatment with secukinumab will
3, followed by monthly maintenance dosing starting at Week 4. lead to perioperative complications. Patients who need minor
Each 300 mg dose is given as two subcutaneous injections of surgical treatments including dental treatments and skin surgery
150 mg’.22 may continue secukinumab treatment. In the case of major sur-
gery, the decision of secukinumab withdrawal should be taken
Adverse drug reactions/safety case-by-case considering patient characteristics, the risk of infec-
tion, the risk of psoriasis worsening and after counselling with
Table 6 Overview of important side effects, adapted from Ref23 the surgeon.
Very frequent Upper respiratory infections (nasopharyngitis, rhinitis)
Frequent Oral herpes, rhinorrhea, diarrhoea, urticaria Important contraindications/restrictions on use
Occasional Oral candidiasis, neutropenia, tinea pedis, otitis externa,
conjunctivitis Absolute contraindications
• Severe acute infection (e.g. active tuberculosis)
• Hypersensitivity to the active substance or to any of the
Infections In the placebo-controlled period of clinical stud- excipients
ies in plaque psoriasis, infections were reported in 28.7% of • Pregnancy or breastfeeding
patients treated with secukinumab and 18.9% of patients • Needs for/concomitant administration with live attenuated
with placebo. Most cases of infection were mild or moderate vaccine
upper respiratory tract infections which did not require
treatment discontinuation. Mucosal or cutaneous candidiasis Relative contraindications
was more frequent with secukinumab. Cases responded to • Acute and chronic infections (previous, latent or active
standard treatment and did not require treatment discontin- TBC, hepatitis B or C, HIV)
uation.22 • Malignancies or lymphoproliferative disorders
• Caution should be exercised when considering the use of
Neutropenia Most cases of neutropenia were mild transient secukinumab in patients with Crohn’s disease due to poten-
and reversible. Grade 3 neutropenia was observed in 0.5% of tial risk of exacerbation
patients with no dose dependency or temporal relationship to
infection in most cases. Drug interactions
Combinations of secukinumab with other immunosuppressive
Immunogenicity Secukinumab specific antidrug antibodies agents (except for methotrexate)22 or phototherapy have not
were detected by a Meso Scale Discovery bridging assay been studied.
Il-17 has no direct effect on CYP450 expression. The PASI 75 (high quality, but not clinically important), PASI 90
anti-inflammatory effect of secukinumab may influence (high quality), PGA ‘clear’ and ‘clear/almost clear’ (moderate
CYP450 levels and therefore might interact with the doses quality). No statistically significant difference was found for
of CYP450 dependent medication, especially those with a patients with at least one AE (high quality), patients with at
narrow therapeutic range such as warfarin.22 Therapeutic least one SAE (moderate quality) and withdrawal due to AE
monitoring of such drugs should be considered while start- (moderate quality).
ing secukinumab. Time till onset of action was shorter for 300 mg compared to
150 mg secukinumab (low quality).
Overdose/measures in case of overdose Secukinumab 300 mg is superior to secukinumab 150 mg
No cases of overdose have been reported. Doses of up to 30 mg/ in long-term therapy based on PASI 75 (high quality, but
kg have been administered in clinical studies. In case of over- not clinically important), PASI 90 (moderate quality), PGA
dose, the patient should be monitored and appropriate symp- ‘clear’ (moderate quality) and PGA ‘clear/almost clear’ (high
tomatic treatment be instituted immediately. quality).
Elderly patients ‘Based on population pharmacokinetic Secukinumab 150 mg w0,1,2,4 compared to Secukinmab
analysis with a limited number of elderly patients (n = 71 150 mg w0,4,831 Secukinumab 150 mg w0,1,2,4 was found to
for age ≥65 years and n = 7 for age ≥75 years), clearance be more effective than secukinumab 150 mg w0,4,8 in the
in elderly patients and patients <65 years of age was simi- induction therapy based on PASI 75/90 (moderate quality) and
lar’.22 PGA ‘clear/almost clear’ (moderate quality). No difference was
found concerning patients with at least one AE (high quality),
Quality of evidence – secukinumab patients with at least one SAE (moderate quality) and with-
drawal due to AE (low quality).
Eight studies evaluating secukinumab (SEC)26–32 were included
in the evidence-based assessment. The summary of findings Secukinumab (150 mg or 300 mg) compared to etanercept
tables are presented as Supporting information. (50 mg BIW)27
Secukinumab was superior to etanercept in the induction phase
Secukinumab (150 mg or 300 mg) compared to based on PASI 75/90 (high quality), PGA ‘clear/almost clear’
placebo26,27,29–31 (high quality) and PGA ‘clear’ (high quality). No difference was
Secukinumab was found to be more effective than placebo in the found concerning patients with at least one AE (high quality),
induction therapy based on PASI 75/90 (high quality) and PGA patients with at least one SAE (high quality) and withdrawal due
‘clear’ and ‘clear/almost clear’ (high quality). to AE (high quality).
Significantly more patients with at least one AE were Onset of action was more rapid for 300 mg and
reported in the secukinumab groups than in the placebo 150 mg secukinumab when compared to etanercept (low
groups (high quality), but not clinically important and no quality).
difference was found for patients with at least one SAE Secukinumab was superior to etanercept in long-term therapy
(moderate quality) and for withdrawal due to AE (moder- based on PASI 75/90 (moderate quality), PGA ‘clear/almost
ate quality). clear’ (low quality) and PGA ‘clear’ (moderate quality). No dif-
Onset of action was more rapid for 150 mg and 300 mg ference was found in regard to withdrawal due to AE (low qual-
secukinumab compared to placebo (low quality). ity).
Secukinumab was also found to be more effective than pla-
cebo in long-term therapy based on PASI 75/90 (high quality) Secukinumab (300 mg) compared to ustekinumab (45 mg/
and PGA ‘clear/almost clear’ (high quality). No data on adverse 90 mg)32
events were available. Secukinumab was superior to ustekinumab in the induction
phase based on PASI 75 (high quality, but not clinically impor-
Secukinumab in different dosages tant), PASI 90 (moderate quality), PGA ‘clear/almost clear’
(moderate quality) and PGA ‘clear’ (high quality). No difference
Secukinumab 300 mg compared to 150 mg26–30 Secuk- was found concerning patients with at least one AE (high
inumab 300 mg is superior to secukinumab 150 mg during quality), patients with at least one SAE (moderate quality) and
the induction treatment with respect to efficacy based on withdrawal due to AE (low quality).
Time till onset of action was shorter for secukinumab 300 mg Special patient populations
compared to ustekinumab (low quality).
Tuberculosis (TB) screening before and during secukinumab
treatment
Therapeutic recommendations
‘No pharmacokinetic data are available in patients with hep- Neurological disease The two serious neurological events
atic impairment. IgGs are mainly eliminated via catabolism and that have complicated therapy for psoriasis to date (demyeli-
hepatic impairment is not expected to influence clearance of nating diseases with TNF inhibitors and progressive multifo-
secukinumab’.22 cal leucoencephalopathy with efalizumab, fumaric acid esters)
are rare, and became evident some years after licensing. This
HIV There are no available data on HIV-infected patients trea- needs to be remembered when considering the safety profile
ted with secukinumab. of apremilast and secukinumab in the context of neurologi-
For general recommendations on treatment of psoriasis in cal disorders.
patients with HIV see 2015 update of EU Psoriasis guide- There is currently no indication that secukinumab is associ-
lines.1 ated with specific adverse events in patients with neurological
If treatment with secukinumab is to be considered in patients diseases.
with no other alternatives, the decision should be taken in col- Secukinumab produced a non-significant reduction in
laboration with the infectious disease specialist with close moni- brain lesions size in a proof-of-concept study in multiple
toring for infections. sclerosis.33
Malignancies including lymphoma and skin cancer No report Ischaemic heart disease and congestive heart failure IL-17
on the use of the drug in patients with a history of cancer has does not play a prominent role in chronic heart failure
been published to date. Although no increase of the risk of can- but may be involved in coronary artery disease. The stud-
cer has been reported in phase III trials with secukinumab as ies did not show an increase risk of major cardiovascular
compared to placebo or active comparators, no conclusion can events in patients treated with secukinumab compared to
be drawn due to lack of long-term safety data for patients with a placebo.
history of malignancies. No evidence-based recommendation
can be given for this population. Ongoing postmarketing reg- Diabetes mellitus A significant fraction of patients enrolled
istries in real life will give further information on the risk of can- in the clinical trials had diabetes mellitus. There is no evi-
cer during or after secukinumab treatment. Before the release of dence that secukinumab has any negative effect on diabetes
these results, clinicians should use this drug with caution in control.
patients with active or recent cancer.
Kidney failure/Renal impairment In the pivotal clinical trials,
there was no evidence for treatment emergent adverse events
related to renal function.27,28
For general recommendations on the treatment of psoriasis in patients
with current or previous malignancy see:
Update 2015 – European S3-Guidelines on the systemic treatment of Wish for pregnancy in near future Pregnancy. ‘Women of
psoriasis vulgaris1,2 childbearing potential should use an effective method of con-
Recommendation Strength of Comment traception during treatment and for at least 20 weeks after
consensus treatment. There are no adequate data from the use of
We recommend to discuss ↑↑ Strong Expert secukinumab in pregnant women. Animal studies do not
the decision to initiate consensus opinion
indicate direct or indirect harmful effects with respect to
secukinumab in psoriasis
patients with a current or
pregnancy, embryonic/foetal development, parturition or
recent diagnosis of cancer postnatal development (see section 5.3). As a precautionary
in the previous 5 years case measure, it is preferable to avoid the use of secukinumab in
by case with cancer specialists
pregnancy’.22
and to reach an informed
decision, respecting the Breast-feeding. ‘It is not known whether secukinumab is
patient’s preference.
excreted in human milk. Immunoglobulins are excreted in
The elements to be taken into Statement Strong Expert
human milk and it is not known if secukinumab is absorbed
account among other aspects consensus opinion
for the shared decision are the systemically after ingestion. Because of the potential for
type and staging of cancer, the adverse reactions in nursing infants from secukinumab, a deci-
risk of recurrence and the sion on whether to discontinue breast-feeding during treat-
burden of psoriasis in the
ment and up to 20 weeks after treatment or to discontinue
individual patient.
therapy with secukinumab must be made taking into account
the benefit of breast-feeding to the child and the benefit of 8 Guyatt GH, Oxman AD, Vist GE et al. GRADE: an emerging consensus
secukinumab therapy to the woman’.22 on rating quality of evidence and strength of recommendations. BMJ
2008; 336: 924–926.
9 Spuls PI, van den Boogaart L, de Groot M et al. Richtlijn Psoriasis 2011.
Fertility. ‘The effect of secukinumab on human fertility has not Nederlandse Vereniging voor Dermatologie en Venereologie (NVDV),
been evaluated. Animal studies do not indicate direct or indirect 2011.
10 Zweegers J, de Jong EM, Nijsten TE et al. Summary of the Dutch S3-
harmful effects with respect to fertility’.22
guidelines on the treatment of psoriasis 2011. Dutch Society of Dermatol-
ogy and Venereology. Dermatol Online J 2014; 20. pii: doj_21769.
Psoriatic arthritis 11 European Medicines Agency. Otezla - Summary of product characteristics
(Annex I). 08/07/2016 Otezla -EMEA/H/C/003746 -PSUSA/10338/
201506, 2016.
12 Papp K, Cather JC, Rosoph L et al. Efficacy of apremilast in the treatment
Recommendation Strength of Comment of moderate to severe psoriasis: a randomised controlled trial. Lancet
consensus 2012; 380: 738–746.
Secukinumab is ↑↑ Strong Expert 13 Papp K, Reich K, Leonardi CL et al. Apremilast, an oral phosphodi-
recommended for consensus opinion esterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque
patients with psoriatic psoriasis: results of a phase III, randomized, controlled trial (Efficacy and
arthritis and an Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM]
inadequate response 1). J Am Acad Dermatol 2015; 73: 37–49.
to at least one csDMARD, 14 Paul C, Cather J, Gooderham M et al. Efficacy and safety of apremilast,
in whom TNF inhibitors an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-
are not appropriate. severe plaque psoriasis over 52 weeks: a phase III, randomized controlled
trial (ESTEEM 2). Br J Dermatol 2015; 173: 1387–1399.
*csDMARD: conventional synthetic disease-modifying antirheumatic drug 15 Papp KA, Kaufmann R, Thaci D, Hu C, Sutherland D, Rohane P. Efficacy
and safety of apremilast in subjects with moderate to severe plaque psori-
asis: results from a phase II, multicenter, randomized, double-blind, pla-
Adapted from Ann Rheum Dis 2016;75:499-510 https://doi. cebo-controlled, parallel-group, dose-comparison study. J Eur Acad
org/10.1136/annrheumdis-2015-208337 European League Dermatol Venereol 2013; 27: e376–e383.
Against Rheumatism (EULAR) recommendations for the man- 16 Liu Y, Zhou S, Wan Y, Wu A, Palmisano M. The impact of co-adminis-
tration of ketoconazole and rifampicin on the pharmacokinetics of
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2015 update.21 1050–1057.
17 Green L, Thaci D, Zhang Z, Goncalves J, Nograles K, Nikkels A. Effect of
apremilast and etanercept on pruritus and health-related quality of life in
Vaccination Patients treated with secukinumab may receive
patients with moderate to severe plaque psoriasis: Results from the LIB-
concurrent inactived or non-live vaccinations. There is ERATE study. J Am Acad Dermatol 2016; 1: AB245.
published evidence that after vaccination against influenza 18 Reich K, Papp K, van de Kerkhof P, Zhang Z, Nograles K, Soung J. 52-
or meningococci in healthy subjects during treatment with Week efficacy in patients with moderate to severe psoriasis continued on
apremilast or switched from etanercept: the LIBERATE study. Australas J
secukinumab, adequate humoural immune protection is
Dermatol 2016; 57: 69–70.
obtained.34 19 Reich K, Soung J, Gooderham M, Zhang Z, Nograles K, Goodfield M.
According to the SmPC,22 live vaccines should not be given Sustained efficacy of apremilast in patients with moderate to severe psori-
under secukinumab therapy. asis who continued on apremilast or switched from etanercept treatment:
52-week results from the LIBERATE study. J Am Acad Dermatol 2016; 74:
AB276.
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