European S3‐Guideline on the systemic treatment of psoriasis vulgaris – Update Apremilast and Secukinumab – EDF in cooperation with EADV and IPC

• DOI: 10.1111/jdv.14454
• Publication Date: 2017-09-12T04:52:50Z
• Authors: A. Nast; P.I. Spuls; G. van der Kraaij; P. Gisondi; C. Paul; A.D. Ormerod; P. Saiag; C.H. Smith; E. Dauden; E.M. de Jong; E. Feist; R. Jobling; M. Maccarone; U. Mrowietz; K.A. Papp; K. Reich; S. Rosumeck; T. Talme; H.B. Thio; P. van de Kerkhof; R.N. Werner; C. Dressler
• Keywords: Ixekizumab; Apremilast; Venereology; Biosimilar

An update of the European S3-Guidelines on systemic treatment psoriasis vulgaris – Dermatology Forum (EDF) in cooperation with Academy and Venereology (EADV) International Psoriasis Council (IPC was published December 2015.1, 2 In addition to interventions discussed update, Committee for Medicinal Products Human Use (CHMP) Medicines Agency (EMA) approved apremilast secukinumab as new options psoriasis. The Commission granted a marketing authorization both treatments 15 January 2015.3, 4 February 2016, EMA also ixekizumab,5 which will be further expert group felt that at time consensus conference, experience ixekizumab still too limited allow conclusive discussion. methods used develop this amendment were accordance those previously vulgaris–Update Details fast can found report (https://doi.org/10.1111/jdv.14470). A systematic search identify relevant randomized controlled trials investigating and/or conducted Medline, Medline In-Process, Embase Cochrane Library 23.02.2016. Autoalerts screened until 27 July 2016. Briefly, studies assessing efficacy safety or patients moderate-to-severe included. literature screening performed collaboration (Stefanie Rosumeck, Corinna Dressler, Gayle van der Kraaij, Paula Lumig, Marlies Wakkee). Originally, 559 hits identified, 173 duplicates removed. Through autoalerts, 14 additional identified. After double inspection 400 title/abstracts, 16 full texts data extracted using standardized form, outcome analysed Review Manager.6 risk bias included assessed Risk Bias Assessment Tool.7 Evidence summarized according system recommended by GRADE (Grading Recommendations Assessment, Development Evaluation) working group.8 Drafts Dutch Guidelines9, 10 taken into consideration partly adapted. online conference held 02. November 2016 formal methodology nominal technique agree upon recommendations. These recommendations along their strengths are highlighted grey boxes throughout document. Standardized languages based GRADE: Pretreatment During Post-treatment No information is given summary products characteristics (SmPC)11 duration contraception after discontinuation apremilast. Continuation five half-lives (5 × 9 h) suggested. Strong dose 30 mg BID. initial titration schedule required shown above (Table 2). ‘The most commonly reported adverse reactions Phase III clinical have been gastrointestinal (GI) disorders including diarrhoea (15.7%) nausea (13.9%). GI mostly mild moderate severity, 0.3% being severe. generally occurred within first weeks usually resolved 3)’.11 Vomiting, dyspepsia, frequent bowel movements, upper abdominal pain gastroesophageal reflux disease, decreased appetite, respiratory infection, nasopharyngitis, bronchitis, cough, back pain, fatigue, insomnia, tension headache, migraine, depression ‘Patient weight measured routinely studies. mean observed loss treated up 52 1.99 kg. total 14.3% receiving had between 5% 10% while 5.7% >10%. None these overt consequences resulting from loss. 0.1% discontinued due reaction decreased’.11 underweight should monitored start treatment. case inexplicable significant loss, considered. See below special patient population 5) Neurological psychiatric disease. 2/3 more infections compared placebo.12-14 There no reactivations tuberculosis opportunistic reported.12-15 Screening latent not before enrolment trials; however, history incompletely an exclusion criterion.12-15 Surgery: Real-life perioperative management yet become available. However, there evidence date continuous lead complications. Patients who need minor surgical dental skin surgery may continue major surgery, decision withdrawal case-by-case considering characteristics, worsening counselling surgeon. Co-administration strong cytochrome P450 3A4 (CYP3A4) enzyme inducer, rifampicin, resulted reduction exposure apremilast, result apremilast.16 Therefore, use CYP3A4 inducers 4) recommended. clinically meaningful drug–drug interaction ketoconazole, methotrexate oral contraceptives.16 ‘In overdose, it any signs symptoms effects appropriate symptomatic instituted’.11 dosage adjustment necessary elderly patients.11 overall differences profile ≥65 years age younger adult <65 pharmacokinetic subjects over 75 trials. maximum concentration (Cmax) (65–85 age) about 6% higher than young (18–55 age).11 Five evaluating apremilast12-15, 17-19 evidence-based assessment. Summary findings tables available Supporting information. Apremilast effective placebo during induction therapy PASI 75/90 (low/moderate quality), percentage (low PGA ‘clear/almost clear’ quality) absolute DLQI (very low but ‘clear’ quality). Significantly experienced least one AE groups difference SAE response relapse rate (moderate Time till onset action faster long-term (moderate/low BID 20 all outcomes: (high marginally could superior lower 90 withdrew BID/20 QW QD BID/QD only etanercept TB monitoring (EMA/FDA approved) label. As June 117 728 exposed Among patients, three reports reported. Of tuberculosis, two insufficient last tuberculosis. It known when diagnosis made relation initiation continued (personal communication Celgene, email Ian Parson, 19 2016) pharmacokinetics its metabolite M12 affected severe hepatic impairment. This studied without psoriatic arthritis. impairment’.11 HIV-infected For general HIV see 2015 EU guidelines.1, If considered other alternatives, infectious disease specialist. serious neurological events complicated (demyelinating diseases TNF inhibitors progressive multifocal leucoencephalopathy efalizumab, fumaric acid esters) rare became evident some licensing. needs remembered context disorders. Headaches (tension), enough precipitate drug withdrawal, PDE4 inhibitors. Depression mentioned product (SmPC) potential side effect, placebo-controlled period phase 1.2% (14/1184) reporting 0.5% (2/418) placebo.11 ‘Postmarketing March 65 cases distributed follows: completed suicides, four suicide attempts, 50 suicidal ideation, behaviour. 32 65, available, improvement discontinuation. (From launch approximately 105 000 apremilast.)’20 affect cardiovascular risk. Congestive heart failure contraindication use. insulin resistance. Diabetes According label, mild-to-moderate renal impairment do require adjustment. reduced once daily (creatinine clearance <30 mL per minute)’11 (initial morning dose). pivotal trials, emergent related function.5, 6 contraindicated pregnancy. Pregnancy excluded initiated. pregnant women. breast-feeding. ‘No fertility humans. animal mice, males levels threefold females onefold exposure.’11 Adapted Ann Rheum Dis 2016;75:499-510, https://doi.org/10.1136/annrheumdis-2015-208337 League Against Rheumatism (EULAR) arthritis pharmacological therapies: update21 neither nor mentioning SMPC vaccination. live vaccinations permitted enrolled 300 subcutaneous injection dosing Weeks 0, 1, 3, followed monthly maintenance starting Week 4. Each injections 150 mg’.22 plaque psoriasis, 28.7% 18.9% placebo. Most infection tract did Mucosal cutaneous candidiasis secukinumab. Cases responded standard discontinuation.22 neutropenia transient reversible. Grade 3 dependency temporal relationship cases. Secukinumab specific antidrug antibodies detected Meso Scale Discovery bridging assay (sensitivity: ng/mL). 2842 participated six II studies, 11 (0.4%) developed whom neutralizing antibodies.23 effect Crohn's proof-of-concept trial.24 mg/kg administered i.v. day 1 22. study prematurely lack effect. Four 39 exacerbations trial program, pre-existing disease.25 caution exercised alternative biologicals Combinations immunosuppressive agents (except methotrexate)22 phototherapy studied. Il-17 has direct CYP450 expression. anti-inflammatory influence therefore might interact doses dependent medication, especially narrow therapeutic range such warfarin.22 Therapeutic drugs overdose Doses instituted immediately. ‘Based analysis number (n = 71 n 7 ≥75 years), similar’.22 Eight (SEC)26-32 presented important Onset rapid respect quality, important), statistically shorter w0,1,2,4 w0,4,8 concerning regard ustekinumab Expert opinion: increased immunosuppression Combination rheumatology22 IgGs mainly eliminated via catabolism expected secukinumab’.22 guidelines.1 specialist close infections. rare, currently indication associated diseases. produced non-significant brain lesions size multiple sclerosis.33 IL-17 does play prominent role chronic involved coronary artery show increase fraction diabetes mellitus. negative control. function.27, 28 ‘Women childbearing method adequate Animal indicate indirect harmful pregnancy, embryonic/foetal development, parturition postnatal development (see section 5.3). precautionary measure, preferable avoid pregnancy’.22 ‘It whether excreted human milk. Immunoglobulins milk if absorbed systemically ingestion. Because nursing infants secukinumab, discontinue breast-feeding must taking account benefit child woman’.22 evaluated. fertility’.22 2016;75:499-510 update.21 receive concurrent inactived non-live vaccinations. vaccination against influenza meningococci healthy humoural immune protection obtained.34 SmPC,22 vaccines under therapy.