ObjectivesMAXIMISE (Managing AXIal Manifestations in psorIatic arthritis with SEcukinumab) trial was designed to evaluate the efficacy of secukinumab in the management of axial manifestations of psoriatic arthritis (PsA).MethodsThis phase 3b, double-blind, placebo-controlled, multi-centre 52-week trial included patients (≥18 years) diagnosed with PsA and classified by ClASsification criteria for Psoriatic Arthritis (CASPAR) criteria, with spinal pain Visual Analogue Score ≥40/100 and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4 despite use of at least two non-steroidal anti-inflammatory drugs (NSAIDs). Patients were randomised (1:1:1) to secukinumab 300 mg, secukinumab 150 mg or placebo weekly for 4 weeks and every 4 weeks thereafter. At week 12, placebo patients were re-randomised to secukinumab 300/150 mg. Primary endpoint was ASAS20 (Assessment of SpondyloArthritis international Society) response with secukinumab 300 mg at week 12.ResultsPatients were randomly assigned; 167 to secukinumab 300 mg, 165 to secukinumab 150 mg and 166 to placebo. Secukinumab 300 mg and 150 mg significantly improved ASAS20 response versus placebo at week 12 (63% and 66% vs 31% placebo). The OR (95% CI) comparing secukinumab 300 mg and 150 mg versus placebo, using a logistic regression model after multiple imputation, was 3.8 (2.4 and 6.1) and 4.4 (2.7 and 7.0; p<0.0001).ConclusionsSecukinumab 300 mg and 150 mg provided significant improvement in signs and symptoms of axial disease compared with placebo in patients with PsA and axial manifestations with inadequate response to NSAIDs.Trial registration numberNCT02721966.

ObjectiveTo investigate the effect of age at growth hormone (GH) treatment start on near adult height (NAH) in children with isolated GH deficiency (GHD).DesignNordiNet® International Outcome Study (IOS) (Nbib960128), a non-interventional, multicentre study, evaluates the long-term effectiveness and safety of Norditropin® (somatropin) (Novo Nordisk A/S) in the real-life clinical setting.MethodsPatients (n = 172) treated to NAH (height at ≥18 years, or height velocity <2 cm/year at ≥16 (boys) or ≥15 (girls) years) were grouped by age (years) at treatment start (early (girls, <8; boys, <9), intermediate (girls, 8–10; boys, 9–11) or late (girls, >10; boys, >11)) and GHD severity (<3 ng/mL or 3 to ≤10 ng/mL). Multiple regression analysis was used to evaluate the effect of age at treatment start (as a categorical and continuous variable) on NAH standard deviation score (SDS).ResultsAge at treatment start had a marked effect on NAH SDS; NAH SDS achieved by patients starting treatment early (n = 40 (boys, 70.0%); least squares mean (standard error) −0.76 (0.14)) exceeded that achieved by those starting later (intermediate, n = 42 (boys, 57.1%); −1.14 (0.15); late, n = 90 (boys, 68.9%); −1.21 (0.10)). Multiple regression analysis showed a significant association between NAH SDS and age at treatment start (P < 0.0242), baseline height SDS (HSDS) (P < 0.0001), target HSDS (P < 0.0001), and GHD severity (P = 0.0012). Most (78.5%) patients achieved a normal NAH irrespective of age at treatment start.ConclusionsEarly initiation of GH treatment in children with isolated GHD improves their chance of achieving their genetic height potential.

Summary Background Secukinumab is a fully human monoclonal antibody that selectively binds to and neutralizes interleukin‐17A. Objectives To assess the efficacy and safety of different maintenance dosing regimens of secukinumab 300 mg based on Psoriasis Area and Severity Index (PASI) response at week 24 in patients with moderate‐to‐severe plaque psoriasis. Methods OPTIMISE was a randomized, open‐label, rater‐blinded phase IIIb study. Patients (n = 1647) received secukinumab 300 mg at baseline; weeks 1, 2, 3 and 4; and every 4 weeks (q4w) to week 24. At week 24, PASI 90 responders (≥ 90% improvement in PASI; n = 1306) were randomized to secukinumab 300 mg q4w (n = 644) or q6w (n = 662) to week 52, and PASI ≥ 75 to < 90 responders (n = 206) were randomized to secukinumab 300 mg q4w (n = 114) or q2w (n = 92) to week 52. Results PASI 90 response was maintained at week 52 by 85·7% of patients with q4w dosing vs. 74·9% with q6w dosing (odds ratio 1·91, 95% confidence interval 1·44–2·55). The primary end point, noninferiority of q6w vs. q4w dosing, was not met. In PASI ≥ 75 to < 90 responders, the proportion of patients with PASI 90 response at week 52 was numerically higher in the q2w vs. the q4w group (57% vs. 46·5%, respectively, P = 0·10). Heavier patients (≥ 90 kg) demonstrated numerically higher PASI 90 response with the q2w (57·1%) vs. the q4w regimen (40%, P = 0·11). Conclusions Standard q4w dosing of secukinumab 300 mg is the optimal dosing regimen to achieve and maintain clear or almost clear skin. Patients with body weight ≥ 90 kg not achieving PASI 90 at week 24 may benefit from the q2w dosing regimen. What's already known about this topic? Individual responses to biologics in patients with psoriasis vary considerably and there may be a need to individualize treatment. Dose optimization strategies of currently available biologic drugs have been investigated mainly in rheumatic disorders. Secukinumab has shown long‐term PASI 90/100 responses (percentage improvement in Psoriasis Area and Severity Index) to year 5 in patients with moderate‐to‐severe plaque psoriasis when used at the dose of 300 mg every 4 weeks. What does this study add? Standard every 4 week (q4w) dosing of secukinumab 300 mg is the optimal regimen to achieve and maintain clear or almost clear skin at week 52; the majority of the patients (85·7%) maintain PASI 90 at week 52. Superiority of intensified (q2w) dosing over the q4w regimen could not be claimed. However, patients with a higher body weight (≥ 90 kg) not achieving PASI 90 response at week 24 may benefit from q2w dosing.

The use of appropriate growth standards/references is of significant clinical importance in assessing the height of children with short stature as it may determine eligibility for appropriate therapy. The aim of this study was to determine the impact of using World Health Organization (WHO) instead of national growth standards/references on height assessment in short children. Data were collected from routine clinical practice (1998–2014) from nine European countries that have available national growth references and were enrolled in NordiNet® International Outcome Study (IOS) (NCT00960128), a large-scale, non-interventional, multinational study. The patient cohort consisted of 5996 short pediatric patients diagnosed with growth hormone deficiency (GHD), Turner syndrome (TS) or born small for gestational age (SGA). The proportions of children with baseline height standard deviation score (SDS) below clinical cut-off values (–2 SDS for GHD and TS; –2.5 SDS for SGA) based on national growth references and WHO growth standards/references were compared for children aged <5 years and children aged ≥5 years. In seven of the countries evaluated, significantly fewer children aged ≥5 years with GHD (22%; P<0.0001), TS (21%; P<0.0001) or born SGA (32%; P<0.0001) had height below clinical cut-off values using WHO growth references vs. national references. Likewise, among children aged <5 years in the pooled analysis of the same seven countries, a significantly lower proportion of children with GHD (8%; P<0.0001), TS (12%; P = 0.0003) or born SGA (12%; P<0.0001) had height below clinical cut-off values using WHO growth standards vs. national references. In conclusion, in NordiNet® IOS the number of patients misclassified using WHO growth standards/references was significantly higher than with national references. This study highlights that, although no growth reference has 100% sensitivity for identifying growth disorders, the most recent national or regional growth charts may offer the most appropriate tool for monitoring childhood growth in Europe.

BackgroundSecukinumab (SEC) has provided significant and sustained improvement in the signs and symptoms of active psoriatic arthritis (PsA) and ankylosing spondylitis 1. Evidence on the efficacy of biologics in the treatment of PsA patients (pts) with axial manifestations affecting 30–70% of PsA pts is limited2, particularly as validated classification criteria for this subtype of PsA are not yet available; an effort to develop criteria is being undertaken by ASAS/GRAPPA. MAXIMISE is an ongoing study evaluating the efficacy and safety of secukinumab 300 or 150mg in managing axial manifestations in PsA ptsObjectivesTo report the primary analysis results at Week (Wk) 12 from MAXIMISE (NCT02721966) trialMethodsThis phase 3b, double blind, placebo (PBO)-controlled, multicentre 52-wk trial included 498 pts (aged ≥18 years) with PsA (CASPAR criteria), clinician-diagnosed axial involvements, spinal pain VAS >40/100 and BASDAI >4 despite trial of at least two NSAIDs. Pts were randomised to subcutaneous (SC) SEC (300/150 mg) or PBO weekly for 4 wks and every 4 wks thereafter. At Wk 12, PBO pts were re-randomised to SC SEC 300/150 mg. The primary endpoint was proportion of pts achieving ASAS20 response with SEC 300 mg at Wk 12. The key secondary endpoint was ASAS20 response with SEC 150 mg at Wk 12 after superiority of 300 mg was established. Analyses used multiple imputationResultsDemographic and baseline (BL) disease characteristics were comparable across groups (Table). Primary and key secondary endpoints were met; ASAS20 response rates at Wk 12 were 63.1% (SEC 300 mg; P<0.0001) and 66.3% (150 mg; P<0.0001) vs 31.3% (PBO; Figure). ASAS20 responses in pts using concomitant MTX were 65.1% [300 mg], 67.3% [150 mg] vs 33.9% [PBO] and corresponding values in No MTX group were 60.5%, 64.4% vs 27.1%. The safety profile was similar across groups through Wk 12ConclusionMAXIMISE is the first randomised controlled trial evaluating the efficacy of a biologic in the management of the axial manifestations of PsA. SEC 300 and 150 mg provided rapid and significant improvement in ASAS20 responses through Wk 12 in PsA pts with axial manifestations and inadequate responses to NSAIDsReferences[1] Lubrano E and Perrotta FM. Ther Clin Risk Manag. 2016;12:1587-92[2] Feld J, et al. Rheum Rev.2018;14:363 Demographics/BL Characteristics Mean (SD) unless specified SEC300 mg SC(N = 167) SEC150 mg SC(N = 165) PBO(N = 166) Age (yrs) 46.2 (12.3)46.9 (11.5) 46.6 (11.5) Male, n (%) 77 (46.1) 81 (49.1) 88 (53.0) Evidence of current psoriasis, n (%) 152 (91.0)147 (89.1)153 (92.2) Time since first axial symptoms (yrs) 6.8 (7.7)7.4 (7.6)7.7 (9.5) Total back pain score, VAS 72.5 (13.8)73.6 (15.3) 74.0 (13.7) Inflammatory back pain parameters, n (%) Onset of back pain is insidious 150 (89.8) 147 (89.1) 152 (91.6) Back pain improving with exercise 148 (88.6) 139 (84.2) 146 (88.0) Back pain worsening with rest 152 (91.0) 151 (91.5) 157 (94.6) Night pain with improvement upon getting up 147 (88.0) 147 (89.1) 143 (86.1) Awakening due to back pain in 2nd ...