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Objectives To evaluate the efficacy and safety of certolizumab pegol (CZP) after 24 weeks in RAPID-PsA (NCT01087788), an ongoing Phase 3 trial in patients with psoriatic arthritis (PsA). Methods Patients were randomised 1:1:1 to placebo, 200 mg CZP every 2 weeks (Q2W) or 400 mg CZP every 4 weeks (Q4W). Patients could have had exposure to one previous tumour necrosis factor (TNF) inhibitor therapy. Primary endpoints were American College of Rheumatology 20% (ACR20) response at week 12 and modified Total Sharp Score change from baseline at week 24. Secondary endpoints included; Psoriatic Arthritis Response Criteria (PsARC) score, Health Assessment Questionnaire Disability Index (HAQ-DI), Psoriasis Area and Severity Index, Leeds Enthesitis Index, Leeds Dactylitis Index, and Modified Nail Psoriasis Severity Index. Results Of 409 patients randomised, 368 completed 24 weeks of treatment. ACR20 response was significantly greater in CZP 200 mg Q2W and 400 mg Q4W-treated patients than placebo (58.0% and 51.9% vs 24.3% (p<0.001)) at week 12, with improvements observed by week 1. There was a statistically significant improvement in physical function from baseline, measured by HAQ-DI in CZP patients compared with placebo (−0.50 vs −0.19, p<0.001) and more patients treated with CZP 200 mg Q2W and CZP 400 mg achieved an improvement in PsARC at week 24 than placebo (78.3% and 77.0% vs 33.1% (p<0.001)). Sustained improvements were observed in psoriatic skin involvement, enthesitis, dactylitis and nail disease. Higher ACR20 response with CZP was independent of prior TNF inhibitor exposure. No new safety signals were observed. Conclusions Rapid improvements in the signs and symptoms of PsA, including joints, skin, enthesitis, dactylitis and nail disease were observed across both CZP dosing regimens.

Objectives To report the effect of different imputation methodologies on the assessment of radiographic progression in clinical trials. Methods The 216-week RAPID-psoriatic arthritis (PsA) (NCT01087788) trial of certolizumab pegol (CZP) in patients with active PsA was double-blind and placebo-controlled until week 24. A primary end point was change from baseline in modified Total Sharp Score(s) (mTSS). Prespecified imputation methodology in patients with fewer than two analysable mTSS used minimum observed baseline score for missing baseline values and maximum observed week 24 score for missing week 24 values. Post hoc analyses used alternative methods of imputation in patients with fewer than two analysable mTSS. mTSS non-progressors were defined as patients with ≤0 (predefined) or ≤0.5 (post hoc) change in mTSS from baseline to week 24. Baseline mTSS and C-reactive protein levels as predictors of radiographic progression were investigated. Results 409 patients were randomised. Baseline demographics were similar between groups. Prespecified imputation analysis inappropriately overestimated radiographic progression (least squares mean placebo, 28.9; CZP, 18.3; p≥0.05). Multiple post hoc analyses demonstrated that CZP inhibited radiographic progression compared with placebo, particularly in patients with high baseline mTSS and C-reactive protein levels. mTSS non-progression rate was higher in CZP than placebo groups in all analyses. Conclusions Inappropriate prespecified imputation methodology resulted in an unrealistic assessment of progression in all arms. Methodologies for imputing missing radiographic data can greatly affect assessment and reporting of mTSS progression.

Background Certolizumab pegol (CZP) is a PEGylated Fc-free anti-TNF that improves patient-reported outcomes (PROs) in rheumatoid arthritis.1 The efficacy and safety of CZP in psoriatic arthritis (PsA) has been investigated in RAPID-PsA (NCT01087788).2 Objectives To report the effect of CZP on PROs in PsA patients (pts), with and without prior anti-TNF exposure. Methods The ongoing 158-week (wk) Phase 3 RAPID-PsA trial was double-blind and placebo (PBO)-controlled to Wk24.2 Recruited pts had active PsA, had failed ≥1 DMARD, and could have experienced secondary failure to 1 prior anti-TNF. Pts were randomized 1:1:1 to PBO every 2 wks (Q2W), or 400mg CZP at Wk0, 2 and 4 (loading dose) followed by either 200mg CZP Q2W or 400mg CZP every 4 wks (Q4W). Primary efficacy endpoints were ACR20 response at Wk12 and change from baseline (BL) to Wk24 in the van der Heijde modified Total Sharp Score. PRO measures evaluated: fatigue assessment scale (FAS), patient assessment of pain (VAS), health assessment questionnaire-disability index (HAQ-DI), health-related quality of life (HRQoL) measured by the SF-36 (physical component summary (PCS), mental component summary (MCS) scores and domain scores), PsAQoL, and Dermatology Life Quality Index (DLQI). Post-hoc analyses of PRO in pts with and without prior anti-TNF exposure were conducted. Change from BL for all PROs was analyzed for the randomized population using analysis of covariance, with LOCF imputation. Results 409 pts were randomized. 20% of pts had received a prior anti-TNF. BL demographics were similar between groups. Significant differences in pain, fatigue, HAQ-DI, HRQoL (SF-36 PCS, MCS and all domain scores), PsAQoL, and DLQI were observed in both CZP arms vs PBO (p<0.001), irrespective of prior anti-TNF exposure (Table). Pain was significantly improved from Wk1, and fatigue and HAQ-DI from Wk2. More pts on CZP reached SF-36 general population norms than PBO pts. Image/graph Conclusions Both CZP dosing schedules effectively improved multiple PROs in pts with PsA across many facets of the disease. Rapid improvements were observed in pain, fatigue and HAQ-DI. The benefits of CZP treatment on physical and emotional components of HRQoL were seen across generic, PsA-specific and dermatology-specific measures. These benefits were seen in pts regardless of prior anti-TNF exposure. References Strand VS. Ann Rheum Dis 2011;70(6):996-1002, Mease P. Ann Rheum Dis 2012;71(Suppl3):150 Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma. Disclosure of Interest D. Gladman Grant/research support from: Abbott, BMS, Celgene, Johnson & Johnson, MSD, Novartis, Pfizer, UCB Pharma, Consultant for: Abbott, BMS, Celgene, Johnson & Johnson, MSD, Novartis, Pfizer, UCB Pharma, R. Fleischmann Grant/research support from: Genetech Inc, Roche, Abbott, Amgen, UCB Pharma, Pfizer, BMS, Lilly, Sanofi-Aventis, Lexicon, MSD, Novartis, BiogenIdec, Astellas, AstraZeneca, Janssen, Consultant for: Roche, Abbott, Amgen, UCB Pharma, Pfizer, BMS, Lilly, Sanofi-Aventis, Lexicon, Novartis, Astellas, AstraZeneca, Janssen, HGS, G. Coteur Employee of: UCB Pharma, F. Woltering Shareholder of: UCB Pharma, Employee of: UCB Pharma, P. Mease Grant/research support from: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Consultant for: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Speakers bureau: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma

Background Axial spondyloarthritis (axSpA) includes both ankylosing spondylitis (AS) and axSpA with no definitive sacroiliitis on X-ray (non-radiographic axSpA, nr-axSpA). These patients (pts) subgroups have similar clinical disease burden,1 however, the comparative health related Quality of Life (HRQoL) burden of these subgroups has been poorly researched. RAPID-axSpA (NCT01087762) investigated the effect of certolizumab pegol (CZP), a PEGylated Fc-free anti-TNF, which improves pt-reported outcomes (PROs) in rheumatoid arthritis,2 in axSpA. Objectives To report the effect of CZP on PROs in axSpA, including AS and nr-axSpA pts. Methods The ongoing 158-week (wk) Phase 3 RAPID-axSpA trial is double-blind and placebo (PBO)-controlled to Wk24.3 Recruited pts had adult-onset active axSpA according to the ASAS criteria,4 and included AS pts also meeting the modified New York criteria and nr-axSpA pts. Pts were randomized 1:1:1 to PBO every 2 wks (Q2W), or 400mg CZP at Wk0, 2 and 4 (loading dose) followed by either 200mg CZP Q2W or 400mg CZP every 4 wks (Q4W). The primary endpoint was ASAS20 response at Wk12. Secondary PRO measures included physical function (BASFI), total back pain (NRS) and a daily pain diary to Wk4, fatigue (NRS from BASDAI), Ankylosing Spondylitis Quality of Life (AsQoL), and SF-36. Other PRO measures were Sleep Problems Index II domains of the MOS Sleep scale (MOS-SPI) and SF-36 domains. All PROs were analyzed in the full analysis set using analysis of covariance on change from baseline (BL) with LOCF imputation. Results 325 pts were randomized. BL characteristics were similar between groups. Improvements in the CZP-treated arms were observed in pain NRS, fatigue NRS, BASFI and AsQoL from the first measurement at Wk1 through to Wk24 compared to PBO. Spinal pain was improved as early as day 2 after initiation of CZP compared to PBO. Pts in both CZP-treated dosage arms had greater improvements in MOS-SPI, SF-36 PCS, SF-36 MCS and SF-36 domains compared to PBO. More pts on CZP reached general population norms for SF-36 than pts on PBO. CZP had a similar impact on pain, fatigue and AsQoL in AS and nr-axSpA pts (Table). Relative to PBO pts, CZP treated nr-axSpA pts demonstrated a greater improvement in BASFI and sleep compared to AS pts (Table), and were more likely to reach population norms for SF-36. Image/graph Conclusions Both CZP dosing schedules rapidly improved all PRO including pain, fatigue, physical function and HRQoL of axSpA, in both AS and nr-axSpA pts. References Rudwaleit M. Arthritis Rheum 2009;60(3):717-727, Strand VS. Ann Rheum Dis 2011;70(6):996-1002, Landewé R. Arthritis Rheum 2012;64(10):336-337, Rudwaleit M. Ann Rheum Dis 2009;68(6):777-783 Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma. Disclosure of Interest J. Sieper Consultant for: Abbott, Merck, Pfizer, UCB Pharma, Novartis, Lilly, Janssen, Speakers bureau: Abbott, Merck, Pfizer, UCB Pharma, Novartis, Lilly, Janssen, A. Kivitz Grant/research support from: Abbott, Pfizer, Merck, Janssen, Consultant for: Abbott, Pfizer, Merck, Janssen, A. van Tubergen Grant/research support from: Abbott, MSD, Pfizer, Roche, Consultant for: Abbott, Pfizer, UCB Pharma, Speakers bureau: Abbott, MSD, UCB Pharma, A. Deodhar Consultant for: UCB Pharma, G. Coteur Employee of: UCB Pharma, F. Woltering Shareholder of: UCB Pharma, Employee of: UCB Pharma, R. Landewé Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth, Consultant for: Abbott, Ablynx, Amgen, AstraZeneca, BMS, Centocor, GSK, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth, Speakers bureau: Abbott, Amgen, BMS, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth

Background Certolizumab pegol (CZP) is a PEGylated humanized Fc-free anti-TNF that is clinically effective in rheumatoid arthritis [1]; this is the first report of clinical efficacy and safety of CZP in psoriatic arthritis (PsA). Objectives To assess efficacy and safety of CZP in patients (pts) with active PsA. Methods Pts with active PsA who had failed ≥1 DMARD and could have failed ≤1 anti-TNF were randomised 1:1:1 to placebo (PBO), or 400mg CZP at week (Wk) 0, 2 and 4 (loading dose, LD) followed by either 200mg CZP Q2W or 400mg CZP Q4W. Pts receiving PBO who failed to achieve a ≥10% decrease in TJC and SJC at both Wks14 and 16 were rescued and randomized at Wk16 to receive CZP 200mg Q2W or CZP 400mg Q4W following LD. The clinical primary endpoint was ACR20 response at Wk12. Non-responder imputation (NRI) was used for ACR and PASI75 responses; last observation carried forward (LOCF) for HAQ. Results 409 pts were randomized. Baseline demographics were similar between the 3 groups; 20% of pts had failed an anti-TNF. ACR20 response at Wk12 was significantly higher in both CZP arms vs PBO (Figure); the majority of the overall response rate observed at Wk24 was achieved by Wk12. Response with CZP was rapid, with a greater ACR20 response as early as Wk1 (7.4% for PBO vs 21.0% for CZP 200mg [p=0.001] and vs 23.0% for CZP 400mg [p<0.001]). At Wks12 and 24, both CZP arms showed significantly greater improvements than PBO in ACR50 and 70 (Figure). Greater improvements were also observed for both CZP arms in PASI75 (Figure), as well as in HAQ-DI at Wk 24 (HAQ-DI change from baseline; -0.50 [CZP combined] vs. -0.19 [PBO], p<0.001). Adverse events (AEs) occurred at the rates of 68% vs. 62% and serious AEs at 4% vs. 7% in PBO vs.CZP (combined dose), respectively. Two deaths occurred, one sudden death of unknown cause (CZP 400mg Q4W) and one myocardial infarct (CZP 200mg Q2W). The safety profile was similar to that observed with CZP in RA. Conclusions CZP effectively improved the signs and symptoms of arthritis, physical function and skin manifestations of psoriasis in pts with PsA with a safety profile similar to what has been observed in RA. References Mease PJ. Rheumatology 2011;50(2):261-70 Disclosure of Interest P. Mease Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, Speakers Bureau: UCB Pharma, R. Fleischmann Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, A. Deodhar Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, J. Wollenhaupt Consultant for: UCB Pharma, Speakers Bureau: UCB Pharma, D. Kielar Shareholder of: UCB Pharma, Employee of: UCB Pharma, F. Woltering Shareholder of: UCB Pharma, Employee of: UCB Pharma, C. Stach Employee of: UCB Pharma, B. Hoepken Employee of: UCB Pharma, T. Arledge Employee of: UCB Pharma, D. van der Heijde Consultant for: UCB Pharma

Background RAPID-PsA (NCT01087788) investigates the efficacy and safety of certolizumab pegol (CZP) in psoriatic arthritis (PsA).1 Objectives To analyse radiographic progression in PsA patients (pts) in the RAPID-PsA study using different imputation methods and assess the treatment effect of CZP in pts with and without identified baseline (BL) risk factors for progression. Methods The ongoing 158-week (wk) RAPID-PsA trial recruited pts with active PsA who failed ≥1 DMARD. Pts were randomized 1:1:1 to placebo (PBO), CZP 400mg Q4W or 200mg Q2W following loading dose. Data was evaluated in the Randomized Set. Radiographic progression analyses were assessed at Wk24 using the modified Total Sharp Score (mTSS, primary end point). The pre-specified imputation for change from baseline (CFB) in mTSS for pts with <2 analyzable X-rays used minimum observed BL score (0) and maximum observed Wk24 score (365.5) for missing values. Post-hoc analyses used alternative methods of imputation for pts with <2 analyzable X-rays including no imputation, imputation with the median, or mean CFB mTSS. The same post-hoc imputation approach was used to calculate % non-progressors at Wk24 (mTSS ≤0.5). Inhibition of radiographic progression was also analyzed according to BL mTSS (≤ or > median) and BL CRP levels (≤ or >15mg/L). Results 409pts were randomized. BL demographics were similar between groups. The pre-specified imputation analysis implausibly overestimated radiographic progression in all arms including PBO (Table). Post-hoc conventional analyses showed that CZP inhibited radiographic progression compared to PBO (Table). Pts with mTSS ≤6 (median score) or CRP ≤15mg/L at BL showed little radiographic progression in both the CZP and PBO groups. CZP (combined dose arm) decreased radiographic progression, vs PBO, in pts with BL mTSS >6 (0.08 vs 0.54, p<0.01) or CRP >15mg/L (0.08 vs 0.51, p<0.05). Higher BL mTSS and elevated CRP were also associated with a higher rate of non-progression in CZP vs PBO groups (95.1 vs 74.1 and 96.2 vs 78.3 for BL mTSS >6 and CRP >15mg/L, respectively). Image/graph Conclusions Pre-specified imputation overestimated radiographic progression in all treatment arms including PBO. Conventional imputation methods showed that CZP inhibited radiographic progression in PsA pts, particularly in pts with identified higher risk of progression. References Mease P. Ann Rheum Dis 2012;71(Suppl3):150 Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma. Disclosure of Interest D. van der Heijde Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB Pharma, Vertex, Consultant for: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB Pharma, Vertex, Employee of: Imaging Rheumatology bv., R. Fleischmann Grant/research support from: Genetech Inc, Roche, Abbott, Amgen, UCB Pharma, Pfizer, BMS, Lilly, Sanofi-Aventis, Lexicon, MSD, Novartis, BiogenIdec, Astellas, AstraZeneca, Janssen, Consultant for: Roche, Abbott, Amgen, UCB Pharma, Pfizer, BMS, Lilly, Sanofi-Aventis, Lexicon, Novartis, Astellas, AstraZeneca, Janssen, HGS, J. Wollenhaupt Grant/research support from: UCB Pharma, Consultant for: UCB Pharma, A. Deodhar Grant/research support from: UCB Pharma, Abbott, Amgen, Janssen, Novartis, Consultant for: UCB Pharma, Abbott, Speakers bureau: Abbott, Novartis, D. Kielar Shareholder of: UCB Pharma, Employee of: UCB Pharma, F. Woltering Shareholder of: UCB Pharma, Employee of: UCB Pharma, C. Stach Shareholder of: UCB Pharma, Employee of: UCB Pharma, B. Hoepken Shareholder of: UCB Pharma, Employee of: UCB Pharma, T. Arledge Shareholder of: UCB Pharma, Employee of: UCB Pharma, P. Mease Grant/research support from: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Consultant for: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma

Background Certolizumab pegol (CZP), a PEGylated Fc-free anti-TNF, has shown efficacy in reducing signs and symptoms of psoriatic arthritis (PsA) in RAPID-PsA (NCT01087788).1 Objectives To report the efficacy of CZP in PsA patients (pts) with and without prior anti-TNF exposure and to assess the impact of level of baseline skin involvement on PASI response. Methods The ongoing 158-week (wk) Phase 3 RAPID-PsA trial is double-blind and placebo (PBO)-controlled to Wk24.1 Recruited pts had active PsA, had failed ≥1 DMARD and could have experienced secondary failure to 1 prior anti-TNF. Pts were randomized 1:1:1 to PBO every 2 wks (Q2W), or 400mg CZP at Wk0, 2 and 4 (loading dose) followed by either 200mg CZP Q2W or 400mg CZP every 4 wks (Q4W). Clinical primary endpoint was ACR20 at Wk12. ACR20 was also investigated for pts with and without prior anti-TNF exposure. PASI responses were measured in pts with ≥3% body surface area skin involvement at baseline (BL). Post-hoc analyses of PASI response by BL PASI score (BL PASI <10 vs ≥10) were conducted. NRI was used for ACR and PASI responses. Analyses were performed on the Randomized Set (RS). Results 409 pts were randomized. BL demographics were similar between groups. 19.1% and 19.8% of PBO and CZP (combined arms) pts received prior anti-TNF. ACR20 at Wk12 was significantly higher in the CZP 200mg Q2W and CZP 400mg Q4W arms vs PBO (58.0% and 51.9% vs 24.3% [p<0.001 for both]) and was observed as early as Wk1.1 At Wk24, PASI75 response in pts with skin involvement (61.6% of RS) was 62.2% with CZP 200mg Q2W and 60.5% with CZP 400mg Q4W vs 15.1% PBO (p<0.001 for both). PASI75 and PASI90 at Wk12 and 24 was higher in pts with PASI ≥10 at BL vs <10 (Figure). ACR20 at Wk24 was similar between CZP 200mg Q2W and CZP 400mg Q4W arms, and greater vs PBO both in pts with (61.3% and 56.5% vs 11.5%) and without (64.5% and 56.3% vs 26.4%) prior anti-TNF exposure. Adverse events (AEs) occurred in 62% vs 68%, and serious AEs in 7% vs 4%, in CZP (combined arms) vs PBO pts, respectively. Two deaths occurred up to Wk24, one sudden death of unknown cause (CZP 400mg Q4W) and one myocardial infarct (CZP 200mg Q2W). No new safety signals were observed. Image/graph Conclusions Rapid improvements in the signs and symptoms of PsA and skin manifestations of psoriasis were observed across both CZP dosing regimens. Pts with higher BL PASI were more likely to achieve a PASI75 and PASI90 response. Similar ACR response rates with CZP were observed in pts with and without prior anti-TNF exposure. References Mease P. Arthritis Rheum 2012;64(10):1107 Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma. Disclosure of Interest P. Mease Grant/research support from: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Consultant for: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Speakers bureau: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, R. Fleischmann Grant/research support from: Genetech Inc, Roche, Abbott, Amgen, UCB Pharma, Pfizer, Bristol Myers Squibb, Lilly, Sanofi Aventis, Lexicon, MSD, Novartis, BiogenIdec, Astellas, Astra-Zeneca, Jansen, Consultant for: Roche, Abbott, Amgen, UCB Pharma, Pfizer, BMS, Lilly, Sanofi Aventis, Lexicon, Novartis, Astellas, Astra-Zeneca, Jansen, HGS, J. Wollenhaupt Consultant for: UCB Pharma, A. Deodar Grant/research support from: UCB Pharma, Abbott, Amgen, Janssen, Novartis, Consultant for: UCB Pharma, Abbott, Speakers bureau: Abbott, Novartis, D. Kielar Shareholder of: UCB Pharma, Employee of: UCB Pharma, F. Woltering Shareholder of: UCB Pharma, Employee of: UCB Pharma, C. Stach Shareholder of: UCB Pharma, Employee of: UCB Pharma, B. Hoepken: None Declared, T. Arledge Shareholder of: UCB Pharma, Employee of: UCB Pharma, D. van der Heijde Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli-Lilly, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Vertex., Consultant for: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli-Lilly, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Vertex., Employee of: Imaging Rheumatology bv

Background: Muscle-specific tyrosine kinase (MuSK) autoantibody-positive (Ab+) generalised myasthenia gravis (gMG) is a rare and frequently severe subtype of gMG. Objectives: To assess the efficacy and safety of rozanolixizumab in the subgroup of patients with MuSK Ab+ gMG in the MycarinG study. Design: A randomised, double-blind, placebo-controlled phase III study. Methods: Patients with acetylcholine receptor (AChR) Ab+ or MuSK Ab+ gMG (aged ⩾18 years, Myasthenia Gravis Foundation of America Disease Class II–IVa, Myasthenia Gravis Activities of Daily Living [MG-‍ADL] score ⩾3.0 [non-ocular symptoms], Quantitative Myasthenia Gravis score ⩾11.0) were randomly assigned (1:1:1) to receive once-weekly subcutaneous infusions of rozanolixizumab 7 mg/kg, rozanolixizumab 10 mg/kg or placebo for 6 weeks, followed by an 8-week observation period. Randomisation was stratified by AChR and MuSK autoantibody status. The primary study endpoint was change from baseline to Day 43 in MG-ADL score. Treatment-emergent adverse events (TEAEs) were also assessed. Results: Overall, 200 patients were randomised, of whom 21 had MuSK Ab+ gMG and received rozanolixizumab 7 mg/kg (n = 5), 10 mg/kg (n = 8) or placebo (n = 8). In patients with MuSK Ab+ gMG, reductions from baseline to Day 43 in MG-ADL scores were observed: rozanolixizumab 7 mg/kg least squares mean (LSM) change (standard error), –7.28 (1.94); 10 mg/kg, –4.16 (1.78); and placebo, 2.28 (1.95). Rozanolixizumab 7 mg/kg LSM difference from placebo was −9.56 (97.5% confidence interval: −15.25, −3.87); 10 mg/kg, −6.45 (−11.03, –1.86). TEAEs were experienced by four (80.0%), five (62.5%) and three (37.5%) patients with MuSK Ab+ gMG receiving rozanolixizumab 7 mg/kg, 10 mg/kg and placebo, respectively. No patients experienced serious TEAEs. No deaths occurred. Conclusion: This subgroup analysis of adult patients with MuSK Ab+ gMG enrolled in the MycarinG study supports the use of rozanolixizumab as an effective treatment option for patients with gMG who have MuSK autoantibodies. Trial registration: ClinicalTrials.gov: NCT03971422 (https://clinicaltrials.gov/study/NCT03971422); EU Clinical Trials Register: EudraCT 2019-000968-18 (https://www.clinicaltrials‌register.eu/ctr-search/trial/2019-000968-18/GB). Plain language summary Rozanolixizumab improved symptoms in people with anti-muscle-specific tyrosine kinase antibody-positive generalised myasthenia gravis in the MycarinG clinical study Myasthenia gravis is a rare, chronic autoimmune disease affecting the communication between nerves and muscles. People with the disease experience fluctuating muscle weakness and fatigue, leading to problems with mobility, speaking, swallowing and breathing. The disease is called generalised when muscles other than those that move the eyes and eyelids are affected. It is caused by antibodies that attack a person’s own cells. Most people with the disease have antibodies against acetylcholine receptors (AChRs). However, some have antibodies against the muscle-specific tyrosine kinase (MuSK) protein and can experience more severe symptoms compared with people who have anti-AChR antibodies. Standard treatments for myasthenia gravis do not always work for people with anti-MuSK antibodies. The MycarinG study looked at whether rozanolixizumab was better than a placebo at treating the symptoms of adults with generalised myasthenia gravis and anti-AChR or anti-MuSK antibodies. Assessments measured disease severity and myasthenia gravis symptoms, such as physical fatigue, and how they affected daily activities. The study also looked at whether people receiving rozanolixizumab had any side effects. Here, we look at the group of people with anti-MuSK antibodies who took part in the MycarinG study. In total, 21 of the 200 people in the study had anti-MuSK antibodies. The symptoms of myasthenia gravis improved more in people with anti-MuSK antibodies who received rozanolixizumab than in those who received placebo. Common side effects with rozanolixizumab included headache, diarrhoea and feeling sick. No serious side effects were seen, and no patients died. The results show that rozanolixizumab is an effective treatment for people with generalised myasthenia gravis who have anti-MuSK antibodies. The results in this group of people are consistent with those seen in all people who took part in the study (with either antibody type).

Despite the weight of his work and his prominence in Arabic public debate, the Egyptian public intellectual ʿAbd al-Wahhab Elmessiri (1938–2008) has not been the subject of much serious study. In this article, I show that Elmessiri's oeuvre offers a rich and creative perspective on both Judaism and Zionism. Studying Elmessiri from the perspective of identity/alterity studies, I argue that his representation of Judaism qualifies as what Gerd Baumann and André Gingrich call “encompassment by hierarchical subsumption.” The article offers an analysis of the discursive logic behind this image of Judaism and its connection to Elmessiri's anti-Zionist agenda, rejection of anti-Semitism, and critique of Western modernity.

In this article I will answer the question why, in the Islamic world, Islamist activism finds the support that it apparently does among segments of the general public of the various countries. In particular, the initial elements and circumstances that induce a person to support or even join an Islamist group are the subject of this study. After defining the notion of Islamism in the first section, I shall give an assessment of the popularity of Islamism. Following upon this, the third section will show that the conditionalities which drive a person towards an Islamist inclination or conviction cannot in the main have anything to do with the Islamic religion per se. Lastly it will be argued that these conditionalities are rather to be found in a wide array of interacting political, social, historical and economic factors.