Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy and safety of Certolizumab Pegol (CZP) in subjects with adult onset active and progressive Psoriatic Arthritis (PsA).
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. (Table Presented).
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. 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.
Background Several new disease-specific composite disease activity measures have been developed for psoriatic arthritis (PsA). Objectives Using data from a randomized double-blind placebo-controlled trial of certolizumab pegol (CZP) in PsA (RAPID-PsA, NCT01087788) we aimed to compare the performance of the Psoriatic Arthritis Disease Activity Score (PASDAS), the Composite Psoriatic Disease Activity Index (CPDAI), and modifications of the CPDAI with the Disease Activity Score 28 (DAS28), which was developed for use in rheumatoid arthritis. Methods The CPDAI and PASDAS composite measures have been described previously.1,2 In RAPID-PsA not all components of CPDAI were collected, therefore psoriasis body surface area was substituted for Psoriasis Area Severity Index, and the Health Assessment Questionnaire was used as the function modifier for the axial component of this measure (CPDAIm). The CPDAI was further modified by the addition of a patient (pt)-completed outcome domain, based on the pt visual analogue scale scores for arthritis pain and global disease activity (CPDAIpro). The performance of these measures was assessed after 12 weeks of CZP treatment by calculating, for the change from baseline, the standardized response mean, the baseline-adjusted effect size compared to placebo (ESadj, based on analysis of covariance), and the required sample size based on the ESadj. Data are reported for those pts with all outcome components available. Only observed data were used, without imputation. Results The largest ESadj was found for PASDAS, followed by DAS28, CPDAIm and CPDAIpro (Table). These figures translated into differences in sample size estimation for further studies. Conclusions The PASDAS and CPDAI composite measures demonstrated good responsiveness and discriminative ability in this trial, supporting further exploration of their use in PsA clinical trials. Differences in the performance of these new PsA-specific composite measures were seen in this dataset. These results may help inform the selection of appropriate composite measures for PsA in future studies. Addition of a pt-completed outcome domain to the CPDAI did not appear to improve performance of the composite score. (Figure Presented).
<b>OBJECTIVES: </b>To report the effect of different imputation methodologies on the assessment of radiographic progression in clinical trials.<b>METHODS: </b>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.<b>RESULTS: </b>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.<b>CONCLUSIONS: </b>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.
<b>OBJECTIVES: </b>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).<b>METHODS: </b>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.<b>RESULTS: </b>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.<b>CONCLUSIONS: </b>Rapid improvements in the signs and symptoms of PsA, including joints, skin, enthesitis, dactylitis and nail disease were observed across both CZP dosing regimens.
<b>OBJECTIVE: </b>To examine the effect of certolizumab pegol (CZP) on patient-reported outcomes (PROs) in psoriatic arthritis (PsA) patients with and without prior tumor necrosis factor (TNF) inhibitor exposure.<b>METHODS: </b>The ongoing phase III RAPID-PsA trial was double blind and placebo controlled to week 24. Patients were randomized 1:1:1 to placebo every 2 weeks or CZP 400 mg at weeks 0, 2, and 4, followed by either CZP 200 mg every 2 weeks or CZP 400 mg every 4 weeks. PRO measures evaluated were the Health Assessment Questionnaire (HAQ) disability index (DI), health status (measured by the Short Form 36 [SF-36] health survey), Psoriatic Arthritis Quality of Life (PsAQOL), Fatigue Assessment Scale, patient assessment of pain (visual analog scale), and Dermatology Life Quality Index (DLQI). Post hoc analyses of PROs in patients with and without prior TNF inhibitor exposure were conducted. Change from baseline for all PROs was analyzed for the randomized population using analysis of covariance with last observation carried forward imputation.<b>RESULTS: </b>A total of 409 patients were randomized. Twenty percent had received a prior TNF inhibitor. Baseline demographics were similar between the treatment groups. At week 24, clinically meaningful differences in HAQ DI, SF-36, PsAQOL, fatigue, pain, and DLQI were observed in both CZP arms versus placebo (P < 0.001), irrespective of prior TNF inhibitor exposure. More CZP-treated patients reached SF-36 general population norms than placebo-treated patients.<b>CONCLUSION: </b>Both CZP dosing schedules provided rapid improvements in PROs across multiple disease aspects in patients with PsA. The benefits of CZP treatment for health-related quality of life were seen across generic, PsA-specific, and dermatology-specific measures and were observed in patients regardless of prior TNF inhibitor exposure.
Objectives: To examine the long-term effect of certolizumab pegol (CZP) on workplace and household productivity up to 96 weeks (wks) in patients with active psoriatic arthritis (PsA). Methods: The ongoing RAPID-PsA trial (NCT01087788) is double-blind and PBO-controlled to Wk24, dose-blind to Wk48 and open-label to Wk216. Patients had active PsA and had failed ≥ 1 DMARD. Patients originally randomized to CZP (200mg Q2W or 400mg Q4W, following 400mg loading dose [LD] at Wks 0, 2, 4) continued on their assigned dose in the OLE; PBO patients entering dose-blind phase were re-randomized to CZP LD followed by CZP 200mg Q2W or 400mg Q4W after Wk24 or, for non-responders, Wk16. The validated arthritis-specific Work Productivity Survey (WPS) administered Q4W from baseline (BL), assessed the impact of PsA on workplace and household productivity in the randomized set. WPS responses (LOCF imputation) in patients originally randomized to CZP groups are summarized descriptively over 96 wks. Results: 409 patients were randomized, of whom 273 received CZP 200mg Q2W or CZP 400mg Q4W. Of patients randomized to CZP, 91% completed Wk24, 87% Wk48 and 80% Wk96. In employed patients in both CZP groups (60.8% of all CZP patients at BL), decreases in absenteeism and presenteeism to Wk24 were continued up to Wk96 (BL: mean 2.0 and 1.6 days missed/ month in the CZP 200mg Q2W and 400mg Q4W groups, respectively; mean 5.2 and 5.1 days with reduced productivity/month vs Wk96: mean 0.3 and 0.4 days missed/ month; mean 0.7 and 1.5 days with reduced productivity/month). Improvements in household productivity and social participation reported in both CZP groups over 24 wks were also maintained to Wk96. Conclusions: The initial improvements with CZP in workplace and household productivity, and social participation were sustained up to 96 wks in PsA patients.
<b>OBJECTIVES: </b>To evaluate the effect of certolizumab pegol (CZP) on productivity outside and within the home, and on participation in family, social and leisure activities in adult patients with psoriatic arthritis (PsA).<b>METHODS: </b>RAPID-PsA (NCT01087788) is a phase 3, double-blind, placebo-controlled trial. 409 patients with active PsA were randomised 1:1:1 to placebo, CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg every 4 weeks (Q4W). The arthritis-specific Work Productivity Survey (WPS) assessed the impact of PsA on paid work and household productivity, and participation in social activities during the preceding month. WPS responses were compared between treatment arms using a non-parametric bootstrap-t method.<b>RESULTS: </b>At baseline, 56.6%, 60.1% and 61.5% of placebo, CZP 200 mg Q2W and CZP 400 mg Q4W patients were employed. By week 24, employed CZP patients reported an average of 1.0-1.8 and 3.0-3.9 fewer days of absenteeism and presenteeism, respectively, per month compared with 1.0 and 0.3 fewer days for placebo patients (p<0.05). Within the home, by week 24, CZP patients reported an average of 3.0-3.5 household work days gained per month versus 1.0 day for placebo (p<0.05). CZP patients also reported fewer days with reduced household productivity or days lost for participation in family, social and leisure activities. Improvements with CZP were seen as early as week 4 and continued to week 24.<b>CONCLUSIONS: </b>CZP treatment significantly improved productivity at paid work and within the home, and resulted in greater participation in social activities for PsA patients.<b>Trial Registration Number: </b>NCT01087788.
Background: Previous reports of the RAPID-PsA trial (NCT01087788) have demonstrated the efficacy of certolizumab pegol (CZP) in improving joint outcomes of psoriatic arthritis (PsA) over 96 weeks (wks) of treatment in patients (pts) with and without prior anti-TNF exposure.1,2 Objectives: To report the efficacy of CZP over 4 years for the treatment of joint outcomes in PsA pts with and without prior anti-TNF exposure. Methods: The RAPID-PsA trial was double-blind and placebo-controlled to Wk24, dose-blind to Wk48 and open-label (OL) to Wk216. Pts had active PsA, had failed ≥1 DMARD, and ≤40% pts could have received 1 prior anti-TNF. Pts originally randomized to CZP (200mg Q2W or 400mg Q4W, following 400mg loading dose at Wks 0, 2, 4) continued on their assigned dose in the OL period. Joint disease activity was assessed in all pts using tender joint count (TJC), swollen joint count (SJC) and DAS28(CRP), as well as the composite disease activity measures ACR20/50/70. Data are shown as observed case (OC) and with imputation: NRI for categorical and LOCF for continuous measures. Data are presented for all pts originally randomized to CZP with and without prior anti-TNF exposure. Results: 409 pts were randomized and 273 received CZP from Wk0 (54/273 pts had prior anti-TNF exposure). Of pts randomized to CZP at baseline, 91% completed to Wk24, 87% to Wk48 and 67% to Wk216. CZP treatment was associated with improvements in all measures of joint disease activity to Wk24. Improvements in outcomes including TJC, SJC and DAS28(CRP), as well as the composite measures ACR20/50/70, were sustained through to Wk216 of the trial and were similar in pts with and without prior anti-TNF exposure (Figure). Greater improvements were observed in those pts completing to Wk216, as expected (Figure, OC data). Pts experienced further improvements from Wk24 to Wk216 in the high-threshold outcome ACR70 when either OC or NRI was used (Table). At Wk216, ACR20 responses were similar regardless of dose regimen in pts with and without prior anti-TNF exposure (pts with anti-TNF exposure [OC]: 200mg Q2W: 81.8%; 400mg Q4W: 83.3%; pts without prior anti-TNF exposure [OC]: 200mg Q2W: 75.0%; 400mg Q4W: 85.3%). Conclusions: Improvements in measures of joint disease activity were observed in PsA pts to Wk24 and efficacy was sustained over 4 years. Efficacy remained similar in pts with and without prior anti-TNF exposure in all joint outcomes assessed. (Figure Presented).
Background: Extra-articular manifestations (EAMs) of psoriatic arthritis (PsA) include nail psoriasis, dactylitis, and enthesitis, which can significantly impact patients' (pts') quality of life.1 In the RAPID-PsA trial (NCT01087788), certolizumab pegol (CZP) improved the signs and symptoms of EAMs in pts with PsA over 96 weeks (wks).2 Objectives: To report improvements in EAMs of PsA in pts treated with CZP over 4 years, both with and without prior anti-TNF exposure. Methods: The RAPID-PsA trial was double-blind and placebo-controlled to Wk24, dose-blind to Wk48, and open-label (OL) to Wk216. Pts had active PsA and had failed ≥1 DMARD. Pts originally randomized to CZP (200mg Q2W or 400mg Q4W, following 400mg loading dose at Wks0, 2, 4) continued their assigned dose in the OL period. We present EAM data for those pts originally randomized to CZP, with involvement of the particular EAM at baseline (BL), and both with and without prior anti-TNF exposure. EAMs assessed include nail psoriasis (modified Nail Psoriasis Severity Index [mNAPSI], BL involvement = BL mNAPSI >0), enthesitis (Leeds Enthesitis Index [LEI], BL involvement = BL LEI >0), and dactylitis (Leeds Dactylitis Index [LDI], BL involvement = ≥1 digit affected with a difference in circumference ≥10% compared to the opposite digit). Also presented are the proportions of pts with BL involvement of each EAM who achieved total resolution of the respective EAM on follow-up (a score of 0 for mNAPSI, LEI, or LDI). Observed values are reported, combined for pts receiving either CZP dose regimen. Results: A total of 409 PsA pts were randomized; 273 received CZP from Wk0. Among CZP-randomized pts, 197 had nail psoriasis at BL (159 without, and 38 with, prior anti-TNF exposure), 172 had enthesitis (133 without, and 39 with, prior anti-TNF exposure), and 73 had dactylitis (56 without, and 17 with, prior anti-TNF exposure). Although relatively few pts were anti-TNF experienced, a large proportion of pts both with and without prior anti-TNF exposure with BL involvement went on to achieve total resolution of the respective EAM following 48 wks of CZP treatment (Table). Among pts completing the study, the proportions achieving total resolution were maintained or further increased from Wk48 to Wk216 (Table). Mean scores of all EAMs assessed showed improvements by Wk48 of CZP treatment in pts both with and without prior anti-TNF exposure, which were maintained to Wk216 in pts completing the study (Table). Conclusions: PsA patients treated with CZP for up to 4 years, both with and without prior anti-TNF exposure, exhibited sustained improvements in the extra-articular manifestations of PsA. (Figure Presented).
Background: In the RAPID-PsA trial (NCT01087788), certolizumab pegol (CZP) improved skin manifestations of psoriatic arthritis (PsA) over 96 weeks (wks). Here we report dermatologic outcomes over 4 years' of CZP treatment in patients (pts) with and without prior anti-TNF exposure. Methods: RAPID-PsA was double-blind and placebo-controlled to Wk24, dose-blind to Wk48 and open-label (OL) to Wk216. Pts had active PsA and had failed ≥1 DMARD;≤40% of pts could have received 1 prior anti-TNF. Pts randomized to CZP at baseline (BL; 200mg Q2Wor 400mg Q4W, following 400mg loading dose at Wks 0, 2, 4) continued their assigned dose in the OL period. The primary clinical outcome (ACR20 at Wk12) has been reported previously. We report dermatologic outcomes for CZP-randomized pts with ≥3% skin involvement at BL, for pts with and without prior anti-TNF exposure. Data are reported as observed case (OC) and with imputation: NRI for categorical outcomes, LOCF for continuous measures. Results: 273/409 randomized pts received CZP from Wk0; of these, 183 (67.0%) completed Wk216. The primary clinical variable showed relevant differences (Wk12 ACR20: 58.0%, 51.9% vs 24.3% for CZP 200mg Q2W, 400mg Q4W vs placebo [NRI]). ACR responses were maintained to Wk216 (ACR20: 54.3%, 54.8% for CZP 200mg Q4W, 400mg Q4W [NRI]). Of 166 pts with≥3% skin involvement at BL, 36 pts across CZP dose groups had prior anti-TNF exposure (mean PASI=11.8, meanDLQI=11.7), 130 were anti-TNF naïve (mean PASI = 12.1, mean DLQI = 11.1). Improvements in PASI responses observed to Wk96 were sustained to Wk216, both in pts with and without prior anti-TNF exposure (PASI75 with vs without prior anti-TNF: Wk96 = 69.2% vs 74.0%, Wk216 = 90.9% vs 75.9%). Improvements were maintained even when stringent NRI imputation was used (PASI75 with vs without prior anti-TNF: Wk96 = 50.0% vs 54.6%, Wk216 = 55.6% vs 50.8%). Similar sustained improvements occurred in mean PASI score (OC: with vs without prior anti-TNF: Wk96= 2.4 vs 1.7, Wk216 = 1.3 vs 2.0; LOCF imputed: with vs without prior anti-TNF: Wk96 = 2.4 vs 2.6, Wk216 = 2.4 vs 2.6), and the patient-reported measure DLQI (OC: mean with vs without prior anti-TNF: Wk96= 1.8 vs 3.2, Wk216=2.1 vs 3.1; LOCF imputed: mean with vs without prior anti-TNF: Wk96 = 2.9 vs 3.5, Wk216 = 3.5 vs 3.6). Conclusion: Improvements in joint and skin manifestations of PsA were maintained over 4 years' of CZP treatment. Skin outcomes were maintained in pts with and without prior anti-TNF exposure.
<b>OBJECTIVE: </b>Early identification of patients unlikely to achieve good long-term disease control with anti-tumor necrosis factor therapy in axial spondyloarthritis (SpA) and psoriatic arthritis (PsA) is important for physicians following treat-to-target recommendations. Here we assess associations between disease activity or clinical response during the first 12 weeks of treatment and attainment of treatment targets at week 48 in axial SpA and PsA patients receiving certolizumab pegol.<b>METHODS: </b>The relationship between disease activity or clinical response during the first 12 weeks of treatment and achievement of week-48 targets (for axial SpA: inactive disease based on Ankylosing Spondylitis Disease Activity Score [ASDAS] using the C-reactive protein [CRP] level, or Bath Ankylosing Spondylitis Disease Activity Index <2 with normal CRP level; and for PsA: minimal disease activity) was assessed post hoc using RAPID-axSpA and RAPID-PsA trial data.<b>RESULTS: </b>A clear relationship between disease activity from week 2 to 12 and achievement of week-48 treatment targets was observed in both axial SpA and PsA populations. In axial SpA, week-48 ASDAS inactive disease was achieved by 0% of patients (0 of 21) with ASDAS very high disease activity at week 12, compared to 68% of patients (34 of 50) with week-12 ASDAS inactive disease. For PsA, week-48 minimal disease activity was achieved by 0% of patients (0 of 26) with Disease Activity Score in 28 joints (DAS28) using the CRP level >5.1 at week 12, compared to 73% of patients (57 of 78) with DAS28-CRP <2.6. Similar results were observed regardless of the disease activity measure used. Clinical response at week 12 also predicted week-48 outcomes, though to a lesser extent than disease activity.<b>CONCLUSION: </b>Using disease activity and the clinical response state during the first 12 weeks of certolizumab pegol treatment, it was possible to identify a subset of axial SpA and PsA patients unlikely to achieve long-term treatment goals.
Background: The RAPID-PsA trial (NCT01087788) investigated the efficacy and safety of certolizumab pegol (CZP) in patients (pts) with psoriatic arthritis (PsA). It demonstrated that CZP treatment inhibits radiographic progression over 96 weeks (wks).1 Objectives: We report the long-term effect of CZP treatment on radiographic progression in pts with PsA over 4 years. Methods: The RAPID-PsA phase 3 trial was double-blind and placebo-controlled to Wk24, dose-blind to Wk48, and open-label (OL) to Wk216. Pts had active PsA and had failed ≥1 DMARD. Pts randomized to CZP (200mg Q2W or 400mg Q4W, following 400mg loading dose at Wks0, 2, 4) continued their assigned dose in the OL period. Radiographs taken at baseline (BL), and at Wks96, 168, 216, were read in a single reading campaign using the modified Total Sharp Score (mTSS) for PsA by 2 readers, blinded to patient information and time point sequence. The mean of the scores of the 2 readers was used. Outcomes reported are the least squares (LS) mean mTSS score, change from BL (CFB) in mTSS score, and the percentage of pts assessed for radiographic damage who achieved mTSS non-progression (defined either as CFB in mTSS score ≤0.5 or ≤0), for all Wk0 CZP-treated pts, irrespective of dose regimen. mTSS score and CFB were estimated using Mixed Model Repeated Measures (MMRM) estimates; proportions of pts with radiographic non-progression are presented as observed case. Results: 409 PsA pts were randomized, of whom 273 received CZP from Wk0. The LS mean BL mTSS score was 16.0 and there was little increase from BL in mTSS score to Wk216 (Table). Amongst those who completed the study to Wk216, the majority of CZP-treated pts achieved radiographic non-progression to Wk216, both with non-progression defined as CFB in mTSS score ≤0.5 or ≤0 (Table). The change in LS mean mTSS score over time for Wk0 CZP-treated pts was consistently low throughout the trial: 0.14 (95% CI: 0.02-0.26) per 48 wks from BL to Wk96, and 0.18 (95% CI: 0.08-0.28) per 48 wks from Wk96 to Wk216. Conclusions: There was little radiographic progression in CZP-treated PsA pts, as measured by mTSS, throughout the 4-year RAPID-PsA trial. (Table Presented).
Background: Psoriatic arthritis (PsA) is a heterogeneous inflammatory disease that has a substantial impact on patients' (pts) physical and emotional wellbeing.1 Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-TNF that has been shown to improve patient-reported outcomes (PROs) in pts with PsA over 96 weeks (wks) of treatment in the RAPID-PsA study (NCT01087788).2 Objectives: To investigate whether initial improvements in PROs observed with CZP treatment were maintained over 4 years in the RAPID-PsA study. Methods: RAPID-PsA was double-blind and placebo-controlled to Wk24, doseblind to Wk48, and open-label to Wk216. Pts were aged ≥18 years, with a diagnosis of active PsA, and had failed treatment with ≥1 DMARD. Pts originally randomized to CZP (400mg at Wks0,2,4 [loading dose] followed by either 200mg every 2 wks [Q2W] or 400mg every 4 wks [Q4W]) continued on their assigned dose during the open-label period. PROs assessed included Patient's Global Assessment of Arthritis Pain (PtAAP; visual analog scale), fatigue (numeric rating scale), Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 Physical and Mental Component Summary (SF-36 PCS/MCS), Psoriatic Arthritis Quality of Life (PsAQoL), and Dermatology Life Quality Index (DLQI; assessed in the subgroup of pts with ≥3% body surface area affected by psoriasis at baseline [BL]). Data are reported as the mean change from BL (CFB) for pts randomized to CZP at Wk0, with last observation carried forward (LOCF) imputation for Wk24, and LOCF imputation and observed case (OC) values for Wk216. Results: Of 273 pts randomized to CZP at Wk0, 248 (91%) completed Wk24 and 183 (67%) completed Wk216. Improvements observed to Wk24 of treatment were generally maintained over 4 years (to Wk216) in all PROs assessed, regardless of prior anti-TNF exposure (Table). Similar improvements were observed in both CZP dose regimens for all PROs examined, including PtAAP (CFB at Wk216 in the 200mg Q2W group [with LOCF imputation]: -30.5, in the 400mg Q4W group: -33.8); fatigue (-2.3, -2.3); HAQ-DI (-0.50, -0.49); SF-36 PCS (8.73, 8.77); SF-36 MCS (3.91, 3.28); PsAQoL (-4.6, -4.4); and DLQI (-8.4, -6.8). Conclusions: Early improvements with CZP treatment were maintained over 4 years in all PROs assessed in the RAPID-PsA study. Similar improvements were observed in pts with and without prior anti-TNF exposure, and in both CZP dose regimens. (Figure Presented).
Background: In RAPID-PsA (NCT01087788) certolizumab pegol (CZP) improved signs and symptoms of psoriatic arthritis (PsA) over 4-years' treatment. Here we report short- and long-term efficacy of CZP with and without concomitant DMARD use, including effects on extra-articular manifestations of the disease (EAMs). Methods: RAPID-PsA was double-blind and placebo-controlled to Week (Wk)24, dose-blind to Wk48 and open-label (OL) to Wk216. Patients (pts) had active PsA with ≥1 failed DMARD. Wk0 CZP-randomized pts (200mg Q2W or 400mg Q4W, following 400mg loading dose at Wks 0, 2, 4) continued their assigned dose in OL. We report efficacy to Wk216 for pts receiving CZP from Wk0 (dose combined) with and without DMARD use at baseline (BL; DMARD+ and DMARD). Outcomes included ACR20, Psoriasis Area Severity Index (PASI), Leeds Enthesitis Index (LEI), and Leeds Dactylitis Index (LDI) in pts with involvement of the respective EAM at BL (psoriasis: BSA ≥3%; enthesitis: LEI>0; dactylitis: ≥1 digit affected and LDI ≥0). Data are observed case (OC) and imputed: NRI for dichotomous outcomes and LOCF for quantitative data. Results: 273 pts received CZP from Wk0. 74 (27.1%) CZP pts were DMARD, 6 (8.1%) of whom initiated a new DMARD during the study. 8 DMARD+ pts (4.0%) increased, 29 (14.6%) reduced/discontinued and 13 (6.5%) increased and reduced/discontinued DMARD use. 141 (70.9%) DMARD+ and 42 (56.8%) DMARD pts completed Wk216. Efficacy of CZP in both DMARD+ and DMARD pts was maintained over 4 years (NRI [OC]: DMARD+: ACR20 at Wk24 = 62.8%, at Wk216 = 57.3% [79.7%]; DMARD: ACR20 at Wk24 = 52.7%, at Wk216 = 47.3% [83.3%]). Among DMARD+ and DMARD pts, at BL, 113 and 53 (56.8%; 71.6%) had psoriasis (mean PASI = 11.4; 13.3), 125 and 47 (62.8%; 63.5%) enthesitis (mean LEI = 3.1; 2.7), and 47 and 20 (23.6%; 27.0%) dactylitis (mean LDI = 54.3; 59.7). Improvements in EAMs at Wk24 were maintained to Wk216 in both DMARD+ and DMARD pts (imputed [OC]: DMARD+ pts: mean PASI at Wk24 = 2.6, at Wk216 = 2.3 [1.7]; PASI75 at Wk24 = 57.5%, at Wk216 = 54.0% [79.2%]; mean LEI at Wk24 = 1.0, at Wk216 = 0.8 [0.6]; mean LDI at Wk24 = 3.7, at Wk216 = 4.3 [0.4]; DMARD pts: mean PASI at Wk24 = 2.9, at Wk216 = 3.2 [2.2]; PASI75 at Wk24 = 69.8%, at Wk216 = 47.2% [78.1%]; mean LEI at Wk24=1.0, at Wk216 =0.9 [0.2]; mean LDI at Wk24=5.7, at Wk216 = 3.7 [2.5]). Conclusion: Pts completing RAPID-PsA, treated with CZP both with and without concomitant DMARD use, showed sustained improvements in their disease, maintained over 4 years.
<b>OBJECTIVE: </b>The product of physician's global assessment and body surface area (PGA×BSA) to assess psoriasis severity has previously been investigated in patients with psoriasis, with the aim of assessing PGA×BSA as an alternative to the time-consuming Psoriasis Area and Severity Index (PASI). Here, we investigate PGA×BSA as an alternative to PASI in patients with psoriatic arthritis (PsA).<b>METHODS: </b>Analyses used data from the double-blind, placebo-controlled, RAPID-PsA trial (NCT01087788) that investigated the efficacy of certolizumab pegol (CZP) in patients with PsA. Outcomes assessed whether the PGA×BSA and PASI results were comparable, and whether these outcomes correlated with one another or with the Dermatology Life Quality Index (DLQI).<b>RESULTS: </b>For CZP-treated patients, both PGA×BSA and PASI demonstrated similar sensitivities to treatment between baseline and Week 24, with mean improvements of 77.4% and 69.0%, respectively. Similar improvements were also seen with placebo (PGA×BSA: 3.2%, PASI: 6.1%). Achievement of 75% response criterion in PGA×BSA and PASI was attained by similar proportions of patients with CZP (PGA×BSA75: 59.0%, PASI75: 61.4%) and placebo (PGA × BSA75: 15.1%, PASI75: 15.1%). Cross tabulations showed high concordance between achievement of response outcomes in PGA×BSA and PASI (79.6-95.2%). Spearman correlations revealed strong correlations between PGA×BSA and PASI at baseline (r = 0.78; n = 225) and percentage improvement to Week 24 (r = 0.85; n = 186). Both outcomes were only moderately correlated with DLQI (r = 0.41-0.50; n = 179-249).<b>CONCLUSION: </b>PGA×BSA is sensitive to changes in skin manifestations in patients with PsA treated with CZP. Further, PGA×BSA correlates strongly with PASI, and achievement of 75% improvement was similar for PGA×BSA and PASI.
Objective To report the efficacy, patient-reported, radiographic and safety outcomes of 4 years' certolizumab pegol (CZP) treatment in patients with psoriatic arthritis (PsA). Methods RAPID-PsA (NCT01087788) was double-blind and placebo-controlled to Week 24, dose-blind to Week 48 and open-label (OL) to Week 216. Patients were randomised 1:1:1 to either placebo or CZP 200 mg every 2 weeks (Q2W) or 400 mg every 4 weeks (Q4W) (following 400 mg at Weeks 0/2/4). Patients randomised to CZP continued their assigned dose in the OL period. Patients randomised to placebo were re-randomised to CZP 200 mg Q2W or 400 mg Q4W (post-loading dose) at Week 16 (early escape) or after the double-blind phase. We present observed and imputed data; missing values were imputed using non-responder imputation (NRI) for categorical and last observation carried forward (LOCF) for continuous measures. Results 409 patients were randomised; 20% (54/273) of Week 0 patients randomised to CZP had prior anti-tumour necrosis factor (TNF) exposure; 67% (183/273) completed 216 weeks. By Week 48, 60.4% of patients achieved Disease Activity Index for Psoriatic Arthritis low disease activity or remission, which was maintained; 66.3% achieved these outcomes at Week 216 (NRI). At Weeks 48 and 216, 39.2% of patients achieved minimal disease activity (NRI). 75% reduction in Psoriasis Area and Severity Index responses were 65% and 52% at Weeks 48 and 216 (NRI). Total resolution rates for enthesitis, dactylitis and nail psoriasis, at 4 years, were 71%, 81% and 65%, respectively (LOCF). Structural damage progression was low over 4 years' treatment. No new safety signals were identified after Week 96. Conclusions CZP efficacy in treating PsA was maintained over 4 years, in patients both with and without prior anti-TNF exposure, with no new safety signals identified.
Background: Psoriatic Arthritis Disease Activity Score (PASDAS),1Disease Activity Index for Psoriatic Arthritis (DAPSA),2 and the minimal disease activity (MDA) criteria3 are instruments recommended for evaluating disease activity (DA) in psoriatic arthritis (PsA). RAPID-PsA demonstrated the sustained efficacy of certolizumab pegol (CZP) across the spectrum of PsA symptoms.4 A substantial proportion of patients (pts) completing 4 years' treatment achieved DA targets; ~75% reached DAPSA low DA (LDA) or remission (REM), and almost 60% had MDA (≥5/7 MDA criteria), half of whom also achieved very low DA (VLDA) (7/7 MDA criteria).5 Objectives: To report the proportion of pts who achieved PASDAS VLDA and LDA over 216 weeks' (wks') CZP treatment, and the overlap in pts achieving PASDAS, DAPSA and MDA. Methods: RAPID-PsA (NCT01087788) was double-blind and placebo-controlled to Wk24, dose-blind to Wk48, and open-label (OL) to Wk216.5 Outcomes reported for pts randomised to CZP at Wk0 (200 mg every 2 wks or 400 mg every 4 wks, following a 400 mg loading dose at Wks0/2/4) are PASDAS change from baseline (CFB); pts achieving PASDAS LDA (>1.9-<3.2), PASDAS VLDA (≤1.9), DAPSA LDA (>4-≤14), DAPSA REM (≤4), MDA and VLDA to Wk216; and the overlap in pts achieving PASDAS VLDA, DAPSA REM, and VLDA, at Wk216. Data are summarized for observed cases per visit. Pts withdrawing between scheduled visits had their final assessment values assigned to the next scheduled visit timepoint. Results: Of 409 pts randomised, 273 received CZP from Wk0, of whom 248 (90.8%) completed Wk24 and 183 (67.0%) completed Wk216. The mean (SD) baseline PASDAS was 6.0 (1.0): In the high DA range, CFB at Wk216 was-3.4 (1.5). Of pts completing Wk216, 66.3% (118/178) were in PASDAS LDA or VLDA (PASDAS VLDA: 36.5% [n=65]): Less than the proportion reaching DAPSA LDA or REM (76.2%), but more than those achieving MDA or VLDA (57.8%) (Figure A). At Wk216, of pts achieving PASDAS VLDA, a large proportion (71% [46/65]) had VLDA based on MDA criteria (Figure B1) and most (94% [61/65]) achieved DAPSA REM (Figure B2). Almost all pts achieving VLDA (96.1% [50/52]) were also in DAPSA REM (Figure B3). After 4 years' CZP treatment, 25.8% (46/178) pts achieved the PASDAS VLDA, DAPSA REM and VLDA. Conclusion: A substantial proportion of pts completing 4 years' CZP treatment achieved PASDAS LDA or VLDA, and the vast majority who achieved PASDAS VLDA at Wk216 also reached DAPSA REM and/or VLDA. 1 in 4 pts achieved the most stringent DA target with all 3 instruments.
Objectives: To evaluate the association between improvements in clinical outcomes and burden on work productivity in psoriatic arthritis (PsA) patients during long-term treatment with certolizumab pegol (CZP). Methods: Analyses used data from patients originally randomised to CZP in RAPID-PsA (NCT01087788), a 216-week phase 3 study.1 Responders and non-responders of American College of Rheumatology (ACR) 20/50/70 criteria were compared in terms of paid work and household productivity, assessed with the arthritis-specific Work Productivity Survey. An inverse probability weight model was used to account for predictors of dropout over 216 weeks. Cumulative days missed since study baseline were estimated using a weighted generalised estimating equations model. Results: 273 patients were randomised to CZP, 183 (67.0%) of whom completed Week 216. At baseline, 60.8% of patients were employed outside the home. Through Week 216, fewer paid work days missed due to arthritis (absenteeism) were associated with stringent disease activity thresholds: non-response, 35.7 (95% confidence interval, 17.9–53.5); ACR20 to <50, 20.9 (9.2–32.6); ACR50 to <70, 7.7 (3.2–12.1); ACR70, 4.1 (0.4–7.9). Stringent levels of disease control were also associated with fewer days of reduced workplace productivity (presenteeism): non-response, 141.2 (64.0–218.3); ACR20 to <50, 71.2 (32.4–110.0); ACR50 to <70, 19.3 (11.3–27.3); ACR70, 5.6 (2.0–9.2). Patients achieving stringent ACR thresholds also reported fewer days of household work absenteeism: non-response, 189.9 (129.1–250.7); ACR20 to <50, 124.0 (80.0–168.1); ACR50 to <70, 71.6 (16.5–126.8); ACR70, 8.5 (4.4–12.5), and presenteeism: non-response, 244.1 (177.4–310.7); ACR20 to <50, 144.5 (109.0–180.0); ACR50 to <70, 105.8 (56.3–155.2); ACR70, 20.3 (6.5–34.0). Conclusions: Over four years of CZP treatment, achievement of increasingly stringent thresholds of disease control in patients with PsA was associated with decreased burden on paid and household work productivity. 1. van der Heijde D. et al. RMD Open 2018;4:e000582.
Background: Several disease activity measures and thresholds have been recommended as psoriatic arthritis (PsA) treatment targets, although consensus on the most appropriate assessment tool is lacking.1 Reports suggest low disease activity (LDA) and remission may be associated with minimal structural progression in PsA.2 Objectives: To report the relationship between PsA disease activity and structural progression over 216 weeks' (wks) treatment with certolizumab pegol (CZP), an Fc-free, PEGylated, tumour necrosis factor inhibitor (TNFi) that has shown long-term efficacy and safety in PsA.3 Methods: Patients (pts) enrolled in RAPID-PsA (NCT01087788) with active PsA (≥3 tender joints; ≥3 swollen joints; ESR ≥28 mm/hour and/or CRP >upper limit of normal) who had failed treatment with ≥1 csDMARD were randomised 1:1:1 to CZP 200 mg every 2 wks (Q2W), CZP 400 mg every 4 wks (Q4W), or placebo (PBO). All CZP pts received CZP 400 mg at Wks 0/2/4. PBO pts were re-randomised to CZP 200 mg Q2W or 400 mg Q4W at Wk 16 or 24.3 Pts were heterogenous for structural damage and disease duration at baseline. Disease activity was assessed using minimal disease activity (MDA) criteria (MDA: 5-6/7 criteria; very LDA [VLDA]: 7/7 criteria), Psoriatic Arthritis Disease Activity Score (PASDAS) (LDA: >1.9-≤3.2; remission: ≤1.9), or Disease Activity Index for Psoriatic Arthritis (DAPSA) (LDA: >4-≤14; remission: ≤4). Radiographs were read in four reading campaigns using the van der Heijde modified Total Sharp Score (mTSS) for PsA. A risk of structural progression (RSP) subgroup (baseline mTSS >median for all pts) was also assessed. Mean change from baseline (CFB) in mTSS and associations with disease activity states were estimated using a hierarchical linear mixed effects model (fixed effects: reading campaign/interactions of concurrent disease activity levels with time; random effects: pt/reading campaign nested within pt) which allowed mean mTSS trajectory, and impact of disease activity levels on this, to differ over time. Results: 407/409 randomised pts were assessed for mTSS at least once. At Wk 0, mean (standard deviation) DAPSA=44.5 (22.7), PASDAS=6.0 (1.1). 3/409 (0.7%) pts reported MDA. The proportion of pts achieving remission/VLDA states increased to Wk 216, as did estimated mean mTSS. Estimated mean mTSS CFB remained low overall (0.46 at Wk 216; standard error 0.16; Figure). Across disease activity measures, remission/VLDA states were associated with mTSS estimated mean CFB ≤0 in both the overall group and RSP subgroup (Table). Conclusion: These data indicate that achievement of remission in PsA is important to prevent further structural damage, particularly in pts with pre-existing structural changes. This supports the rationale for strict disease activity targets.
Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy and safety of Certolizumab Pegol (CZP) in subjects with adult onset active and progressive Psoriatic Arthritis (PsA).
