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1 1 EULAR 213

2 2 CZP in AxSpA

3 Effects of certolizumab pegol (CZP) on the signs and symptoms of AxSpA at week 24 (RAPID-AxSpA) 3 RAPID-AxSpA: Ongoing 24-week trial in adult patients with active AxSpA according to ASAS criteria, including AS (mny positive) and nr-axspa (mny negative) populations Double-blind and placebo (PBO)-controlled through week 24, dose-blind through week 48, with an open-label extension (OLE) through week 158 Double-blind, PBO-controlled Active AxSpA patients BASDAI 4 Back pain 4* CRP > ULN or MRI evidence of sacroiliitis N=325 n=111 n=17 n=17 1:1:1 Randomization Loading dose (LD): CZP 4 mg (Wk, 2, 4) LD: CZP 4 mg (Wk, 2, 4) PBO CZP 2 mg Q2W CZP 4 mg Q4W PBO PBO escape Wk 16 CZP 2 mg Q2W CZP 4 mg Q4W Week LD for both: CZP 4 mg (Wk 16, 18, 2) 24 Primary clinical endpoint: ASAS2 AS, ankylosing spondylitis; ASAS, Assessment of SpondyloArthritis; AxSpA, axial spondyloarthritis; mny, modified New York; nr-axspa, nonradiographic axial spondyloarthritis * to 1 numeric rating scale (NRS; from BASDAI item 2); ULN, upper limit of normal, ULN=7.9 mg/l; Within the last 3 months from screening, as defined by ASAS criteria; Patients who failed to achieve an ASAS2 response at both week 14 and week 16 were randomized at week 16 to receive CZP 2 mg Q2W or CZP 4 mg Q4W following loading dose Landewé et al. Arthritis Rheum. 212;64:S336 van der Heijde et al. Arthritis Rheum. 212;64:S73

4 Effects of certolizumab pegol (CZP) on the signs and symptoms of AxSpA at week 24 (RAPID-AxSpA) 4 Primary endpoint: A week 12 ASAS2 response was achieved in significantly more patients receiving CZP 2 mg Q2W and CZP 4 mg Q4W compared with patients receiving placebo (PBO) (57.7% and 63.6% vs 38.3%, respectively; P.4) Significant improvements in ASAS2 were observed as early as week 1 (4.5% and 34.6% in the CZP 2 mg and 4 mg arms, respectively, vs 14.% in the PBO arm; P<.1) and were maintained at week 24 Week 24 response and remission rates (NRI) ASAS4 ASAS partial remission 1 Patients (%) * * * * * * * * * AxSpA AS nr-axspa AxSpA AS nr-axspa n= PBO CZP 2 mg Q2W CZP 4 mg Q4W AS, ankylosing spondylitis; ASAS, Assessment of SpondyloArthritis; AxSpA, axial spondyloarthritis; nr-axspa, nonradiographic axial spondyloarthritis * P.1; P<.5 Landewé et al. EULAR 213; Oral OP16

5 Effects of certolizumab pegol (CZP) on the signs and symptoms of AxSpA at week 24 (RAPID-AxSpA) 5 AxSpA patients (pts)* showed statistically significant improvements in key secondary endpoints when treated with CZP, compared with pts who received placebo (PBO) Similar improvements were reported with CZP vs PBO in both AS (mny positive) and nr-axspa (mny negative) subpopulations Week 24 change from baseline in AxSpA pts (LOCF) Mean Δ from baseline BASDAI P< BASFI P< PBO (n=17) BASMI -.5 P<.1 CZP (combined doses, n=218) Adverse events (AEs) occurred in 7.4% vs 62.6%, serious AEs in 4.7% vs 4.7%, and serious infections in 1.1% vs % of CZP (combined dose) pts vs PBO pts No deaths or malignancies were reported Authors conclusion: Both CZP doses rapidly improved symptoms of AxSpA, with similar improvements observed in AS and nr-axspa subpopulations, and with no new observed safety signals AS, ankylosing spondylitis; AxSpA, axial spondyloarthritis; BASDAI; Bath Ankylosing Spondylitis Disease Activity Index; BASFI; Bath Ankylosing Spondylitis Functional Index; BASMI; Bath Ankylosing Spondylitis Metrology Index; mny, modified New York; nr-axspa, nonradiographic axial spondyloarthritis; * By ASAS criteria; CZP 2 mg Q2W or CZP 4 mg Q4W following loading dose Landewé et al. EULAR 213; Oral OP16

6 Effects of certolizumab pegol (CZP) on patient-reported outcomes in AxSpA (RAPID-AxSpA) 6 Mean Δ from baseline Patient-reported outcomes (PROs) from patients enrolled in the ongoing placebo (PBO)-controlled RAPID-AxSpA trial and open-label extension were evaluated following 24 weeks of CZP treatment Mean change from baseline in PROs at week 24 in AxSpA patients (LOCF) Total back pain (NRS) Fatigue (NRS) AxSpA AS nr-axspa AxSpA AS nr-axspa AxSpA AS nr-axspa * * * * * * * * * -5 * * * * * * * * * n= PBO CZP 2 mg Q2W CZP 4 mg Q4W Patients treated with CZP also had significant improvements in MOS-SPI, SF-36 PCS and MCS components, and AsQoL compared with patients receiving PBO Similar improvements in PROs were observed in both AS and nr-axspa subpopulations Relative to PBO patients, CZP-treated nr-axspa patients demonstrated a greater improvement in BASFI and sleep compared to AS patients, and were more likely to reach population norms for SF-36 Authors conclusions: Both CZP dosing schedules rapidly improved all PROs, including pain, fatigue, physical function, and HRQoL of AxSpA, in both AS and nr-axspa patients BASFI AsQoL, ankylosing spondylitis quality of life; BASFI, Bath Ankylosing Spondylitis Functional Index; LOCF, last observation carried forward; MCS, Mental Component Summary; MOS-SPI, Medical Outcome Study Sleep Problem Index; NRS, numeric rating scale; PCS, Physical Component Summary; SF-36, 36-Item Short-Form Health Survey; *P<.5 vs PBO Sieper et al. EULAR 213; Poster THU36

7 Mean days (per month) Effects of certolizumab pegol (CZP) on productivity in AxSpA patients (RAPID-AxSpA) Patients enrolled in the ongoing, placebo-controlled RAPID-AxSpA trial* and open-label extension were evaluated for work and home productivity following 24 weeks of treatment with CZP Work Social participation days missed at week 24 (LOCF) PBO CZP 2 mg Q2W CZP 4 mg Q4W Household Social AxSpA AS nr-axspa n = Authors conclusions In the overall AxSpA population, CZP improved workplace productivity in employed patients by reducing absenteeism, presenteeism, and AxSpA interference with work CZP also improved household productivity and increased participation in social and daily activities Similar improvements were observed in AS and nr-axspa populations Work Household Social Work Household Social 7 AS, ankylosing spondylitis; AxSpA, axial spondyloarthritis; LOCF, last observation carried forward; nr-axspa, nonradiographic axial spondyloarthritis * Included mny positive (AS) and ASAS positive/mny negative (nr-axspa) patients with objective signs of active disease (BASDAI 4, Back Pain NRS 4, CRP > ULN or MRI evidence of sacroiliitis); Arthritis-specific Work Productivity Survey (WPS) was administered Q4W; Employed subjects only; P.5 vs PBO van der Heijde et al. EULAR 213; Oral OP17

8 8 CZP in PsA

9 Effects of certolizumab pegol (CZP) on the signs and symptoms of PsA at Week 24 (RAPID-PsA) 9 RAPID-PsA: Ongoing 158-week trial in adult patients with active PsA Double-blind and PBO-controlled through week 24, dose-blind through week 48, with an open-label extension (OLE) through week 158 Enrolled patients included those who experienced secondary failure to 1 previous anti-tnf agent Double-blind, placebo-controlled Active PsA patients PsA 6 mo by CASPAR Skin lesion >3 TJC/SJC CRP or ESR > ULN Failed 1 previous DMARD N=49 n=138 n=135 n=136 Loading dose (LD): CZP 4 mg (Wk, 2, 4) LD: CZP 4 mg (Wk, 2, 4) PBO CZP 2 mg Q2W CZP 4 mg Q4W Placebo Placebo escape Week 16 CZP 2 mg Q2W CZP 4 mg Q4W Week LD for both: CZP 4 mg (Wk 16, 18, 2) 24 Randomization 1:1:1 Primary clinical endpoint ACR2 Primary radiographic endpoint Δ mtss Authors conclusion: Both CZP doses improved symptoms of PsA compared with placebo, with no new observed safety signals CASPAR, Classification Criteria for Psoriatic Arthritis; DMARD, diseasemodifying antirheumatic drug; mtss, modified total Sharp score; PsA, psoriatic arthritis; SJC, swollen joint count; TJC, tender joint count Mease et al. Arthritis Rheum. 212;64:S117 Gladman et al. Arthritis Rheum. 212;64:S242 van der Heijde et al. EULAR 213; SAT281

10 Impact of prior anti-tnf therapy and skin lesions on the effectiveness of treating PsA patients with CZP (RAPID-PsA) The efficacy and safety of certolizumab pegol (CZP) was assessed in adult patients with active psoriatic arthritis (PsA) in RAPID-PsA Through week 24, patients (N=49) were randomized to either placebo (PBO) or 1 of 2 CZP doses * 1 Week 24 ACR2 response by prior anti-tnf use (NRI) Post hoc analyses of PASI response by baseline (BL) PASI score (NRI) 1 Patients (%) Prior anti-tnf Anti-TNF naïve 1 Patients (%) Week PASI PBO CZP 2 mg Q2W CZP 4 mg Q4W Serious adverse events occurred in 7% of combined CZP-treated patients vs 4% in PBO Authors conclusion: Both CZP doses rapidly improved symptoms of PsA compared with placebo, with no new observed safety signals Patients with higher BL PASI were more likely to achieve a PASI75 and a PASI9 response Similar ACR response rates with CZP were observed in pts with and without prior anti-tnf exposure *CZP 4 mg at wk, 2, and 4 (loading dose) followed by either CZP 2 mg Q2W or CZP 4 mg Q4W SC P<.1 vs PBO Statistics not reported for the post hoc analyses PASI9 BL PASI <1 1 <1 1 n= n= Mease et al. EULAR 213; Poster SAT298

11 Effects of certolizumab pegol (CZP) on patient-reported outcomes in active PsA (RAPID-PsA) Patient-reported outcomes (PROs) were assessed in adult patients with active psoriatic arthritis (PsA) in the ongoing RAPID-PsA study Through week 24, patients (N=49) were randomized to either placebo (PBO) or 1 of 2 CZP doses * 11 Baseline (BL) and mean change from baseline (CFB) in PROs at week 24 in PsA patients (LOCF) PBO (n=136) CZP 2 mg Q2W (n=138) CZP 4 mg Q4W (n=135) PRO BL Wk 24 CFB BL Wk 24 CFB BL Wk 24 CFB FAS Pain (VAS) HAQ DI SF-36 (PCS) SF-36 (MCS) PsAQoL DLQI In post hoc analyses, similar levels of PRO improvement were observed in patients with and without prior anti-tnf exposure Authors conclusions: Both CZP dosing schedules improved multiple PROs in patients with PsA, relative to patients receiving PBO DLQI, Dermatology Life Quality Index; FAS, Fatigue Assessment Scale; MCS, Mental Component Summary; PCS, Physical Component Summary; PsAQoL, PsA quality of life; SF-36, 36-Item Short-Form Health Survey; VAS, visual analog scale * CZP 4 mg at wk, 2, and 4 (loading dose) followed by either CZP 2 mg Q2W or CZP 4 mg Q4W SC P<.5 vs PBO Gladman et al. EULAR 213; Poster SAT26

12 Effects of certolizumab pegol (CZP) on social participation in PsA patients (RAPID-PsA) 12 Changes in home/work productivity in response to treatment with CZP was evaluated in adult patients with active psoriatic arthritis (PsA) in the ongoing RAPID-PsA study Through week 24, patients (N=49) were randomized to either placebo (PBO) or 1 of 2 CZP doses * Days missed/month, mean 5 Work and social days missed in PsA patients treated with CZP for 24 weeks (LOCF) PBO 4.7 CZP 2 mg Q2W CZP 4 mg Q4W n=77 n=83 n=83 n=136 n=138 n=135 n=136 n=138 n=135 Work days missed Patients receiving CZP also had a reduced number days/month in which productivity at work or in the home was reduced by 5% due to arthritis symptoms, compared with patients receiving PBO Authors conclusions CZP significantly improved workplace productivity in employed patients with PsA by reducing absenteeism and presenteeism, compared with patients receiving PBO PsA patients receiving CZP also experienced improved household productivity and increased participation in social and leisure activities relative to PBO LOCF, last observation carried forward Arthritis-specific Work Productivity Survey (WPS) was administered Q4W * CZP 4 mg at wk, 2, and 4 (loading dose) followed by either CZP 2 mg Q2W or CZP 4 mg Q4W SC; Employed subjects only; P.5 vs PBO Household work days missed Family/social/lesiure days missed Kavanaugh et al. EULAR 213; Poster SAT276

13 13 Impact of imputation methodology on reported radiographic progression outcomes in PsA patients (RAPID-PsA) Radiographic progression was evaluated in patients with active psoriatic arthritis (PsA) enrolled in the 24-week, placebo (PBO)-controlled portion of the ongoing RAPID-PsA study Patients (N=49) were randomized to either placebo (PBO) or 1 of 2 certolizumab pegol (CZP) doses * Imputation in pts with <2 X-rays available PBO (n=136) LS mean mtss CFB at Wk 24 (SE) % of Non-progressors at Wk 24 CZP 2 mg Q2W (n=138) CZP 4 mg Q4W (n=135) CZP combined (n=273) PBO (n=136) CZP 2 mg Q2W (n=138) CZP 4 mg Q4W (n=135) CZP combined (n=273) Prespecified imputation methodology (7.73) (7.59) 25.5 (7.92) (6.7) No imputation.29 (.8).1 (.8).12 (.8).6 (.6) Median mtss CFB of all pts observed.28 (.7).1 (.7).11 (.8).6 (.6) Mean mtss CFB of all pts observed.28 (.7).1 (.7).11 (.8).6 (.6) Maximum mtss CFB of all pts observed.66 (.13).18 (.13).52 (.13).35 (.1) Maximum mtss CFB by treatment group.39 (.11).14 (.11).49 (.12).31 (.9) The prespecified imputation analysis overestimated radiographic progression in all arms Conventional post hoc analyses suggested that CZP inhibited radiographic progression compared to PBO Patients with mtss 6 (median score) or CRP 15 mg/l at BL showed little radiographic progression in both the CZP and PBO groups Higher BL mtss and elevated CRP were also associated with a higher rate of non-progression in CZP vs PBO groups Authors conclusions: Conventional imputation methods showed that CZP inhibited radiographic progression in PsA patients, particularly in those with a higher risk of progression mtss, modified total Sharp score * CZP 4 mg at wk, 2, and 4 (loading dose) followed by either CZP 2 mg Q2W or CZP 4 mg Q4W SC; P<.5 vs PBO van der Heijde et al. EULAR 213; Poster SAT281

14 14 CZP in RA

15 Safety and efficacy of certolizumab pegol (CZP) + MTX after 5 years of treatment in RA patients (RAPID-OLE) 15 Eligible RA patients were enrolled in the open-label extension (OLE) to the RAPID 1 study to assess the safety and efficacy of CZP plus MTX over 5 years in RA In this OLE to the RAPID 1 study, patients were initially treated with MTX plus CZP 4 mg Q2W,* with the CZP dose decreased to 2 mg Q2W after 6 months CZP 4 mg Q2W* + MTX RAPID 1 CZP 2 mg Q2W + MTX PBO + MTX RAPID 1 (OLE) CZP 4 mg Q2W* + MTX for 6 months then CZP 2 mg Q2W + MTX Randomization Patient retention and efficacy data Safety data Week (4.9 years) 334 (6.4 years) * CZP 4 mg every 2 weeks is not an approved maintenance dose. For maintenance, the approved dose of CZP is 2 mg every other week, or alternatively, 4 mg every 4 weeks may be considered Keystone et al. EULAR 213; Abstract THU192

16 Safety and efficacy of certolizumab pegol (CZP) + MTX after 5 years of treatment in RA patients (RAPID-OLE) 16 Retention rate (%) Kaplan-Meier estimator Selected efficacy data to week CZP completers (n=57) Patient retention to week 256 (ITT, N=783) % 73.4% 72.6% 61.2% Week from first dose of CZP ITT population (n=783) ACR2/5/7 response rate 74.6%/57.4%/39.6% 59.%/43.7%/28.8% DAS28(ESR) remission rate 25.2% 2.3% 68.7% 55.3% Withdrawal due to AEs or lack of efficacy Withdrawal due to any reason Patient censored Authors conclusions: CZP plus MTX provided a favorable riskbenefit profile over 5 years of treatment in RA patients Safety data to week (safety population, N=846) Event rate per 1 pt-years Any AE Urinary tract infection 7.8 Nasopharyngitis 7.4 Upper RT infection 7.3 Any serious AE 18.4 Serious infection 5.4 Serious malignancy 1. Incidence rate per 1 pt-years AEs leading to withdrawal 3.77 AEs leading to death.44 Tuberculosis 2.6 Number of patients Deaths 16 Malignancies 4 Infections 3 Cardiovascular events 2 CZP 4 mg Q2W, reduced to 2 mg Q2W after 6 months. Missing categorical data were imputed by nonresponder imputation (NRI) and missing continuous measures were imputed by last observation carried forward (LOCF) 1. Keystone et al. EULAR 213; Abstract THU Keystone et al. EULAR 213; Poster THU192

17 FcRn binding and FcRn-mediated transcytosis of anti-tnf agents 17 In vitro quantification of anti-tnf binding affinities for human neonatal Fc receptor (hfcrn) and FcRn-mediated transcytosis Binding affinity of anti-tnf agents for hfcrn Anti-TNF K d Transcytosis of anti-tnfs across hfcrn-expressing epithelial cells 3 IFX ADA ETA CZP Non-PEGylated CZP Fab 132 nm 225 nm 15 nm ND ND ng/ml (Mean ± SD over 4 h) Average = P146* CZP ADA IFX ETA 5.9 ng/ml 3.2 ng/ml ng/ml ng/ml 81.3 ng/ml Authors conclusions ADA, IFX, and ETA demonstrated binding affinity to hfcrn, and were actively transported across an hfcrn-expressing epithelial monolayer CZP and the non-pegylated CZP Fab fragment did not demonstrate detectable binding to hfcrn ADA, adalimumab; CZP, certolizumab pegol; ETA, etanercept; Fab; fragment antigen binding; Fc, fragment, crystallizable; Kd, dissociation constant; IFX, infliximab; ND, not detected; PEG, polyethylene glycol * Non-FcRn-binding control antibody Baker et al. EULAR 213; Poster FRI162

18 The effect of enforcing TB screening rules in the clinical trials of certolizumab pegol (CZP) 18 The safety database for clinical trials of CZP in rheumatoid arthritis (RA) patients was reviewed through Nov. 211 to determine the effect of introducing more stringent tuberculosis (TB) screening protocols (according to WHO guidelines) CZP trials were assessed as 2 groups: trials initiated before the 27 protocol amendment (early trials) and trials initiated after the protocol amendment (recent trials) Early trials 27 Retrospective * protocol amendment (recent trials) TB cases in CZP clinical trials n IR/1 PY Patients included if PPD negative according to national guidelines (PPD positivity: <5-2 mm) PPD cutoff: <5 mm Patients with PPD 5 mm treated with INH + 6-month questionnaire All patients in ongoing trials with PPD 5 mm treated with isonicotinylhydrazine (INH) CZP safety database Confirmed TB cases Eastern Europe Central Europe Western Europe North America TB in early trials TB in recent trials 2.18 Of the 44 confirmed TB cases, 11 cases were diagnosed after 28, when the protocol amendment was enforced Authors conclusions: Following implementation of the WHO recommendations for PPD cutoff, the TB rate in CZP trials was similar to that seen with other anti-tnfs IR, incidence rate; PPD, purified protein derivation; PY, patient-years; WHO, World Health Organization; * All patients in ongoing trials with a baseline PPD 5 mm were treated with INH regardless of duration/exposure to CZP treatment ; Symptoms/risk factors questionnaire; Recent CZP trials recruited fewer patients from Eastern and Central Europe compared to earlier trials, which may limit comparison Vencovský et al. EULAR 213; Abstract THU24

19 Interim analysis of the effectiveness of CZP in RA patients in a noninterventional study (FasT CAN) 19 Canadian RA patients (N=15) were enrolled in an open-label, observational, noninterventional study of certolizumab pegol (CZP); interim results to Jan. 212 are presented here Mean days (per month) 8 Effects of CZP on work productivity (WPS-RA) Baseline (n=42) Work days lost Work days with productivity reduced by 5% due to arthritis Week 2/24 (n=32) DAS28 <2.6, % (n/n) DAS28 3.2, % (n/n) CDAI, mean (SD, n) Efficacy of CZP in RA patients (FAS, n=113) DAS28, mean (SD, n) HAQ DI, mean (SD, n) Baseline Week 12 Week 2/ (2/113) 33.1 (12.1, 113) 5.3 (1.1, 113) 1.5 (.6, 113) 11.6 (11/95) 32.6 (31/95) 18.1 (12.4, 11) 4. (1.3, 95) 1.1 (.7, 18) 29.5 (23/78) 47.4 (37/78) 15.8 (14.1, 9) 3.6 (1.5, 78) 1. (.8, 9) Average gains in household productivity of 1.5- to 3.1-fold were also reported at wk 2/24 Of all 15 patients, 3.7% reported adverse events (AEs), and 1.3% reported serious AEs, including serious infections (.7%). There were no deaths Authors conclusions: In daily practice in Canada, CZP-treated RA patients achieved improvements in DAS28 remission, physical function, and workplace and household productivity CDAI, Clinical Disease Activity Index; DAS28, Disease Activity Score including 28-joint count; FAS, full analysis set; HAQ DI, Health Assessment Questionnaire Disability Index; RA, rheumatoid arthritis; WPS-RA, rheumatoid arthritis-specific Work Productivity Survey Shaikh et al. EULAR 213; Abstract AB288

20 Immunogenicity of certolizumab pegol and consequences on clinical response in RA patients (HIKARI post hoc) Anti-CZP Ab titer (U/mL) Post hoc analysis of patients* enrolled in the HIKARI trial and its open-label extension, assessing the relationship between clinical response and development of antibodies (Ab) against certolizumab pegol (CZP) ACR2/5/7 responses at weeks 24 and 52 Development of anti-czp Ab Early development (n=7) Late development (n=11) Week ACR response, % All (n=116) Early Ab (n=7) Late Ab (n=11) All (n=116) Early Ab (n=7) Week 24 Week Late Ab (n=11) ACR2 ACR5 ACR7 2 Anti-CZP Ab developed in 15.5% of patients through week 24, in 1 of 2 profiles Ab development peaked between weeks 8-12 ( early development, n=7) Ab development peaked at/after week 24 ( late development, n=11) Authors conclusions: These results suggest that early, transient development of anti-czp Ab was not associated with poor long-term clinical response, whereas later development led to loss of response ACR, American College of Rheumatology; RA, rheumatoid arthritis * Received CZP 2 mg Q2W without concomitant MTX in the double-blind portion of HIKARI (n=116) Takeuchi et al. EULAR 213; Abstract FRI21

21 The effect of certolizumab pegol (CZP) on long-term control of RA symptoms in a Japanese cohort (J-RAPID and HIKARI) The efficacy of CZP* in RA patients (pts) was examined over 8 weeks of the J-RAPID and HIKARI studies and their open-label extensions (OLEs) 21 ACR response, % 1 J-RAPID study (with MTX) (n=63) ACR2 ACR5 ACR Week ACR response, % 1 HIKARI study (without MTX) (n=81) ACR2 ACR5 ACR Week J-RAPID (n=63) HIKARI (n=81) HIKARI (n=34) monotherapy In J-RAPID and HIKARI DB phases, 75.8% (269/355) of CZP and 62.8% (12/191) of PBO pts reported adverse events; incidence rates in the OLEs were similar to those in the DB phases Authors conclusions: CZP provided long-term clinical, functional, and radiographic benefits regardless of concomitant MTX or other DMARDs in a Japanese RA cohort ACR, American College of Rheumatology; DB, double-blind; HAQ, Health Assessment Questionnaire; mtss, modified total Sharp score; MTX, methotrexate; RA, rheumatoid arthritis; * CZP 2 mg Q2W or CZP 4 mg Q4W HIKARI (n=47) + non-mtx DMARDs DAS28(ESR) remission, % (week 8) mtss, Δ wk HAQ, Δ wk Tanaka et al. EULAR 213; Abstract AB294

22 Predictability of long-term outcomes in RA patients responding to treatment with certolizumab pegol The ability to predict long-term outcomes of treatment with certolizumab pegol (CZP, 2 mg Q2W) in RA patients was examined in the context of week 12 response (R) or nonresponse (NR) * in a Japanese cohort (J-RAPID and HIKARI trials) Predictability of week 52 clinical outcomes based on week 12 response to CZP 22 Subgroup Wk 52 remission in wk 12 R Wk 52 remission in wk 12 NR Negative predictive value OR (95% CI) Δ mtss, mean in wk 12 R Δ mtss, mean in wk12 NR J-RAPID (n=82) 41.3% 5.3% ( ) HIKARI All (n=116) 34.9% 6.7% ( ) HIKARI Non-MTX DMARD (n=62) 39.2% % 1. Not calculated HIKARI Monotherapy (n=54) 28.6% 1.5% ( ) Authors conclusions: These analyses suggest that DAS28 response at wk12 predicts long-term clinical and structural outcomes regardless of concomitant medication or BL disease status in Japanese patients treated with CZP CI, confidence interval; DAS28, Disease Activity Score including 28-joint count; mtss, modified total Sharp score; MTX, methotrexate; OR, odds ratio; RA, rheumatoid arthritis; * R, DAS28 change 1.2 at week 12; NR, DAS28 change <1.2 at week 12 ; DAS28 <2.6 at week 52 Yamanaka et al. EULAR 213; Abstract THU199

23 Analysis of comorbidities and medical management of RA patients in a French claims database 23 RA patients were identified from the EGB database (N~38,), a representative sample of individuals covered by the French Public Sickness Fund, and were compared to a matched control group Patients receiving biologics* (n=214) 4.2%.5%.5% Etanercept 9.8% Adalimumab Infliximab Frequencies of comorbidities among RA patients Patients (%) Control (n=3888) RA (n=1296) Patients with comorbidities 1625 (41.8) 511 (39.4) Alzheimer s disease 5 (3.1) 7 (1.4) Asthma 16 (1.) 13 (2.5) Hypertension (severe) 259 (15.9) 11 (19.8) Ischemic heart disease 98 (6.) 39 (7.6) 12.6% 51.3% Rituximab Abatacept Atherosclerosis 65 (4.) 15 (2.9) Heart failure 44 (2.7) 12 (2.3) Angina pectoris 44 (2.7) 11 (2.2) 2.1% Tocilizumab Anakinra Malignancies 144 (8.9) 44 (8.6) Non-insulin-dependent diabetes mellitus 39 (19.) 8 (15.7) Insulin-dependent diabetes mellitus 35 (2.7) 14 (2.7) Depression 56 (3.4) 25 (4.9) The crude RA prevalence rate was 3.47/1 people The gender ratio was.33 (M:F) and mean age was 63.3 ± 14.8 years, with a time since admission to full coverage for RA of 8.8 ± 7.2 years (<2 years in 23.8% of patients) Authors conclusions Anti-TNF adherence in this cohort is similar to results observed in other registries Observed differences in the comorbidity profile of RA patients should be analyzed further * Doses received were not specified; P<.5; P<.1 Fautrel et al. EULAR 213; Abstract THU512

24 Cost-effectiveness of certolizumab pegol (CZP) in an outcomes-based risk-sharing scheme in Finland 24 A risk-sharing scheme (RSS) for CZP was evaluated for treatment response and per-patient value in a Finnish population Cost-effectiveness and per-population budget impacts were assessed over a 5-year horizon RSS for CZP in RA Responder Continue CZP Week 12 ACR2 response Nonresponder CZP acquisition costs refunded and alternate therapy initiated Estimated ACR response at week 12 Patients, % CZP 72.4% (95% CI: 64.7% 8.3%) Adalimumab 6.2% Etanercept 52.5% Golimumab 55.5% Over 5 years, introducing the CZP RSS for all new patients provided cost savings per patient of 4,796 together with.4 additional QALY If using an RSS, approximately 4.7% of CZP acquisition costs would be refunded The corresponding budget per patient-year was estimated at 27,31, which could potentially be reduced to an average of 26,178 if all starting patients received CZP under an RSS Authors conclusions: CZP was shown to be effective and cost effective compared to the current mix of treatments in Finland, with an outcomes-based RSS increasing affordability even further Asseburg et al. EULAR 213; Abstract FRI184

25 25 Epratuzumab

26 Effect of long-term treatment with epratuzumab on B-cell counts and Ig levels in patients with SLE The effect of long-term epratuzumab (Emab) treatment on B cells, T cells, and immunoglobulin (Ig) levels was evaluated in the open-label extension (OLE) study to EMBLEM TM (SL8) Results B-cell counts were moderately reduced, plateauing at approximately 5% below EMBLEM TM baseline at week 112 Ig levels remained with normal ranges BILAG score BILAG improvements B cells at EMBLEM TM OLE screening n Mean (SD) n/n % < Median (12.7) 24/ Median (12.5) 28/ P value BILAG scores and improvements at week 48 were similar regardless of total B-cell counts at the start of the study Authors conclusions: The lack of correlation between B-cell counts and week 48 clinical response suggest the MOA for Emab as B-cell modulation, not depletion BILAG, British Isles Lupus Assessment Group index; SLE, systemic lupus erythematosus 12 mg Emab infused at weeks and 2 of repeating 12-week cycles through week Strand et al. EULAR 213; Poster THU286

27 27 AxSpA (general)

28 Efficacy of etanercept in nonradiographic axial spondyloarthritis patients (AS-EARLY) 28 AS-EARLY: 12-Week randomized, double-blind, placebo-controlled study Compared etanercept (ETN) with placebo (PBO) in the treatment of nonradiographic axial spondyloarthritis (nr-axspa) patients with insufficient response to NSAIDs Clinical assessments and MRI of spine and sacroiliac joints* were performed at baseline and week 12 Inclusion criteria Met ASAS AxSpA criteria Did not meet mny criteria Symptom duration.25-5 y BASDAI 4 despite NSAID use Inadequate response to 2 NSAIDs ETN 5 mg weekly (+ background NSAID ) PBO (+ background NSAID ) Randomization Stratified by MRI evidence of sacroiliitis and geographic region Week 12 N values not specified Primary endpoint: ASAS4 mitt population ASAS, Assessment of Spondyloarthritis; AxSpA, axial spondyloarthritis; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; mny, modified New York; mitt, modified intent-to-treat * Average of 2 independent central readers according to Spondyloarthritis Research Consortium of Canada indices; Specific NSAID and dosage(s) not specified Dougados et al. EULAR 213; Oral OP18

29 Efficacy of etanercept in nonradiographic axial spondyloarthritis patients (AS-EARLY) AS-EARLY: 12-Week, placebo-controlled study in patients who met the ASAS criteria for AxSpA, but not the mny criteria for AS (N values not specified) 29 1 Patients (%) P= ASAS4 (Primary endpoint) Response rate at week 12 (mitt) NS P= ASAS 2 P= ASAS PR P< ASAS 5/6 P= BASDAI 5 Mean Δ from baseline (SE) -6 Week 12 change from baseline (mitt) ASDAS CRP P<.1 BASDAI P=.19 BASFI P=.16 SPARCC * (spine) P=.4 SPARCC (SIJ) P<.1 PBO + NSAID ETN 5 mg QW + NSAID Authors conclusion In a population of AxSpA patients (ASAS+/mNY-) with inadequate response to NSAIDs, ETN was more effective than PBO in decreasing clinical and MRI-determined measures of disease activity and function AS, ankylosing spondylitis; ASAS, Assessment of Spondyloarthritis; ASDAS, Ankylosing Spondylitis Disease Activity Score; AxSpA, axial spondyloarthritis; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; mitt, modified intent-to-treat; mny, modified New York; PR, partial remission; SIJ, sacroiliac joint; SPARCC, Spondyloarthritis Research Consortium of Canada *Range -18; Range -72 Dougados et al. EULAR 213; Oral OP18

30 Post hoc analysis of long-term efficacy and safety of ADA in patients with nr-axspa (ABILITY-1) 3 ABILITY-1: An ongoing, phase 3, randomized controlled trial (RCT) and open-label extension (OLE) study of adalimumab (ADA) in patients (N=185) * with nonradiographic AxSpA (nr-axspa) This post hoc analysis examined the safety and efficacy of ADA at week 14 in a subpopulation of MRI- or CRP-positive patients Total population (N=185) RCT OLE (Up to an additional 144 weeks) MRI/CRP+ subpopulation Positive MRI at baseline (SPARCC 2 for SIJ or spine) or Elevated CRP n=142 ADA 4 mg EOW n=69 PBO n=73 Week Primary endpoint Data used in post hoc analysis (75% available, n=17) AxSpA, axial spondyloarthritis; EOW, every other week; SPARCC, Spondyloarthritis Research Consortium of Canada * Enrolled patients had an inadequate response, intolerance, or contraindication to NSAIDs; Diagnostic criteria not specified; Threshold not specified Sieper et al. EULAR 213; Oral OP19

31 Post hoc analysis of long-term efficacy and safety of ADA in patients with nr-axspa (ABILITY-1) Post hoc analysis of the ABILITY-1 open-label extension study evaluating clinical response and sustained remission in the MRI/CRP+ subpopulation* Clinical responses of the MRI/CRP+ subpopulation (completer analysis ) 31 Patients (%) 1 ADA 4 mg EOW 82. ASAS ASAS 4 BASDAI n=17 n=17 n=17 n=15 n=14 n=11 n=12 ASDAS ID ASAS PR ASDAS ID ASAS PR Week 14 Sustained remission (Weeks 52, 8, and 14) In the PY of ADA exposure during the study, there were 8 serious infections (2.2/1 PY, including 1 case of disseminated TB), 1 case of lupus-like syndrome, and 2 deaths No malignancies or demyelinating diseases have been reported Authors conclusions Almost half of patients were in remission (ASDAS ID or ASAS PR) at week 14, and the majority of week 14 remitters were also in remission at weeks 52 and 8 Long-term safety data are comparable to other rheumatology indications ASAS, Assessment of Spondyloarthritis; ASDAS ID, Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS <1.3); ASAS PR, ASAS partial remission; AxSpA, axial spondyloarthritis; BASDAI5, Bath Ankylosing Spondylitis Disease Activity Index 5% improvement; PY, patient-years; SPARCC, Spondyloarthritis Research Consortium of Canada; * nr-axspa diagnostic criteria not specified. Enrolled patients had an inadequate response or intolerance/contraindication to NSAIDs; positive MRI (SPARCC score 2 for SIJ or spine) or elevated CRP levels (threshold not specified) at baseline; Data as observed; Suicide and cardiopulmonary failure due to opiate toxicity Sieper et al. EULAR 213; Oral OP19

32 The effect of anti-adalimumab antibodies on drug levels and clinical response in ankylosing spondylitis patients The relationship between antibodies-to-adalimumab (ATA), adalimumab (ADA) concentrations, and clinical response/disease activity in ankylosing spondylitis (AS) patients (N=115) was evaluated in a retrospective cohort study for up to 24 weeks of follow-up ADA levels in AS patients with and without detectable ATA at Week 24 Median ADA concentration (mg/l) 14 P< Week Increased ADA levels were significantly associated with ASDAS reductions (P=.2; RC=-1.1; 95% CI: -2. to -.2) No significant association with BASDAI responses was observed Authors conclusions: ATA correlate with ADA levels and clinical response, suggesting that therapeutic drug monitoring may be a useful tool in treatment optimization CI, confidence interval; RC, absolute risk Disease activity was measured using the AS Disease Activity Score, including CRP (ASDAS); BASDAI response was defined as a 5% improvement or an absolute improvement of 2 points on a BASDAI scale of -1; ADA dose(s) not specified ATA negative ATA positive 32 Kneepkens et al. EULAR 213; Poster FRI426

33 33 PsA (general)

34 1-Year results from the ustekinumab PSUMMIT 1 and 2 trials 34 The long-term safety and efficacy of ustekinumab (UST, anti-il-12/23) in patients with active psoriatic arthritis (PsA) was assessed in the 52-week extensions of two phase 3 studies: PSUMMIT 1 1 and 2 2 PSUMMIT 1 1 Patients were DMARD-IR and/or NSAID-IR Patients with previous anti-tnf use were excluded PSUMMIT 1 N=615 1 PSUMMIT 2 N=312 2 Week UST 9 mg wk, 4, and Q12W (PSUMMIT 1: N=24) 1 (PSUMMIT 2: N=15) 2 UST 45 mg wk, 4, and Q12W (PSUMMIT 1: N=25) 1 (PSUMMIT 2: N=13) 2 PSUMMIT 2 2 Patients with previous anti-tnf use were eligible Randomization was stratified by site, weight ( 1 kg, >1 kg), and baseline MTX use PBO wk, 4, and Q12W (PSUMMIT 1: N=26) 1 (PSUMMIT 2: N=14) * Blinded early escape: Patients with <5% improvement in both TJC and SJC 1,2 * * Primary endpoint 2 ACR2 at Week 24 UST 9 mg wk 24, 28, and 4 UST 45 mg wk 24, 28, and 4 1. Kavanaugh et al. EULAR 213; Poster SAT Ritchlin et al. EULAR 213; Oral OP1

35 35 Efficacy of ustekinumab after 1 year of treatment in patients with active PsA (PSUMMIT 1/2) The long-term safety and efficacy of ustekinumab (UST, anti-il-12/23) was assessed in the 52-week extensions of two phase 3 studies: PSUMMIT 1 1 and 2 2 Patients (%) Response to UST 9 mg at week 52 in PSUMMIT 1 (n=24) ACR2 DAS28-CRP PASI75 Patients (%) 1 Response to UST (combined dose) at week 52 in PSUMMIT 2 (n=189) ACR2 6.6 PASI75 1 ACR2 (%) 59.3 Anti-TNF naive 38.9 Anti-TNF experienced UST was generally well tolerated, with no deaths or tuberculosis and similar rates of adverse events reported across doses in both studies Authors conclusions Both UST doses yielded improvements in PsA signs/symptoms with favorable and comparable safety profiles UST was effective in both anti-tnf-naïve and anti-tnf-experienced patients, with greater efficacy in anti-tnf-naïve patients ACR2, 2% improvement in American College of Rheumatology criteria; DAS28; Disease Activity Score including 28-joint count; PASI75, 75% reduction in Psoriasis Area and Severity Index Adult patients were randomized to receive UST 45 mg or 9 mg at wk, wk 4, and Q12W 1. Kavanaugh et al. EULAR 213; Poster SAT Ritchlin et al. EULAR 213; Oral OP1

36 Results from the apremilast PALACE 1 and PALACE 3 studies 36 Patients with active psoriatic arthritis (PsA) despite prior DMARD and/or biologic use were treated with the oral phosphodiesterase 4 inhibitor apremilast (APR) or placebo (PBO) 1,2 In PALACE 3, patients had at least one 2-cm psoriatic lesion at baseline 2 Randomization was stratified by baseline DMARD use; stable concurrent DMARD therapy was allowed (MTX, sulfasalazine, leflunomide, or combination) 2 PALACE 1 N=54 1 PALACE 3 N=55 Per protocol population N=486 2 Week Primary endpoint 2 ACR2 at Week 16 * Early escape: Patients with <2% reduction in both tender/swollen joint counts re-randomized to APR 3 or 2 mg if first randomized to PBO or remained on the initial APR dose 1,2 PALACE 1: Re-randomization of all remaining PBO patients 1 APR 3 mg BID (PALACE 1: N=168 1 ) (PALACE 3: N=159 2 ) APR 2 mg BID (PALACE 1: N=168 1 ) (PALACE 3: N=163 2 ) PALACE 1: + (N=53) 1 PALACE 1: + (N=54) 1 PBO (PALACE 1: N=168 1 ) * (PALACE 3: N=164 2 ) PALACE 1: + (N=24) 1 PALACE 1: + (N=23) Kavanaugh et al. EULAR 213; Oral LB1 2. Birbara et al. EULAR 213; Oral OP14

37 52-Week safety and efficacy of apremilast in patients with PsA (PALACE 1) 37 Patients (N=54) were treated with apremilast (APR) in the 52-week extension study to PALACE 1 At week 16, significantly more APR2 (31.3%; P=.14) and APR3 patients (4.%; P<.1) achieved an ACR2 (primary endpoint) vs placebo (PBO) patients (19.4%) Following the 24-week PBO-controlled trial, patients were randomized to APR2 or APR3 through week Week response rate of PsA patients treated with APR in PALACE 1 1 Patients (%) 63. ACR ACR APR2 (n=168) APR3 (n=168) 13.8 ACR7 Exposure-adjusted incidence rates for adverse events (AEs), severe AEs, and serious AEs were comparable for weeks -24 and No safety signals with respect to major cardiac events, malignancies, and opportunistic infections were observed No cases of lymphoma, tuberculosis, or tuberculosis reactivations were reported Author s conclusion: Patients receiving APR for up to 52 weeks continued to demonstrate meaningful clinical responses with an acceptable AE profile ACR2/5/7, 2%/5%/7% improvement in American College of Rheumatology criteria; APR2, APR 2 mg BID; APR3, APR 3 mg BID; BID, twice a day Kavanaugh et al. EULAR 213; Oral LB1

38 Safety and efficacy of apremilast in patients with PsA and current skin involvement (PALACE 3) 38 Patients (per protocol, N=486) with active psoriatic arthritis (PsA) and skin lesions were treated with apremilast (APR) in the placebo (PBO)-controlled PALACE 3 study for 24 weeks Patients were randomized to PBO, APR 2 mg BID (APR2), or APR 3 mg BID (APR3), and stable DMARD therapy was allowed Patients (%) 1 PBO APR2 APR3 P<.1 P<.5 P<.5 NS P<.5 P< NS P< n= NA ACR2 ACR2 * PASI5 PASI75 DAS28 <2.6 Primary endpoint Week 16 Response rate of PsA patients treated with APR in PALACE 3 Week 24 Comparable results were seen with APR monotherapy and in combination with DMARD(s) APR was generally well tolerated; serious AEs occurred in 9 PBO, 3 APR2, and 6 APR3 patients Author s conclusion: Patients receiving APR experienced significantly improved signs and symptoms of PsA and associated psoriasis compared with PBO, with no new safety signals ACR2, 2% improvement in American College of Rheumatology criteria; BID, twice a day; DAS28; Disease Activity Score including 28-joint count; DMARD, disease-modifying antirheumatic drug; PASI5/75, 5%/75% reduction in Psoriasis Area and Severity Index * Actual response rate includes all early escape patients who continued on originally randomized treatment; statistics not performed Birbara et al. EULAR 213; Oral OP14

39 39 RA (general)

40 Correlation between serum adalimumab levels and clinical response in RA patients Serum levels of adalimumab (ADA) and antibodies to ADA (ATA) were correlated with DAS28(ESR) scores in RA patients (N=56) who had been treated with ADA (doses unspecified) for >6 months 4 Relationship among ADA, ATA and DAS28(ESR), according to ADA tertiles ADA serum level tertiles Group 1 (n=22) <2.8 mg/l Group 2 (n=13) mg/l Group 3 (n=21) >7.3 mg/l ADA serum level, mg/l 1.56 ± ± 1.15* ± 4.45*, ATA detected 4 (18%) DAS28(ESR) 3.81 ± ±.92* 2.53 ±.68* * Statistically significant vs Group 1; statistically significant vs Group 2 Serum levels of ADA were inversely correlated with DAS28(ESR) scores (-.46; 95% CI: -.66 to -.21) Serum ADA levels needed to maintain clinical remission (DAS28 2.6) or low clinical activity (DAS ) were estimated based on ROC curves Remission: 3.1 mg/l (AUC, 65.77%; sensitivity, 5%; specificity, 77.77%) Low clinical activity: 3.48 mg/l (AUC, 83.18%; sensitivity, 83.33%; specificity, 77.8%) Authors conclusions There is a negative correlation between the serum level of ADA and DAS28 Serum level of ADA >7.3 mg/l does not increase DAS28 improvements, suggesting dose modulation may be considered in these patients AUC, area under the curve; DAS28, Disease Activity Score including 28-joint count; ESR, erythrocyte sedimentation rate; ROC, receiver operating characteristics Rosas et al. EULAR 213; Poster THU26

41 Comparison of the effects of ABA and ADA on remission and low-disease activity in patients with RA (AMPLE) 41 AMPLE is a phase 3b, randomized, investigator-blinded 2-year study on efficacy of abatacept (ABA) and adalimumab (ADA) Biologic-naïve patients with RA ( 5 years) with inadequate response to MTX 125 mg abatacept SC weekly (n=318) Concomitant MTX 4 mg adalimumab SC biweekly (n=328) n= % n= % 1 Year Key endpoints Primary endpoint: Non-inferiority of ACR2 response at 1 year Remission (DAS28[CRP] <2.6, CDAI 2.8, SDAI 3.3, RAPID3 <3, Boolean score 1) LDA (DAS28[CRP] 3.2, CDAI 1, SDAI 11, RAPID3 6) Fleischmann et al. EULAR 213; Poster SAT132

42 Comparison of the effects of ABA and ADA on remission and low-disease activity in patients with RA (AMPLE) 42 AMPLE: Biologic-naïve RA patients with inadequate response to MTX were randomized to receive SC abatacept (ABA; N=318) or adalimumab (ADA; N=328) in combination with stable MTX Patients meeting remission (REM) * or low disease activity (LDA) criteria after 1 year 1 ABA 125 mg QW ADA 4 mg QOW Patients (%) REM LDA REM LDA REM LDA REM LDA REM DAS28(CRP) Physical function and radiographic progression after 1 year were analyzed in early responders (remission or LDA at days 85 and 169) >6% of early responders were HAQ DI responders after 1 year (improvement.3u) >8% of early responders were radiographic nonprogressors after 1 year ( mtss 2.8) Authors conclusion: Through 1 year, patients treated with ABA or ADA in the AMPLE trial achieved comparable rates of remission and LDA Similar improvements in physical function and radiographic outcomes were also observed CDAI, Clinical Disease Activity Index; DAS28, Disease Activity Score including 28-joint count; HAQ DI, Health Assessment Questionnaire Disability Index; mtss, modified total Sharp score; SDAI, Simplified Disease Activity Index; * DAS28(CRP) <2.6, CDAI 2.8, SDAI 3.3, RAPID3 <3, Boolean score 1; DAS28(CRP) 3.2, CDAI 1, SDAI 11, RAPID3 6 RAPID3 CDAI SDAI Boolean Fleischmann et al. EULAR 213; Poster SAT132

43 Safety and efficacy of tocilizumab monotherapy and in combination with MTX in early RA 43 The clinical, radiographic, and safety profile of tocilizumab (TCZ) ± MTX vs MTX was evaluated in a randomized, blinded trial of MTX-naïve, early RA patients ( 2 years) TCZ 8 mg/kg (TCZ8) Q4W + MTX* (primary intervention) MTX-naïve, early RA patients ( 2 years) DAS28 >3.2 Elevated ESR or CRP Either 1 erosion, RF+, or anti-ccp+ N=1157 TCZ8 Q4W monotherapy TCZ 4 mg/kg (TCZ4) Q4W + MTX* MTX* Week 24 Primary endpoint: Proportion of patients achieving DAS28 remission (DAS28[ESR] <2.6) Week 14 *Patients who received MTX started at 7.5 mg QW, escalating to 2 mg QW by wk 8 Burmester et al. EULAR 213; Oral OP41

44 Safety and efficacy of tocilizumab monotherapy and in combination with MTX in early RA 44 Patients (ITT, N=1157) with early RA ( 2 years) were randomized to receive IV tocilizumab (TCZ) Q4W at 4 mg/kg (TCZ4) + MTX, 8 mg/kg (TCZ8) + MTX, TCZ8 monotherapy, or MTX alone for 14 weeks MTX doses started at 7.5 mg QW, escalating to 2 mg QW by wk 8 Results Primary endpoint: Significantly more patients receiving TCZ8 + MTX achieved DAS28 remission* at weeks 24 and 52 compared with those receiving MTX alone (P<.5) Statistically significant improvements in ACR2/5/7, mean mtss, and HAQ DI were also observed at wk 52 in the TCZ8 + MTX group compared to MTX alone Safety Incidences of adverse events (AEs) and serious AEs were similar across treatment groups, while serious infections were highest in patients on combination therapy 9 deaths were observed across all treatment groups Authors conclusions TCZ treatment resulted in improvements in signs/symptoms of RA, physical function, and in inhibition of structural joint damage in all treatment groups compared to MTX alone, with consistently greatest improvement in the TCZ8 + MTX group HAQ DI, Health Assessment Questionnaire Disability Index; mtss, modified total Sharp score * DAS28(ESR) <2.6 Burmester et al. EULAR 213; Oral OP41

45 Effects of continuing etanercept therapy in RA patients with stable low disease activity 45 Randomized trial to evaluate whether low disease activity or remission (LDA/REM) * can be maintained in patients taking etanercept (ETN) + MTX if ETN dose is reduced or discontinued Key inclusion criteria RA patient on ETN 5 mg/wk plus MTX Documented low disease activity or remission (DAS28 3.2) for 11 months Stable MTX (dose mg/wk) No prior biologics except anti-tnf, and no prior attempt to discontinue ETN due to stable disease 16 Patients screened 91 Patients enrolled No change to existing therapy 2 months Monitoring to ensure stable LDA/REM 73 Patients randomized ETN 5 mg/wk + MTX ETN 25 mg/wk + MTX PBO + MTX Week 48 Primary outcome % of non-failures at Week 48 * DAS Failure was defined as DAS28 >3.2 and an increase in DAS28.6; non-failures maintained LDA/REM (DAS28 3.2) van Vollenhoven et al. EULAR 213; Poster FRI185

46 Effects of continuing etanercept therapy in RA patients with stable low disease activity 46 RA patients (N=73) in stable LDA/REM* on etanercept (ETN) 5 mg/wk + MTX were randomized to 5 mg/wk ETN, 25 mg/wk ETN, or placebo (PBO) in addition to maintaining MTX Treatment failure was defined as a DAS28 >3.2 and an increase in DAS28.6, or disease progression as determined by investigator or patient; non-failures maintained LDA/REM Clinical response at week 48 Non-failures (maintained LDA/REM) 44% (OR=4.2; CI: ) P=.44 vs PBO ETN 25 mg ETN 5 mg PBO 52% (OR=4.2; CI ) P=.7 vs PBO Median time to failure (from randomization) 36 weeks 48 weeks 6 weeks 13% A greater likelihood of treatment failure was associated with the following baseline predictors (P<.1): higher erosion scores, higher VAS pain score, and shorter duration of ETN treatment prior to screening Adverse events were similar between groups Authors conclusions: For RA patients in stable LDA/REM on ETN + MTX, continued treatment with ETN at 5 mg/wk or 25 mg/wk provides a significantly higher likelihood of maintaining stable disease state over 48 wks than MTX monotherapy These data suggest that an induction-maintenance strategy may be feasible in some individual patients, even in established RA CI, confidence interval; DAS28, Disease Activity Score including 28-joint count; LDA/REM, low disease activity/remission; OR, odds ratio; VAS, visual analog scale * LDA/REM defined as DAS28 3.2, included patients maintained LDA/REM for for 11 months; Stable dose mg/wk van Vollenhoven et al. EULAR 213; Poster FRI185

47 Effect of withdrawing MTX in RA patients with moderate to severe RA (CAMEO) This prespecified post hoc analysis of the CAMEO trial assessed month 12 responses in patients with moderate disease activity (MDA, DAS ) or severe disease activity (SDA, DAS28 >5.1) at baseline Patients received ETN 5 mg/week + MTX for 6 months, then were randomized to either continue or discontinue MTX Mean DAS28 (95% confidence interval) 7 2 Post hoc analysis of DAS28 in patients with MDA/SDA (N=25) Randomization LDA (DAS28 <3.2) More patients in MDA reached LDA at month 6 compared to patients in SDA (61.3% [49/8] vs 35.8% [43/12]; OR=2.5, 95% CI: ) Authors conclusions: It may be possible to withdraw MTX in a relatively high proportion of patients, but those with initial SDA may need to continue combination therapy SDA MDA Month ETN + MTX (n=66) ETN (n=55) ETN + MTX (n=41) ETN (n=43) 47 DAS28, Disease Activity Score including 28-joint count; MTX, methotrexate Keystone et al. EULAR 213; Poster FRI161