Explore the vast range of titles available.

BackgroundSome rheumatoid arthritis (RA) patients (pts) may experience flares in their disease even after reaching stable low disease activity (sLDA), but the consequences of even temporary elevations in disease activity are poorly understood.ObjectivesThe purpose of this analysis was to explore the rates of flares after reaching sLDA in pts treated to target with either methotrexate (MTX) monotherapy or adalimumab combination therapy (ADA+MTX).MethodsThis post hoc analysis included pts from the randomised, double-blind, double-period OPTIMA1 trial achieving sLDA [DAS28(CRP) <3.2 at weeks (wks) 22 and 26] at the end of period 1 (P1). In P1, pts were randomised to receive ADA +MTX or placebo (PBO) +MTX for 26 wks. Pts on ADA +MTX achieving sLDA were randomised to receive PBO +MTX (ADA Withdrawal) or continue on ADA +MTX (ADA Continuation) for an additional 52 wks in period 2 (P2). Pts who achieved sLDA on PBO +MTX in P1 continued their treatment in P2 (MTX Continuation). Pts achieving sLDA in each treatment group were categorised based on whether they experienced a flare [change in DAS28(CRP) ≥0.6 at consecutive visits and DAS28(CRP) ≥3.2]; the proportion of pts experiencing flares and time to flare were assessed. For each group, mean change from wk 26 to wk 78 in disease activity [DAS28(CRP)], functional (HAQ-DI) and structural (mTSS) measures were analysed.ResultsIn pts achieving sLDA at the end of P1, flare rates in P2 differed based on initial treatment assignment (ADA Continuation: 11.7% [11/94]; MTX Continuation: 22.4% [22/98]). Interestingly, flare rates in pts randomised to withdraw ADA in P2 (ADA Withdrawal: 25% [22/88]) were numerically similar to the MTX Continuation group. The mean time to flare was 193, 191, and 177 days in the ADA Withdrawal, ADA Continuation, and MTX Continuation groups, respectively. During P2, the mean DAS28(CRP) scores were predictably higher in pts who flared compared with those who did not across treatment groups. In pts experiencing flares in P2, disease activity and functional measures worsened from wk 26 to wk 78 as compared with pts without flares (table 1). Of the individual DAS28(CRP) components, pt global assessment of disease activity (PtGA) showed the greatest worsening. There were small differences in radiographic progression between pts experiencing flares compared with pts without flares.Abstract AB0415 – Table 1Change from Week 26 in Disease Activity, Functional and Structural Measures Based on Flare Status in Patients Achieving Stable LDA**Flare was defined as change in DAS28(CRP) ≥0.6 at consecutive visits and DAS28(CRP) ≥3.2.LDA=low disease activity; DAS28(CRP)=28 joint disease activity score based on C-reactive protein; ADA=adalimumab; MTX=methotrexate; HAQ-DI=health assessment questionnaire disability index; mTSS=modified total Sharp score.ConclusionsIn early RA pts achieving sLDA, flares were generally infrequent; however, they were more prevalent in pts receiving PBO+MTX compared with ADA+MTX. Flares were numerically associated with higher disease activity, functional deterioration, and higher PtGA, underscoring its impact on health-related quality of life and the importance of preventing flares as a therapeutic outcome.Reference[1] Smolen JS, et al. Lancet2014;383:231–32.AcknowledgementsAbbVie funded the study (NCT00420927), contributed to its design, and participated in data collection, analysis and interpretation of the data, and in writing, review, and approval of the publication. Medical writing support was provided by Deepa Venkitaramani, PhD, of AbbVieDisclosure of InterestA. Kavanaugh Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB, Consultant for: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB, Speakers bureau: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB, R. van Vollenhoven Grant/research support from: AbbVie, Amgen, Biotest, BMS, Celgene, Crescendo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, and Vertex, Consultant for: AbbVie, Amgen, Biotest, BMS, Celgene, Crescendo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, and Vertex, Speakers bureau: AbbVie, Amgen, Biotest, BMS, Celgene, Crescendo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, and Vertex, P. Sunkureddi Consultant for: Novartis, Bristol-Myers Squibb, UCB, Pfizer, AbbVie, and Takeda, Speakers bureau: Novartis, Bristol-Myers Squibb, UCB, Pfizer, AbbVie, and Takeda, Y. Zhang Shareholder of: AbbVie, Employee of: AbbVie, J. Suboticki Shareholder of: AbbVie, Employee of: AbbVie, J. Smolen Grant/research support from: from AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Glaxo, Lilly, Pfizer, MSD, Novo Nordisk, Roche, Sandoz, and UCB, Consultant for: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Glaxo, Lilly, Pfizer, MSD, Novo Nordisk, Roche, Sandoz, and UCB

BackgroundGouty arthritis (GA) patients who experience frequent flares and have comorbidities have limited treatment options and need effective alternative treatments. Canakinumab (CAN), a selective, human, anti-interleukin-1β monoclonal antibody, has been approved in the European Union for the treatment of difficult-to-treat GA patients.ObjectivesA liquid formulation of CAN, presented as pre-filled syringe (CAN-PFS) has been developed to improve upon the lyophilized form (CAN-LYO) that requires reconstitution. A cumulative safety and efficacy results covering a total of 48 weeks are presented.MethodsGA patients completing the 12 week core study1 were enrolled in a 36 week open label extension (E1) study. All patients entering E1 received CAN-PFS 150 mg sc on demand upon new GA flare irrespective of assigned treatment during randomization [CAN-PFS, CAN-LYO or triamcinolone acetonide 40 mg (TA)]. The primary objective was to confirm the long-term safety of CAN-PFS vs TA. Secondary objectives included evaluation of CAN-PFS vs TA and CAN-LYO vs PFS for the time to first new flare over 48 weeks. Long-term safety outcomes and safety upon re-treatment were assessed as exposure-adjusted incidence rate of adverse events (AEs) and serious AEs (SAEs).ResultsOf 397 patients randomized in the core study, 232 (58.4%) entered E1, of which 198 (50%) completed E1. Baseline characteristics were comparable between the treatment groups. The exposure-adjusted incidence of AEs was lower for both CAN-PFS (254.9/100 pyr) and CAN-LYO (224.8/100 pyr) groups when compared with TA (362.7/100 pyr) over the 48 weeks. The exposure-adjusted incidence of SAEs was 14.7/100, 16.1/100, 15.5/100 pyr in patients randomized to CAN-PFS, CAN-LYO and TA groups, respectively. Infections and infestations were the most frequently reported SAE in the CAN-PFS (3.4/100 pyr), CAN-LYO (3.2/100 pyr), TA (0/100 pyr) groups. Over 48 weeks, one death (cardiac failure), not suspected to be related to study drug, was reported in a patient randomized to CAN-PFS who was not re-treated over 48 weeks. Overall, no new safety signals were observed in this extension study. CAN-PFS treatment significantly delayed time to first new flare vs TA patients with a relative risk reduction of 55% (HR, 0.45; 95% CI, 0.32 to 0.64; p<0.0001) over 48 weeks. The mean number of new GA flares per patient was lower for both CAN-LYO (0.50) and CAN-PFS (0.76) groups when compared with the TA group (0.96). Patients in the CAN-PFS group had a 56% reduction in the number of new flares compared to the TA group (rate ratio of 0.44, 95% CI 0.32 to 0.61, p<0.0001). However, both CAN treatments showed a similar mean flare rate per year (CAN-PFS, 0.95; CAN-LYO, 1.13).ConclusionsThese results further corroborate the long-term safety and efficacy of canakinumab liquid formulation in patients with frequent GA flares. The safety profile of canakinumab was consistent with the one observed in the core study and the efficacy of canakinumab pre-filled syringe was maintained upon re-treatment.ReferencesSunkureddi P, et al. Arthritis & Rheumatism 2013;65(10):S498.Disclosure of InterestR. Möricke: None declared, P. Sunkureddi Grant/research support from: Novartis, E. Toth: None declared, J. Brown Grant/research support from: Abvie, Amgen, Eli Lilly, Novartis, Pfizer, Roche, Takeda, Consultant for: Amgen, Eli Lilly, Speakers bureau: Amgen, Eli Lilly, U. Machein Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, G. Junge Employee of: Novartis, A. Kivitz: None declared

Background Lowering serum urate (SU) level is considered to be the mainstay of gouty arthritis (GA) therapy. SU levels below 6mg/dL favor dissociation of monosodium urate deposits (microtophi and visible tophi) in the joints and therefore these patients are less likely to flare. Objectives To explore the impact of baseline SU level on the occurrence of new flares in patients treated for acute GA with anti-inflammatory therapy. Methods A retrospective exploratory analysis using a multivariate logistic regression model predicting new flare was performed using the pooled data of 454 patients from two, pivotal 12-week, multicenter, double-blind, double dummy, active-controlled studies (β-RELIEVED and β-RELIEVED II). In these two studies, GA patients (meeting preliminary ACR-1977 criteria) with flare duration ≤5 days and contraindicated, intolerant or unresponsive to NSAIDs and/or colchicine were randomized to receive a single dose of canakinumab 150mg sc or triamcinolone acetonide (TA) 40mg im and were re-dosed “on demand” on each new flare. Patient’s baseline characteristics deemed to be indicative of GA disease severity were prescreened using a likelihood ratio test in a series of logistic regression models with treatment and a single covariate candidate. Results In a single predictor model, SU level was not found to be a statistically significant (p=0.21) predictor of new flare, while number of tophi locations, frequency of flares, and number of joints (>1) affected by acute GA flare were found highly significant predictors of new flare (p<0.05) in both the single predictor models and multivariate analysis. When added to the severity adjusted multivariate model, SU level appears to be a noise variable (p=0.50) compared to the triplet of the strongest determinants of reflare. Conclusions Results of this retrospective exploratory analysis show that baseline SU level was not a predictor of new flares in patients receiving anti-inflammatory therapy for acute GA, suggesting that GA severity may be more closely related to the prevention of flare than the baseline SU level. Disclosure of Interest P. Sunkureddi Consultant for: Novartis, Bristol Myers Squibb, UCB, Pfizer., Speakers Bureau: Novartis, Bristol Myers Squibb, UCB, Pfizer., N. Schlesinger Grant/Research support from: Novartis, Consultant for: Novartis, URL Pharma, Savient, Takeda, Rx Enzyme, Speakers Bureau: Novartis, Takeda, Savient, T. Kiechle Shareholder of: Novartis, Employee of: Novartis, A. Shpilsky Shareholder of: Novartis, Employee of: Novartis, A. So Grant/Research support from: Novartis, Consultant for: Novartis, Ardea, Speakers Bureau: Novartis, Ardea, Menarini

Background Chronic kidney disease (CKD) limits the treatment options in acute gouty arthritis (GA) patients due to intolerance and contraindications to available therapies. Efficacy and safety of canakinumab (CAN), a selective, fully human, anti-IL-1β monoclonal antibody, formulated as a lyophilized (CAN-LYO) powder requiring reconstitution with water vs triamcinolone acetonide (TA) in patients with acute GA was demonstrated in previous phase III trials. Objectives To evaluate efficacy and safety of CAN liquid formulation (CAN-PFS) vs TA in a subgroup of patients with CKD stage ≥3. Methods This was a 12-week, multicenter, double-blind, active controlled study. The design and methodology of the study have been reported earlier1. Here, we report results from a post-hoc analysis of the 12-week data for GA patients with CKD stage ≥3 (estimated Glomerular Filtration Rate (eGFR) <60ml/min). The primary endpoint was pain intensity in the target joint, measured on 0-100 mm VAS scale at 72 h post-dose. Secondary endpoints included time to first new attack, and safety over 12 weeks. Results Of 388 patients, 76 had CKD stage ≥3 at baseline (CAN-PFS, n=24; CAN-LYO, n=28; TA, n=24). CAN-PFS provided a statistically significant reduction in pain intensity in the target joint vs TA from 72 h post-dose (estimated difference, -14.6mm; 95% CI:-29.0, -0.1, p≤0.05) until 7 days post-dose (-16.1mm; 95% CI: -28.4, -3.7, p=0.0115). The two CAN treatment arms were comparable. Over 12 weeks, a single dose of CAN-PFS showed a significant relative risk reduction of 90% for time to first new gout attack vs TA [HR 0.10, 95% CI (0.01, 0.78); p≤0.05]. Adverse events (AEs) were reported in 12 (50%), 11 (39.3%) and 10 (41.7%) patients in CAN-PFS, CAN-LYO and TA groups, respectively. The most frequent AEs were infections (CAN-PFS, n=3 (12.5%); CAN-LYO, n=6 (21.4%); TA, n=2 (8.3%). Serious AEs were reported in a total of 7 patients (CAN-PFS, n=2 (8.3%); CAN-LYO, n=4 (14.3%); TA, n=1 (4.2%), with infections (CAN-PFS, n=1 (4.2%); CAN-LYO, n=2 (7.1%); TA, n=0), being the most common SAEs. No deaths were reported during the study. Conclusions This post-hoc analysis provides evidence for the efficacy of CAN-PFS compared with a potent long-acting corticosteroid in providing significant pain relief and reducing incidence of new attacks in GA patients with CKD stage ≥3 with limited treatment options. The safety profile in this sub population was consistent with that of the overall study population and with that known from previous studies. References Sunkureddi et al. Arthirits & Rheum 2013; 65. Disclosure of Interest P. Sunkureddi Consultant for: Novartis, Bristol Myers Squibb, Speakers bureau: Pfizer, Takeda, Bristol Myers Squibb, UCB, Amgen, Abbott, Shinogi, Savient, E. Toth: None declared, J. Brown Grant/research support: Amgen, Bristol Myers Squibb, Eli Lilly, Novartis, Merck, Pfizer, Roche, Servier, Sanofi-Aventis, Takeda, Warner Chilcott, Consultant for: Amgen, Eli Lilly, Merck, Warner Chilcott, Sanofi–Aventis, Speakers bureau: Amgen, Eli Lilly, Novartis, Merck, A. Kivitz Grant/research support: Novartis, A. Stancati Shareholder of: Novartis, Employee of: Novartis, D. Richard Shareholder of: Novartis, Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, R. Möricke: None declared DOI 10.1136/annrheumdis-2014-eular.1850

Background Canakinumab (CAN), a selective, fully human anti-IL-1β monoclonal antibody, is the only approved biologic in the European Union for the symptomatic treatment of adult patients (pts) with difficult-to-treat gouty arthritis (GA). A liquid formulation, presented as pre-filled syringe (CAN-PFS) has been developed to improve upon the lyophilized form (CAN-LYO) that requires reconstitution. Here, we report results from a post-hoc analysis of the 12-week data of a Phase III trial. Objectives To evaluate the efficacy and safety of CAN-PFS vs triamcinolone acetonide (TA) in a subset of difficult-to-treat GA pts defined as a) unable to use NSAIDs and colchicine due to contraindication, intolerance or lack of efficacy, and b) currently on urate-lowering therapy (ULT), or previously failed ULT or in whom ULT is otherwise contraindicated. Methods This was a 12-week, multicenter, double-blind, active controlled study. The design and methodology of the study have been reported earlier1. The primary efficacy measure was overall pain intensity in the most affected joint measured on VAS scale (0-100 mm) at 72 h post-dose. Secondary endpoints included time to first new attack and safety over 12 weeks. Results Of the 397 GA pts randomized, 106 (CAN-PFS, n=34; CAN-LYO, n=43; TA, n=29) met the subgroup definition. CAN-PFS provided a statistically significant reduction in pain intensity at 72 h post dose vs TA (estimated difference, -30.7mm; 95%CI: -42.1, -19.3, p≤0.05). The least square mean pain scores at 72 h post-dose for CAN -PFS and LYO, were14.7mm and 19.3mm, respectively; both lower than that for TA (45.4mm). CAN-PFS treatment significantly delayed time to first new attack vs TA with a relative risk reduction of 92% (HR, 0.08; 95%CI: 0.01, 0.63, p≤0.05) over 12 weeks. Adverse events (AEs) were reported in 12 (35.3%), 16 (37.2%) and 14 (48.3%) pts in CAN-PFS, CAN-LYO and TA groups, respectively. Serious AEs were reported in 7 pts [CAN-PFS, n=1 (2.9%); CAN-LYO, n=5 (11.6%); TA, n=1 (3.4%)], with infections [CAN-PFS, n=1 (2.9%); CAN-LYO, n=2 (4.7%); TA, n=0)] being the most common SAEs. One patient in the CAN-LYO group had serious aortitis, which was coded under vascular disorders system organ class, but adjudicated as an opportunistic infection by the independent adjudication committee. No deaths were reported during the study. Conclusions This analysis provides evidence for the efficacy of CAN in difficult-to-treat GA pts either in pre-filled syringe or lyophilized formulation compared to a potent long acting systemic corticosteroid. CAN-PFS provided better pain relief and reduced the risk of new attacks compared to TA. The safety profile in this population was consistent with that of the overall study population and with that known from previous studies. References Sunkureddi et al. Arthirits & Rheum 2013; 65. Disclosure of Interest P. Sunkureddi Consultant for: Novartis, Bristol Myers Squibb, Speakers bureau: Pfizer, Takeda, Bristol Myers Squibb, UCB, Amgen, Abbott, Shinogi, Savient, E. Toth: None declared, J. Brown Grant/research support: Amgen, Bristol Myers Squibb, Eli Lilly, Novartis, Merck, Pfizer, Roche, Servier, Sanofi-aventis, Takeda, Warner Chilcott, Consultant for: Amgen, Eli Lilly, Merck, Warner Chilcott, Sanofi-aventis, Speakers bureau: Amgen, Eli Lilly, Novartis, Merck, A. Kivitz Grant/research support: Novartis, A. Stancati Shareholder of: novartis, Employee of: novartis, D. Richard Shareholder of: Novartis, Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, R. Möricke: None declared DOI 10.1136/annrheumdis-2014-eular.1846

Background In gouty arthritis (GA) elevated serum urate (SU) levels lead to the monosodium urate (MSU) crystal deposition (tophi) in cartilage, tendon sheaths, and subcutaneous tissue. This usually appears late in the disease course and indicates disease severity. However, currently there is no quantitative measure to differentiate severe from less severe GA patients using spread of tophaceous disease. Objectives To develop a quantitative measure of GA severity by the number of tophi locations. Methods Pooled analysis of two 12-week studies (β-RELIEVED, N=230; β-RELIEVED II, N=226) followed by 12-week extensions, demonstrated a significant reduction in time to new flare in patients treated with canakinumab 150 mg s.c. vs. triamcinolone acetonide (TA) 40 mg i.m. (p<0.0001). Additional retrospective analysis was conducted to explore the impact of the spread of tophaceous disease on time to new flare. A new quantitative measure was derived by summation of tophi locations (right upper limb, left upper limb, right lower limb, left lower limb, and one “other”) resulting in a 6-point ordinal measurement scale. Number of tophi locations, using this scale, ranged from 0 to 5. The number of tophi locations was evaluated as a covariate in the Cox regression model using Wald Chi-Square test. Results The number of tophi locations revealed a high statistical significance along with treatment effect (p<0.0001 for both) i.e. the fewer the number of tophi locations, the longer the time to new flare. A similar result was obtained from Kaplan-Meier (K-M) analysis using log-rank test across the strata of 3 subgroups of tophi category (0, 1-2, 3-5) [Figure]. Conclusions Our results suggest that the number of locations to which tophaceous formations have spread throughout the body leading to systemic disease is an indicator of disease severity in GA. This quantitative measure is a strong predictor of delay of new flare (the higher the number of locations the less delay in reflares). Disclosure of Interest N. Schlesinger Grant/Research support from: Novartis, Consultant for: Novartis,URL Pharma, Savient, Takeda, Rx Ensyme, Speakers Bureau: Novartis, P. Sunkureddi Consultant for: Novartis, Bristol Myers Squibb, UCB, Pfizer, Speakers Bureau: Novartis, Bristol Myers Squibb, UCB, Pfizer, R. Alten Grant/Research support from: Novartis, Consultant for: Novartis, Speakers Bureau: Novartis, T. Bardin Grant/Research support from: Menarini, Consultant for: Novartis, Ipsen, Menarini, Ardea, Biocryst, Speakers Bureau: Novartis, A. Shpilsky Shareholder of: Novartis, Employee of: Novartis, T. Kiechle Shareholder of: Novartis, Employee of: Novartis, A. So Grant/Research support from: Novartis, Consultant for: Novartis, Ardea, Speakers Bureau: Novartis, Ardea, Menarini

Current diagnostic classification criteria recommend elevated titres of anti-cardiolipin (aCL) and/or anti-β2GPI antibody by ELISA IgG or IgM and/or lupus anticoagulant (LA) to confirm antiphospholipid syndrome (APS). Although IgA aPL antibodies have been shown to be pathogenic in animal models of APS, their clinical significance has remained elusive. We report four cases of exclusive IgA anti-β2GPI antibody sero-positivity with concomitant clinical manifestations associated with APS. Four of the five patients were LA negative. 1) Thirty-eight-year-old African-American female with SLE presented with resolving digital ulcers. Serum IgA anti-β2GPI antibody titres were 118.5 SAU (normal range: 0–20 SAU). 2) Twenty-seven-year-old African-American woman with SLE was evaluated for recent onset of severe headaches, unresponsive to analgesics and anti-migraine medications. MRI of the brain revealed hyper-intensities in the white matter in the frontal lobes. Serum IgA anti-β2GPI antibody titres were 29.1 Standard A Units (SAU). 3) Thirty-two-year-old Hispanic female with history of two unexplained miscarriages and negative serologies for SLE. Serum IgA anti-β2GPI antibody titres were 102.0 SAU. 4) Twenty-five-year-old white female with history of recent unexplained miscarriage in the 11th week of gestation and associated complaints of numbness and tingling in her hands. Her IgA anti-β2GPI antibody titre was 62.0 SAU. 5) Twenty-five-year-old African-American woman with SLE, positive for anti-Ro antibodies with a history of ischemic fingers, a pregnancy loss and recent pregnancy complicated due to pre-eclampsia. Her LA was positive and her IgA anti-β2GPI antibody titer was 186.0 SAU. This case series supports that elevated IgA anti-β2GPI antibody titres may identify additional patients who have clinical features of APS but who do not meet current diagnostic criteria.

Background Majority of gouty arthritis (GA) patients (pts) have comorbidities. Chronic kidney disease (CKD) can limit treatment options due to intolerance and contraindications to available therapies. Canakinumab, a fully human monoclonal anti-IL-1β antibody, may present a potential new therapeutic option for treating acute flare pain and delaying new flares in these pts. Objectives To evaluate the efficacy and safety of canakinumab in GA pts with CKD Stage 3 or worse. Methods In two 12-week multicenter, double-blind, double-dummy, active controlled studies (β-RELIEVED, N=228; β-RELIEVED II, N=226), pts aged ≥18-≤85 yrs meeting ACR 1977 preliminary criteria for acute GA and contraindicated, intolerant or unresponsive to NSAIDs and/or colchicine received one single dose of canakinumab 150 mg sc or triamcinolone acetonide (TA) 40 mg im and were re-dosed “on demand” on each new flare, followed by a 12-week extension where study completers received canakinumab 150 mg sc or TA 40 mg im only “on demand” upon a new flare. Here, we report a post-hoc efficacy and safety analysis of pooled 24-week data for GA pts with CKD stage 3 or worse (estimated Glomerular Filtration Rate (eGFR) <60mL/min). Results A total of 114 pts had baseline CKD stage 3 or worse (canakinumab: 65 pts; TA: 49 pts). Over 24 weeks, the probability of new GA flares was lower with canakinumab compared to TA corresponding to a significant relative risk reduction of 54% for time to first new GA flare (hazard ratio 0.46, 95% CI 0.24 to 0.88, p=0.0094[one sided p-value]). Median time to first new flare was >24 weeks with canakinumab vs 19 weeks (133 days) with TA. 73.8% of pts had adverse events (AEs) with canakinumab vs 53.1% with TA. The most frequent AEs (>5%) were hypertension (n=5, 7.7%) with canakinumab and arthralgia (n=3, 6.1%) with TA. Incidence of infections and infestations were higher with canakinumab (27.7%) vs TA (18.4%). Canakinumab showed greater reduction in microalbumin, albumin/creatinine ratio and creatinine levels compared to TA, while blood pressure changes between the groups were minimal (Table). Change from baseline to end of study in the other biochemical parameters (total cholesterol, estimate of the actual GFR [surface area], triglycerides, serum urate) were comparable in both canakinumab and TA groups. A total of 7 (10.8%) pts in canakinumab group experienced SAEs (pneumonia, angina pectoris, gastritis, hyperglycaemia, cerebrovascular accident and intracranial haemorrhage, chronic renal failure, prostatic specific antigen increased, device dislocation). No SAEs were reported with TA. One patient in canakinumab group died due to cerebrovascular accident. Table 1. Changes in blood pressure and biochemical parameters Mean changes from baseline to end of studyCanakinumab,Triamcinolone acetonide, 150 mg40 mg Blood pressure, mm/Hg (systolic, diastolic)–3.1, –0.6–4.4, 0.4 Micro albumin (urine), mg/L–81.245.1 Albumin/creatinine ratio (urine), mg/mmol–6.389.12 Creatinine, μmol/L–6.1–3.6 Conclusions CKD limits treatment choices in GA pts. Canakinumab reduced the risk of new flares compared with TA in this population of pts with CKD stage 3 or worse and limited treatment options. Disclosure of Interest P. Sunkureddi Consultant for: Novartis, Bristol Myers Squibb, UCB, Pfizer., Speakers Bureau: Novartis, Bristol Myers Squibb, UCB, Pfizer., T. Bardin Grant/Research support from: Menarini, Consultant for: Novartis, Ipsen, Menarini, Ardea, Biocryst, R. Alten Grant/Research support from: Novartis, Consultant for: Novartis, Speakers Bureau: Novartis, N. Schlesinger Grant/Research support from: Novartis, Consultant for: Novartis, URL Pharma, Savient, Takeda, Rx Enzyme, Speakers Bureau: Novartis, Takeda, Savient, M. Bloch Grant/Research support from: Novartis, T. Kiechle Shareholder of: Novartis, Employee of: Novartis, G. Krammer Shareholder of: Novartis, Employee of: Novartis, A. Shpilsky Shareholder of: Novartis, Employee of: Novartis, A. So Grant/Research support from: Novartis, Consultant for: Novartis, Ardea, Speakers Bureau: Novartis, Ardea, Menarini

BackgroundTofacitinib is an oral JAK inhibitor for the treatment of RA.ObjectivesTo evaluate tofacitinib 5 and 10 mg twice daily (BID) efficacy in patients (pts) with moderate vs severe RA.MethodsTofacitinib 5 and 10 mg BID efficacy data were obtained from 6 randomised double-blind Phase 3 studies of 6–24 months' duration. Tofacitinib was administered as monotherapy (NCT00814307 ORAL Solo; NCT01039688 ORAL Start) or with csDMARDs, mainly MTX (NCT00960440 ORAL Step; NCT00847613 ORAL Scan; NCT00856544 ORAL Sync; NCT00853385 ORAL Standard). Pts receiving MTX monotherapy (ORAL Start), or placebo (±csDMARDs) were combined as a single “placebo” group. Baseline (BL) disease severity was classified as moderate or severe using Disease Activity Score in 28 joints with erythrocyte sedimentation rate (DAS28: moderate 3.2 to ≤5.1; severe >5.1) and Clinical Disease Activity Index (CDAI: moderate 10 to ≤22; severe >22). Month 3 (M3) efficacy outcomes included: pts (%) achieving low disease activity (LDA; DAS28 ≤3.2, CDAI ≤10), remission (DAS28 <2.6, CDAI ≤2.8), HAQ-DI <0.5 (normal physical functioning), HAQ-DI improvement >0.22 and mean change from BL (Δ) in DAS28, CDAI and HAQ-DI. This post hoc analysis had no multiplicity adjustments.ResultsOverall, more pts had severe BL disease by DAS28 (91.0%) and CDAI (89.5%). The table shows BL disease characteristics and M3 efficacy outcomes for pts classified by BL DAS28 disease severity; CDAI classification demonstrated similar trends.BL characteristics were balanced between treatment groups in each disease severity category. M3 efficacy was significantly greater with tofacitinib 5 and 10 mg BID vs placebo, regardless of BL disease severity. As expected, larger proportions of tofacitinib-treated pts with moderate vs severe BL RA achieved LDA by either DAS28 (32.3–36.7% vs 13.8–19.1%) or CDAI (49.2–55.0% vs 26.0–31.7%). Similarly, a higher proportion of pts achieved remission in the moderate vs severe BL groups by DAS28 (20.0–22.8% vs 6.2–9.0%) or CDAI (11.5–12.1% vs 5.1–6.7%). A greater proportion of pts achieved HAQ-DI <0.5 with moderate vs severe RA classified by BL DAS28 (45.0–60.6% vs 24.5–30.0%) or BL CDAI (40.8–52.4% vs 24.7–30.4%). Greater improvements from BL in disease activity and HAQ-DI were seen for pts with severe vs moderate RA classified by BL DAS28 (Table), and by BL CDAI (Tofacitinib 5/10 mg BID ΔCDAI: -21.1/-23.0 vs -8.1/-9.4; ΔHAQ DI: -0.5/-0.6 vs -0.3/-0.4).ConclusionsTofacitinib 5 and 10 mg BID demonstrated efficacy in treating pts with moderate and severe RA with >7 years' mean disease duration. By M3, pts with severe vs moderate BL disease activity had greater improvements in disease activity and physical functioning; higher proportions of pts with moderate vs severe BL disease activity achieved remission, LDA or normal physical functioning. Interpretation of this post hoc analysis may be limited by the smaller sample size of the moderate disease group and the combining of mono- and combination-therapy results.AcknowledgementsThis study was sponsored by Pfizer Inc. Editorial support was provided by A Pedder of CMC and funded by Pfizer Inc.Disclosure of InterestS. Schwartzman Consultant for: Pfizer Inc, P. Sunkureddi Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, L. Takiya Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, M. Snyder Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, H. Fan Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Lukic Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Roberts Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, W. F. Rigby Grant/research support from: Amgen, Pfizer Inc, Roche, Consultant for: Bristol-Myers Squibb, Eli Lilly, Pfizer Inc, Roche

Current diagnostic classification criteria recommend elevated titres of anti-cardiolipin (aCL) and/or anti- beta sub(2)GPI antibody by ELISA IgG or IgM and/or lupus anticoagulant (LA) to confirm antiphospholipid syndrome (APS). Although IgA aPL antibodies have been shown to be pathogenic in animal models of APS, their clinical significance has remained elusive. We report four cases of exclusive IgA anti- beta sub(2)GPI antibody sero-positivity with concomitant clinical manifestations associated with APS. Four of the five patients were LA negative. 1) Thirty-eight-year-old African-American female with SLE presented with resolving digital ulcers. Serum IgA anti- beta sub(2)GPI antibody titres were 118.5 SAU (normal range: 0-20 SAU). 2) Twenty-seven-year-old African-American woman with SLE was evaluated for recent onset of severe headaches, unresponsive to analgesics and anti-migraine medications. MRI of the brain revealed hyper-intensities in the white matter in the frontal lobes. Serum IgA anti- beta sub(2)GPI antibody titres were 29.1 Standard A Units (SAU). 3) Thirty-two-year-old Hispanic female with history of two unexplained miscarriages and negative serologies for SLE. Serum IgA anti- beta sub(2)GPI antibody titres were 102.0 SAU. 4) Twenty-five-year-old white female with history of recent unexplained miscarriage in the 11th week of gestation and associated complaints of numbness and tingling in her hands. Her IgA anti- beta sub(2)GPI antibody titre was 62.0 SAU. 5) Twenty-five-year-old African-American woman with SLE, positive for anti-Ro antibodies with a history of ischemic fingers, a pregnancy loss and recent pregnancy complicated due to pre-eclampsia. Her LA was positive and her IgA anti- beta sub(2)GPI antibody titer was 186.0 SAU. This case series supports that elevated IgA anti- beta sub(2)GPI antibody titres may identify additional patients who have clinical features of APS but who do not meet current diagnostic criteria.