A prospective phase II trial was conducted to assess the feasibility, tolerance, and efficacy of a device designed for selective removal of rheumatoid factor from the plasma of rheumatoid arthritis patients. The device contained terpolymer hydrogel-coated plates with chemically attached, aggregated human immunoglobulin G, and it operated as an immunoaffinity column. Sixty-one patients aged 25 to 73 underwent weekly plasmapheresis treatments (the primary therapy phase). During the trial, patients continued current rheumatoid arthritis medications without dose adjustments. All patients received two to six treatments (primary therapy). Responding patients were eligible to continue apheresis treatment every 2 to 6 weeks (maintenance therapy). No serious, untoward side effects were noted in the course of this study; of 640 treatments, only 2 (in different patients) were aborted, one because of complaints of dizziness and angioedema and the other because of chest tightness and shortness of breath. Except for a significant (p less than 0.05) decrease in serum iron, no significant changes in complete blood count, serum electrolytes, renal and hepatic function tests, or serum C3 and C4 were noted. Although the trial was not designed to determine clinical efficacy, patients noted less morning stiffness, longer time to onset of fatigue, and improved global pain assessment (p less than 0.004); significant objective improvements were noted in joint pain, tenderness, swelling, and the number of affected joints (p less than 0.001). One-half of the treated patients had at least a 50 percent improvement in objective measures of antirheumatic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

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Background Modification of signs and symptoms and improvement in quality of life are key goals for clinical management of RA patients (pts). Sarilumab (SAR) is the first fully human monoclonal antibody directed against the alpha subunit of the IL-6 receptor (IL-6Rα). In the phase 2 MOBILITY Part A trial, SAR administered SC in combination with MTX achieved its primary endpoint of ACR20 at week 12 and guided selection of 2 doses (150 and 200 mg q2w) studied in Phase 3. Objectives This post hoc analyis evaluates the relationship between EULAR responses at week 12 and change from baseline of 2 clinical and 2 laboratory parameters (sleep [VAS], FACIT, Hb and hsCRP). Methods Patients were randomized to 6 groups: placebo, SAR 100, 150, 200 mg every other week (q2w) and 100, 150 mg weekly (qw). Disease characteristics, including those for anemia (Hb), systemic inflammation (hsCRP), fatigue (FACIT) and sleep (VAS) scores, were collected at baseline and then every 2 weeks. Results Baseline characteristics were similar across all groups (n=306): mean age 52.2±12.3 yrs; 79% women; mean disease duration 7.8±8.1 yrs; RF+ 79.7%; mean hsCRP 2.8±3.0 mg/dL. The proportion of patients achieving improved PROs, Hb, hsCRP and a EULAR good response was higher in the 2 Phase 3 dose groups vs placebo. Table 1 shows improvement at week 12 in pt reported outcomes (PROs), Hb and hsCRP for pts achieving a EULAR good response; similar findings were seen with SAR vs placebo (data not shown). Only FACIT and sleep VAS improvements were significantly better in the evaluation by EULAR good response vs. other responses (p =0.0010 [FACIT], p=0.0151 [VAS]). The most common TEAEs reported in all SAR arms were infections (non-serious) 12-26%, neutropenia 0-20%, and ALT increase 0-6%. Eight patients (none in the 2 Phase 3 doses, 2 on placebo) experienced at least 1 treatment emergent SAE (1 death due to respiratory distress syndrome/cerebrovascular accident in 100mg q2w); of these 6 led to permanent treatment discontinuation. There were no infection-related SAEs in patients with grade 3 or 4 neutropenia. Image/graph Conclusions Sarilumab doses studied in Phase 3 resulted in a significantly higher proportion of RA patients with improved Hb, hsCRP and EULAR good responses compared to placebo. This preliminary evaluation of a subset of PROs in MOBILITY Part A shows improvements in FACIT and sleep VAS scores that correlated with achievement of a EULAR good response. Acknowledgements MOBILITY Part A trial (NCT01061736) was funded by Sanofi and Regeneron Disclosure of Interest M. Genovese Grant/research support from: Sanofi, Regeneron, Consultant for: Sanofi, Regeneron, R. Fleischmann Grant/research support from: Sanofi, Regeneron, Consultant for: Sanofi, Regeneron, S. Fiore Shareholder of: Sanofi, Employee of: Sanofi, A. Radin Shareholder of: Regeneron, Employee of: Regeneron, C. Fan Shareholder of: Sanofi, Employee of: Sanofi, T. Huizinga Grant/research support from: Sanofi, Regeneron, Consultant for: Sanofi, Regeneron

Objectives Final 5yr safety and efficacy results of subcutaneous golimumab (GLM)+/-MTX evaluated in a phase 3 trial (GO-BEFORE) of MTX-naïve pts with rheumatoid arthritis (RA) are reported. Methods Pts were randomized to PBO+MTX, GLM 100mg+PBO, GLM 50mg+MTX, or GLM 100mg+MTX q4w. PBO+MTX pts crossed over to GLM+MTX at wks 28 (blinded early escape) or 52 (pts with ≥1 swollen/tender joint). Pts continued treatment at wk52 (start of long-term extension). After the last pt completed wk52 and unblinding occurred, PBO+MTX pts could switch to GLM 50mg+MTX, MTX and corticosteroid use could be adjusted, and a one-time GLM dose change (50 → 100mg or 100 → 50mg) was permitted at investigator’s discretion. The last GLM injection was at wk252. Observed efficacy results (ACR20/50/70, DAS28-CRP, HAQ-DI, radiographic) by randomized treatment group and cumulative safety data are reported through wks 256 and 268, respectively. Results Of 637 randomized pts, 3 were never treated; 419 continued treatment through wk252, and 215 withdrew (111 for AE, 23 for lack of efficacy, 20 lost to follow-up, 53 for other reasons, 8 deaths). 402 completed the safety follow-up through wk268. Efficacy results are presented in the table. At wk 256, 84.3% of all pts had an ACR20, 93.9% had DAS28-CRP EULAR response, and 80.6% had improvement in HAQ-DI ≥0.25. Mean changes from baseline in total vdH-S score were small and 64% of pts randomized to GLM+MTX had no radiographic progression (ΔvdH-S≤0). The most common AEs were upper respiratory tract infection(29.4%), nausea(19.6%), bronchitis(16.6%), and increased alanine aminotransferase(16.1%); 11.9% of pts had an injection-site reaction. Through wk268, 204/616(33.1%) pts had an SAE; 17.5% of pts discontinued study agent due to AEs. Overall rates of serious infections, malignancies, and death were 12.2%, 3.4%, and 1.9%, resp. Of 595 pts with available samples, 58(9.7%) were positive for antibodies to GLM. Image/graph Conclusions The retention rate was high(66.1%) through 5yrs. GLM+MTX therapy resulted in maintained improvements in signs/symptoms of RA and in physical function, and inhibited structural damage progression long-term. No new safety signals were detected through 5years in MTX-naïve RA pts. Disclosure of Interest P. Emery Grant/research support from: Janssen R&D, LLC, R. Fleischmann Grant/research support from: Janssen R&D, LLC, I. Strusberg Grant/research support from: Janssen R&D, LLC, P. Durez Grant/research support from: Janssen R&D, LLC, P. Nash Grant/research support from: Janssen R&D, LLC, E. Amante Grant/research support from: Janssen R&D, LLC, M. Churchill Grant/research support from: Janssen R&D, LLC, W. Park Grant/research support from: Janssen R&D, LLC, B. Pons-Estel Grant/research support from: Janssen R&D, LLC, C. Han Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, T. Gathany Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Y. Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen R&D, LLC, S. Xu Shareholder o...

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