Background Rheumatoid Arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease of unknown etiology characterized by symmetric synovitis leading to cartilage damage1. Chronic and severe RA is associated with a 50% higher risk of death from cardiovascular disease (CVD) compared with healthy controls2. Moreover, Active RA is associated with an unfavorable lipid profile resulting in a higher atherogenic index3. Secukinumab, a fully human anti-IL-17A monoclonal antibody has shown to improve signs and symptoms of patients with active RA in this phase II trial4. Evaluation of the effect of secukinumab on lipids is potentially relevant as current guidelines recommend treatment if hypercholesterolemia is associated with elevated CV risk5. Objectives To report the effect of secukinumab on the lipid profile and atherogenic indexes in patients with active RA despite stable methotrexate (MTX) treatment. Methods Adult RA patients (n=237) on MTX were randomized equally to receive monthly s.c injections of secukinumab 25mg, 75mg, 150mg, 300mg or placebo. After Week (wk) 16, responders on secukinumab remained on the same dose whereas doses were escalated in non-responders at wk20 (except patients initially on 300mg who remained on the same dose). All placebo patients were switched to secukinumab 150mg. Patients were followed up to wk52. Primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at wk16. Results Demographics, baseline characteristics and lipid parameters were normal and comparable across all treatment groups. There was no effect of secukinumab on the lipid profile (Total Cholesterol, HDLc, LDLc, TG, Apo A-I and Apo B) during the first 16 wks of treatment in all treatment groups when compared to placebo. Atherogenic indices (TC/HDLc and Apo B/Apo A-I ratio also remained unchanged during first 16 wks of therapy (Table 1). In patients who switched from placebo to secukinumab 150mg at wk20, TC/HDLc and Apo B/Apo A-I ratios remained unchanged throughout the duration of the study (wk0-52). The efficacy and safety of this study group has been reported previously and did not report any CV event3. Conclusions Treatment with secukinumab was not associated with changes in the lipid profile or the atherogenic risk in patients with RA. References Voulgari PV. Expert Opin Emerg Drugs. 2009; 13:175-96. Avina-Zubieta JA. Arthritis Rheum. 2008; 59: 1690-7. Myasoedova E et al. Ann Rheum Dis. 2010; 69:1310-4. Mark C. Genovese. Arthritis Rheum. 2011;63(10[suppl]):S149-S150. Peters MJL et al. Int J Clin Prac 2010; 64:1440-3. Disclosure of Interest P. Durez: None Declared, M. Genovese Grant/Research support from: Novartis, H. Kellner: None Declared, C. Codding: None Declared, G. Ligozio Employee of: Novartis Pharmaceuticals Corporation, H. Richards Employee of: Novartis Pharma AG, C. Escrig Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG, S. Mpofu Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG

Published studies report chronic low-back pain (CLBP) prevalence in the U.S. to be 4-14%. Beyond pain control, assessing disability levels and sleep quality are important aspects of managing patients with CLBP. A phase-3 withdrawal study assessing 12-hour extended-release hydrocodone/acetaminophen (HC/APAP CR) treatment in subjects with CLBP, consisted of the following phases: Washout/Screening, 3-week Active-Drug Open-Label (OL), 12-week Double-Blind (DB) in which subjects were randomized to placebo, 1 or 2 tablets HC/APAP CR twice daily, and Taper/Follow-up. Primary endpoint and study design details are reported elsewhere. Disability level and pain-related sleep interference were assessed and are reported here. To assess disability levels, subjects were given the Roland-Morris Disability Questionnaire (RMDQ), a 24-item self-administered questionnaire, at OL and DB baselines and final visit. Sleep interference was examined at these time points, with additional assessments at weeks 2, 6, and 12. During the OL period, improvements in randomized subjects' disability were demonstrated by reductions in RMDQ scores (mean percent change: –52%) from OL-baseline to DB-baseline. Additionally, mean reduction in subject's assessment of pain-related sleep interference score from OL-baseline to end of the OL-period was 4.0 for all subjects randomized into the DB period. During the DB period, both HC/APAP CR groups demonstrated statistically significantly lower mean percent-change increase in RMDQ scores than the placebo group, from DB-baseline to final visit. More specifically, mean percent increase for RMDQ scores in the 1-tablet HC/APAP CR group was 112% compared to 244% in the placebo group (p<0.001). Similarly, statistically significantly lower mean increase in sleep interference was observed for the HC/APAP CR groups compared with the placebo group at week 2 (p<0.001), week 6 (p<0.001) and week 12 (p<0.003). Twice daily administration of both 1 and 2 tablets of HC/APAP CR improved disability scores and decreased pain-related sleep interference relative to placebo. Funded by Abbott Laboratories.

Analgesic efficacy and safety of hydrocodone/acetaminophen extended-release (HC/APAP CR) was assessed in subjects with moderate-to-severe chronic low-back pain (CLBP). Subjects with CLBP (n=773) were enrolled at 62 sites; study protocol and informed consent were IRB-approved. Study periods were: Washout/Screening, 3-week Active-Drug Open-Label, 12-week Double-Blind in which subjects were randomized to placebo, 1 or 2 tablets HC/APAP CR twice daily, and Taper/Follow-up. Primary efficacy endpoint was mean change from double-blind baseline to final evaluation in Subject's Assessment of CLBP Intensity (VAS). Safety was evaluated by adverse-event (AE) assessment. All results reported are from the Double-Blind period. 511 subjects were randomized and received °Ý1 dose of study drug; data for 507 were evaluated for efficacy. Most subjects were women (59%) and white (87%); mean age 48 years. Baseline variables were similar among the 3 groups. Mean change from baseline CLBP intensity was statistically significantly lower in subjects in the HC/APAP CR groups than in the placebo group (8.6, 2-tablet; 13.3, 1-tablet vs 22.2, placebo; p<0.05); no statistically significant difference was observed between HC/APAP CR groups. The superiority of treatment with both HC/APAP treatments compared to placebo treatment was consistent across multiple secondary efficacy endpoints. 89/169 (53%) subjects in the HC/APAP CR 2-tablet, 75/170 (44%) in the 1-tablet, and 79/172 (46%) in the placebo group reported °Ý1 AE. AEs in °Ý5% of subjects in any treatment group were nausea, constipation, diarrhea, and headache. Nine subjects reported serious AEs (2 in each HC/APAP CR group; 5 in placebo group); 28 subjects discontinued due to AEs (3% in placebo; 6% in 1-tablet; 7% in 2-tablet group). Both HC/APAP CR doses given twice daily were effective treatment for CLBP over the 12-week period. The safety profile of HC/APAP CR was consistent with known profiles of mu-opioid receptor agonists. Funded by Abbott Laboratories. Analgesic efficacy and safety of hydrocodone/acetaminophen extended-release (HC/APAP CR) was assessed in subjects with moderate-to-severe chronic low-back pain (CLBP). Subjects with CLBP (n=773) were enrolled at 62 sites; study protocol and informed consent were IRB-approved. Study periods were: Washout/Screening, 3-week Active-Drug Open-Label, 12-week Double-Blind in which subjects were randomized to placebo, 1 or 2 tablets HC/APAP CR twice daily, and Taper/Follow-up. Primary efficacy endpoint was mean change from double-blind baseline to final evaluation in Subject's Assessment of CLBP Intensity (VAS). Safety was evaluated by adverse-event (AE) assessment. All results reported are from the Double-Blind period. 511 subjects were randomized and received °Ý1 dose of study drug; data for 507 were evaluated for efficacy. Most subjects were women (59%) and white (87%); mean age 48 years. Baseline variables were similar among the 3 groups. Mean change from baseline CLBP intensity was statistically significantly lower in subjects in the HC/APAP CR groups than in the placebo group (8.6, 2-tablet; 13.3, 1-tablet vs 22.2, placebo; p<0.05); no statistically significant difference was observed between HC/APAP CR groups. The superiority of treatment with both HC/APAP treatments compared to placebo treatment was consistent across multiple secondary efficacy endpoints. 89/169 (53%) subjects in the HC/APAP CR 2-tablet, 75/170 (44%) in the 1-tablet, and 79/172 (46%) in the placebo group reported °Ý1 AE. AEs in °Ý5% of subjects in any treatment group were nausea, constipation, diarrhea, and headache. Nine subjects reported serious AEs (2 in each HC/APAP CR group; 5 in placebo group); 28 subjects discontinued due to AEs (3% in placebo; 6% in 1-tablet; 7% in 2-tablet group). Both HC/APAP CR doses given twice daily were effective treatment for CLBP over the 12-week period. The safety profile of HC/APAP CR was consistent with known profiles of mu-opioid receptor agonists. Funded by Abbott Laboratories.

Chronic pain patients and the physicians who treat them may have differing assessments of pain and the affect of treatment on their pain. The use of the Subject's Global Assessment (SGA) and Physician's Global Assessment (PGA) in clinical trials allows patients and physicians to assess pain with a standardized questionnaire during treatment. A phase-3 withdrawal study assessing 12-hour extended-release hydrocodone/acetaminophen (HC/APAP CR) treatment in chronic low-back pain (CLBP) consisted of the following periods: Washout/Screening, 3-week Active-Drug Open-Label (OL), 12-week Double-Blind (DB), in which subjects were randomized to placebo, 1 or 2 tablets HC/APAP CR twice daily, and Taper/Follow-up. Primary endpoint results and study design details are reported elsewhere. Subject's (SGA) and physician's (PGA) global assessment of Back Pain Status are reported here. Subjects' assessment of their Back Pain Status was evaluated using a 5-point categorical scale (ranges: very good to very poor). Physician's assessment of subject's back pain was evaluated based on a 5-point categorical scale (ranges: very mild to very severe). Both measures were evaluated at the OL-baseline, DB-baseline, week-2, week-6, and week-12 visits. At weeks 2, 6 and 12, statistically significantly greater proportions of subjects in the HC/APAP CR 2-tablet group assessed their CLBP favorably on the SGA compared with subjects in the placebo group. Additionally, statistically significantly greater proportions of subjects in the HC/APAP CR 1-tablet group assessed their CLBP favorably, at weeks 6 and 12, on the SGA compared with subjects in the placebo group. Similarly the distribution of PGA scores at weeks 2, 6, and 12, was statistically significantly superior for each HC/APAP CR treatment group compared to the placebo treatment group. Global assessments of CLBP status, as rated by both subjects and physicians, were more favorable in the both HC/APAP CR groups compared with the placebo group. Funded by Abbott Laboratories. Chronic pain patients and the physicians who treat them may have differing assessments of pain and the affect of treatment on their pain. The use of the Subject's Global Assessment (SGA) and Physician's Global Assessment (PGA) in clinical trials allows patients and physicians to assess pain with a standardized questionnaire during treatment. A phase-3 withdrawal study assessing 12-hour extended-release hydrocodone/acetaminophen (HC/APAP CR) treatment in chronic low-back pain (CLBP) consisted of the following periods: Washout/Screening, 3-week Active-Drug Open-Label (OL), 12-week Double-Blind (DB), in which subjects were randomized to placebo, 1 or 2 tablets HC/APAP CR twice daily, and Taper/Follow-up. Primary endpoint results and study design details are reported elsewhere. Subject's (SGA) and physician's (PGA) global assessment of Back Pain Status are reported here. Subjects' assessment of their Back Pain Status was evaluated using a 5-point categorical scale (ranges: very good to very poor). Physician's assessment of subject's back pain was evaluated based on a 5-point categorical scale (ranges: very mild to very severe). Both measures were evaluated at the OL-baseline, DB-baseline, week-2, week-6, and week-12 visits. At weeks 2, 6 and 12, statistically significantly greater proportions of subjects in the HC/APAP CR 2-tablet group assessed their CLBP favorably on the SGA compared with subjects in the placebo group. Additionally, statistically significantly greater proportions of subjects in the HC/APAP CR 1-tablet group assessed their CLBP favorably, at weeks 6 and 12, on the SGA compared with subjects in the placebo group. Similarly the distribution of PGA scores at weeks 2, 6, and 12, was statistically significantly superior for each HC/APAP CR treatment group compared to the placebo treatment group. Global assessments of CLBP status, as rated by both subjects and physicians, were more favorable in the both HC/APAP CR groups compared with the placebo group. Funded by Abbott Laboratories.

OBJECTIVES:This double-blind trial evaluated the efficacy and safety of abatacept or infliximab vs placebo. The primary objective of this study was to evaluate the mean change from baseline in Disease Activity Score (based on erythrocyte sedimentation rates; DAS28 (ESR)) for the abatacept vs placebo groups at day 197. METHODS:Patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) were randomised 3:3:2 to abatacept ( approximately 10 mg/kg every 4 weeks, n = 156), infliximab (3 mg/kg every 8 weeks, n = 165), or placebo (every 4 weeks, n = 110) and background MTX. Safety and efficacy were assessed throughout the study. RESULTS:Similar patient demographics and clinical characteristics were present at baseline between groups, with mean scores of approximately 1.7 for HAQ-DI and 6.8 for DAS28 (ESR). At 6 months, mean changes in DAS28 (ESR) were significantly greater for abatacept vs placebo (-2.53 vs -1.48, p<0.001) and infliximab vs placebo (-2.25 vs -1.48, p<0.001). For abatacept vs infliximab treatment at day 365, reductions in the DAS28 (ESR) were -2.88 vs -2.25. At day 365, the following response rates were observed for abatacept and infliximab, respectively: American College of Rheumatology (ACR) 20, 72.4 and 55.8%; ACR 50, 45.5 and 36.4%; ACR 70, 26.3 and 20.6%; low disease activity score (LDAS), 35.3 and 22.4%; DAS28-defined remission, 18.7 and 12.2%; good European League Against Rheumatism (EULAR) responses, 32.0 and 18.5%; and Health Assessment Questionnaire Disability Index (HAQ-DI), 57.7 and 52.7%. Mean changes in physical component summary (PCS) were 9.5 and 7.6, and mental component summary (MCS) were 6.0 and 4.0, for abatacept and infliximab, respectively. Over 1 year, adverse events (AEs) (89.1 vs 93.3%), serious AEs (SAEs) (9.6 vs 18.2%), serious infections (1.9 vs 8.5%) and discontinuations due to AEs (3.2 vs 7.3%) and SAEs (2.6 vs 3.6%) were lower with abatacept than infliximab. CONCLUSIONS:In this study, abatacept and infliximab (3 mg/kg every 8 weeks) demonstrated similar efficacy. Overall, abatacept had a relatively more acceptable safety and tolerability profile, with fewer SAEs, serious infections, acute infusional events and discontinuations due to AEs than the infliximab group. TRIAL REGISTRATION NUMBER:NCT00095147.

OBJECTIVE:To examine, in routine practice, the effectiveness and cost-effectiveness of oxycodone (OxyContin) compared with standard therapy for osteoarthritis pain.STUDY DESIGN:Open-label active-controlled randomized naturalistic 4-month study of oxycodone vs a combination of oxycodone-acetaminophen (Percocet).METHODS:Outcomes and health resource utilization data were collected by telephone interview. Effectiveness was measured among 485 patients as the proportion having at least 20% improvement from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index pain score. Quality-adjusted life-years (QALYs) were calculated from the Health Utilities Index 3 score. Cost-effectiveness was measured as cost per patient improved and the QALYs gained, using generic oxycodone-acetaminophen in the base case for the healthcare and societal perspectives. Uncertainty was evaluated using multiple 1-way sensitivity analyses and cost-effectiveness acceptability curves.RESULTS:Improvement occurred in 62.2% of patients with oxycodone and in 45.9% of patients with oxycodone-acetaminophen (P < .001). After adjustment for baseline differences, 0.0105 QALYs were gained with oxycodone compared with oxycodone-acetaminophen (P = .17). The mean societal costs per patient during 4 months were 7379 US dollars and 7528 US dollars for oxycodone and oxycodone-acetaminophen, respectively (P = .33). Oxycodone was more effective and less costly than oxycodone-acetaminophen based on the societal perspective (including costs associated with time lost). Based on the healthcare perspective (excluding costs associated with time lost), the cost-effectiveness of oxycodone was 4883 US dollars per patient improved and 75,810 US dollars per QALY gained. The base-case results were robust.CONCLUSIONS:From the societal perspective, oxycodone was more effective and less costly than oxycodone-acetaminophen. From the healthcare perspective, oxycodone (compared with generic oxycodone-acetaminophen) fell within the acceptable range of cost-effectiveness between 50,000 US dollars and 100,000 US dollars per QALY gained.

Recent literature and animal research has provided insight to potentially new analgesic targets for managing osteoarthritis (OA) pain. Primary afferent neurons located in affected joints express excessive amounts of abnormally functioning sodium (Na) channels on their surface in response to the inflammatory process. These Na channels may play an integral role in production of pain and hyperalgesia. Hence, the authors set out to conduct a 2-week, open-label, multicenter proof-of-concept study to evaluate the effectiveness and safety of lidocaine patch 5% monotherapy in adults with OA pain of the knee (n = 20). Patients with OA of one or both knees who were experiencing inadequate pain relief (defined as an average daily pain intensity of > 4 on a 0 to 10 pain scale) with their current analgesic regimen (i.e. APAP, NSAIDs, COX-2 inhibitors, tramadol) were enrolled and had all analgesic medications discontinued. Treatment with the lidocaine patch 5% resulted in significant improvements in the Western Ontario and McMaster Universities OA Index (WOMAC) pain, stiffness, physical function subscales and composite index (48.4, 41.1, 47.0, and 46.8% improvements respectively, p < 0.01). In addition, significant improvement was noted for pain intensity, pain relief, and pain interference with quality of life as measured by the Brief Pain Inventory (p < 0.05). The lidocaine patch 5% was generally well tolerated and no patients discontinued due to treatment-related adverse events. Given the open-label design, lack of a control group, and small sample size, the findings from our pilot study need to be confirmed by larger randomized controlled trials. Topical lidocaine patch 5% may provide clinicians with a novel, non-systemic therapy for OA pain with a unique mechanism of action.

Osteoarthritis is estimated to affect 40 million people in the United States and 70 to 90% of Americans over 75 years of age1,2. Annual costs associated with arthritis (direct medical expenses and lost wages) were estimated at $95 billion in 2000, and this cost will increase as its prevalence increases1. A number of pharmacologic interventions are used to manage osteoarthritis, including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), or cyclooxygenase-2 (COX-2) inhibitors asappropriate for mild-to-moderate pain; tramadol or opioid combinations for moderately severe pain, and opioids for severe pain2–4. Regardless of the pain severity, pharmacologic monotherapy may not be sufficient, and individuals with osteoarthritis pain often require combination therapy5.