Oral Abstracts 7: RA ClinicalO37. Long-Term Outcomes of Early RA Patients Initiated with Adalimumab Plus Methotrexate Compared with Methotrexate Alone Following a Targeted Treatment Approach

Background: This analysis assessed, on a group level, whether there is a long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially treated with placebo (PBO) + MTX who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was a 78- week, randomized, controlled trial of ADA + MTX vs PBO + MTX in MTX-naïve early (<1 year) RA patients. Therapy was adjusted at week 26: ADA + MTX-responders (R) who achieved DAS28 (CRP) <3.2 at weeks 22 and 26 (Period 1, P1) were re-randomized to withdraw or continue ADA and PBO + MTX-R continued randomized therapy for 52 weeks (P2); IR-patients received open-label (OL) ADA + MTX during P2. This post hoc analysis evaluated the proportion of patients at week 78 with DAS28 (CRP) <3.2, HAQ-DI <0.5, and/or ΔmTSS ≤0.5 by initial treatment. To account for patients who withdrew ADA during P2, an equivalent proportion of R was imputed from ADA + MTX-R patients. Results: At week 26, significantly more patients had low disease activity, normal function, and/or no radiographic progression with ADA + MTX vs PBO + MTX (Table 1). Differences in clinical and functional outcomes disappeared following additional treatment, when PBO + MTX-IR (n = 348/460) switched to OL ADA + MTX. Addition of OL ADA slowed radiographic progression, but more patients who received ADA + MTX from baseline had no radiographic progression at week 78 than patients who received initial PBO + MTX. Conclusions: Early RA patients treated with PBO + MTX achieved comparable long-term clinical and functional outcomes on a group level as those who began ADA + MTX, but only when therapy was optimized by the addition of ADA in PBO + MTX-IR. Still, ADA + MTX therapy conferred a radiographic benefit although the difference did not appear to translate to an additional functional benefit. Disclosures: P.E., AbbVie, Merck, Pfizer, UCB, Roche, BMS—Provided Expert Advice, Undertaken Trials, AbbVie—AbbVie sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. R.F., AbbVie, Pfizer, Merck, Roche, UCB, Celgene, Amgen, AstraZeneca, BMS, Janssen, Lilly, Novartis—Research Grants, Consultation Fees. S.F., AbbVie—Employee, Stocks. A.K., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, UCB—Research Grants, Consultation Fees. H.K., AbbVie—Employee, Stocks. S.R., AbbVie—Employee, Stocks. J.S., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, GlaxoSmithKline, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB—Research Grants, Consultation Fees. R.V., AbbVie, BMS, GlaxoSmithKline, Human Genome Sciences, Merck, Pfizer, Roche, UCB Pharma—Consultation Fees, Research Support. Table 1.Week 78 clinical, functional, and radiographic outcomes in patients who received continued ADA + MTX vs those who continued PBO + MTX or added open-label ADA following an inadequate response ADA + MTX, n/N (%)a PBO + MTX, n/N (%)b Outcome Week 26 Week 52 Week 78 Week 26 Week 52 Week 78 DAS28 (CRP) <3.2 246/466 (53) 304/465 (65) 303/465 (65) 139/460 (30)*** 284/460 (62) 300/460 (65) HAQ-DI <0.5 211/466 (45) 220/466 (47) 224/466 (48) 150/460 (33)*** 203/460 (44) 208/460 (45) ΔmTSS ≤0.5 402/462 (87) 379/445 (86) 382/443 (86) 330/459 (72)*** 318/440 (72)*** 318/440 (72)*** DAS28 (CRP) <3.2 + ΔmTSS ≤0.5 216/462 (47) 260/443 (59) 266/443 (60) 112/459 (24)*** 196/440 (45) 211/440 (48)*** DAS28 (CRP) <3.2 + HAQ-DI <0.5 + ΔmTSS ≤0.5 146/462 (32) 168/443 (38) 174/443 (39) 82/459 (18)*** 120/440 (27)*** 135/440 (31)** aIncludes patients from the ADA Continuation (n = 105) and OL ADA Carry On (n = 259) arms, as well as the proportional equivalent number of responders from the ADA Withdrawal arm (n = 102). bIncludes patients from the MTX Continuation (n = 112) and Rescue ADA (n = 348) arms. Last observation carried forward: DAS28 (CRP) and HAQ-DI; Multiple imputations: ΔmTSS. ***P < 0.001 and **iP < 0.01, respectively, for differences between initial treatments from chi-squar

Evaluation of a training program for persons with SCI paraplegia using the Parastep®1 ambulation system: Part 5. Lower extremity blood flow and hyperemic responses to occlusion are augmented by ambulation training

Objective: To test whether 12 weeks of exercise conditioning using functional neuromuscular stimulation (FNS) ambulation alters the resting lower extremity blood flow and hyperemic responses to vascular occlusion in subjects with paraplegia, and to determine whether an association exists between limb flow and lower extremity fat-free mass. Design: Pretest, posttest. Setting: Academic medical center. Participants: Subjects with chronic neurologically complete paraplegia. Intervention: Thirty-two sessions of microprocessor-controlled ambulation using electrically stimulated contractions of lower extremity muscles and a rolling walker. Outcome Measures: Subjects underwent quantitative Doppler ultrasound examination of the common femoral artery (CFA) before and after training. End-diastolic arterial images and arterial flow-velocity profiles obtained at rest and after 5 minutes of suprasystolic thigh occlusion were computer-digitized for analysis of heart rate (HR), CFA peak systolic velocity (PSV), CFA cross-sectional area (CSA), flow velocity integral (FVI), pulse volume (PV), and CFA (arterial) inflow volume (AIV). Results: Significant effects of training on CSA ( p < .0001), FVI ( p < .05), computed PV ( p < .001), and computed AIV ( p < .01) were observed. Resting HR was lower following training ( p < .05). The change for resting PSV approached but did not reach significance ( p = .083). Analysis of postocclusion PV and AIV showed significant effects for conditioning status ( p values < .01), postcompression time ( p values < .0001), and their interaction ( p values < .01). At 1 minute after occlusion, the posttraining AIV response was 78.2% greater in absolute magnitude and 17.4% more robust when expressed as a percentage change from its resting value than before training. Significant correlations were found between thigh fat free mass and both AIV and PV ( p values < .05). Conclusion: Exercise training using FNS ambulation increases the resting lower extremity AIV in individuals with paraplegia and augments the hyperemic response to vascular occlusion. Improved posttraining blood flow is attributable both to vascular structural changes and upregulation of vascular flow control mechanisms. Limb mass is associated with the volume of arterial blood flow

Evaluation of a training program for persons with SCI paraplegia using the Parastep®1 ambulation system: Part 1. Ambulation performance and anthropometric measures

Objective: To describe performance parameters and effects on anthropometric measures in spinal cord injured subjects training with the Parastep® 1 system. Design: Before-after trial. Setting: Human spinal cord injury applied research laboratory. Participants: Thirteen men and 3 women with thoracic (T4–T11) motor-complete spinal cord injury: mean age, 28.8yrs; mean duration postinjury, 3.8yrs. Intervention: Thirty-two functional neuromuscular stimulation ambulation training sessions using a commercially available system (Parastep-1). The hybrid system consists of a microprocessor-controlled stimulator and a modified walking frame with finger-operated switches that permit the user to control the stimulation parameters and activate the stepping. Outcome Measures: Distance walked, time spent standing and walking, pace, circumferential (shoulders, chest, abdomen, waist, hips, upper arm, thigh, and calf) and skinfold (chest, triceps, axilla, subscapular, supraillium, abdomen, and thigh) measurements, body weight, thigh cross-sectional area, and calculated lean tissue. Results: Statistically significant changes in distance, time standing and walking, and pace were found. Increases in thigh and calf girth, thigh cross-sectional area, and calculated lean tissue, as well as a decrease in thigh skinfold measure, were all statistically significant. Conclusions: The Parastep® 1 system enables persons with thoracic-level spinal cord injuries to stand and ambulate short distances but with a high degree of performance variability across individuals. The factors that influence this variability have not been completely identified

Treatment Algorithms in Systemic Lupus Erythematosus

ObjectiveTo establish agreement on systemic lupus erythematosus (SLE) treatment

Treatment algorithms in systemic lupus erythematosus

To establish agreement on systemic lupus erythematosus (SLE) treatment.SLE experts (n = 69) were e-mailed scenarios and indicated preferred treatments. Algorithms were constructed and agreement determined (≥50% respondents indicating ≥70% agreement).Initially, 54% (n = 37) responded suggesting treatment for scenarios; 13 experts rated agreement with scenarios. Fourteen of 16 scenarios had agreement as follows: discoid lupus: first-line therapy was topical agents and hydroxychloroquine and/or glucocorticoids then azathioprine and subsequently mycophenolate (mofetil); uncomplicated cutaneous vasculitis: initial treatment was glucocorticoids ± hydroxychloroquine ± methotrexate, followed by azathioprine or mycophenolate and then cyclophosphamide; arthritis: initial therapy was hydroxychloroquine and/or glucocorticoids, then methotrexate and subsequently rituximab; pericarditis: first-line therapy was nonsteroidal antiinflammatory drugs, then glucocorticoids with/without hydroxychloroquine, then azathioprine, mycophenolate, or methotrexate and finally belimumab or rituximab, and/or a pericardial window; interstitial lung disease/alveolitis: induction was glucocorticoids and mycophenolate or cyclophosphamide, then rituximab or intravenous gamma globulin (IVIG), and maintenance followed with azathioprine or mycophenolate; pulmonary hypertension: glucocorticoids and mycophenolate or cyclophosphamide and an endothelin receptor antagonist were initial therapies, subsequent treatments were phosphodiesterase-5 inhibitors and then prostanoids and rituximab; antiphospholipid antibody syndrome: standard anticoagulation with/without hydroxychloroquine, then a thrombin inhibitor for venous thrombosis, versus adding aspirin or platelet inhibition drugs for arterial events; mononeuritis multiplex and central nervous system vasculitis: first-line therapy was glucocorticoids and cyclophosphamide followed by maintenance with azathioprine or mycophenolate, and then rituximab, IVIG, or plasmapheresis; and serious lupus nephritis: first-line therapy was glucocorticoids and mycophenolate, then cyclophosphamide then rituximab.We established variable agreement on treatment approaches. For some treatment decisions there was good agreement between experts even if no randomized controlled trial data were available