Somatosensation encompasses a variety of essential modalities including touch, pressure, proprioception, temperature, pain, and itch. These peripheral sensations are crucial for all types of behaviors, ranging from social interaction to danger avoidance. Somatosensory information is transmitted from primary afferent fibers in the periphery into the central nervous system via the dorsal horn of the spinal cord. The dorsal horn functions as an intermediary processing center for this information, comprising a complex network of excitatory and inhibitory interneurons as well as projection neurons that transmit the processed somatosensory information from the spinal cord to the brain. It is now known that there can be dysfunction within this spinal cord circuitry in pathological pain conditions and that these perturbations contribute to the development and maintenance of pathological pain. However, the complex and heterogeneous network of the spinal dorsal horn has hampered efforts to further elucidate its role in somatosensory processing. Emerging optical techniques promise to illuminate the underlying organization and function of the dorsal horn and provide insights into the role of spinal cord sensory processing in shaping the behavioral response to somatosensory input that we ultimately observe. This review article will focus on recent advances in optogenetics and fluorescence imaging techniques in the spinal cord, encompassing findings from both in vivo and in vitro preparations. We will also discuss the current limitations and difficulties of employing these techniques to interrogate the spinal cord and current practices and approaches to overcome these challenges.

Objective To compare 2 years of radiographic sacroiliac joint (SIJ) changes in patients with recent onset axial spondyloarthritis (axSpA) receiving etanercept in a clinical trial (EMBARK) to similar patients not receiving biologics in a cohort study (DESIR). Methods Endpoints were changes at week 104 per the modified New York (mNY) grading system in total SIJ score (primary endpoint) and net percentage of patients with progression defined three ways. Treatment effect was analysed with and without adjustment for baseline covariates. Results At 104 weeks, total SIJ score improved in the etanercept group (n=154, adjusted least-squares mean change: –0.14) and worsened in the control group (n=182, change: 0.08). The adjusted difference between groups (etanercept minus control) was –0.22 (95% CI –0.38 to –0.06), p=0.008. The net percentage of patients with progression was significantly lower in the etanercept versus the control group for two of three binary endpoints: –1.9% versus 1.6% (adjusted difference for etanercept minus control: –4.7%,95% CI –9.9 to 0.5, p=0.07) for change in mNY criteria; –1.9% versus 7.8% (adjusted difference: –18.2%,95% CI –30.9 to –5.6, p=0.005) for change ≥1 grade in ≥1 SIJ; and –0.6% versus 6.7% (adjusted difference: –16.4%,95% CI –27.9 to –5.0, p=0.005) for change ≥1 grade in ≥1 SIJ, with shift from 0 to 1 or 1 to 0 considered no change. Conclusion Despite the slow radiographic SIJ progression rate over 2 years in axSpA, this study suggests a lower rate of progression in the SIJ with etanercept than without anti-tumour necrosis factor therapy. Trial registration numbers NCT01258738, NCT01648907; Post-results.

Objective. To evaluate the long-term clinical and imaging efficacy of etanercept in patients with early, active nonradiographic axial spondyloarthritis (SpA).Methods. Adult patients who satisfied the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA (but not the modified New York radiographic criteria), with symptom duration >3 months to <5 years, and who were unresponsive to >= 2 nonsteroidal antirheumatic drugs (NSAIDs) received double-blind etanercept 50 mg/week or placebo for 12 weeks, followed by open-label etanercept 50 mg/week to week 104. Clinical, magnetic resonance imaging (MRI; Spondyloarthritis Research Consortium of Canada [SPARCC] scores), and safety outcomes at 104 weeks were analyzed.Results. Of 215 randomized patients (etanercept: n=106; placebo: n=109), 205 entered the study (etanercept/etanercept: n=100; placebo/etanercept: n=105) and 169 completed the open-label period (etanercept/etanercept: n=83; placebo/etanercept: n=86). At week 104, 61 of 81 (75%), 49 of 81 (61%), 48 of 80 (60%), and 57 of 81 (70%) patients who received etanercept throughout the trial achieved ASAS20, ASAS40, Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease, and Bath Ankylosing Spondylitis Disease Activity Index criteria for 50% improvement (BASDAI 50) scores, respectively (observed). From baseline to week 104, continued improvements in clinical outcomes (ASDAS-C-reactive protein: -1.5 and -1.7; BASDAI: -3.3 and -3.8 [last observation carried forward]), and SPARCC MRI scores (sacroiliac joint: -6.0 and -3.4; spinal: -2.1 and -0.8 [observed]) were seen in patients receiving etanercept/etanercept and placebo/etanercept. During the study, 8% in the etanercept/etanercept group and 7% in the placebo/etanercept group had serious adverse events; no new safety signals were seen.Conclusion. Patients with early, active nonradiographic axial SpA and an inadequate response to at least 2 NSAIDs demonstrated improvement in clinical and imaging outcomes that were sustained through 104 weeks of etanercept treatment.

Background Demonstrating a structural effect of TNF inhibitors in axial SpA (axSpA) is challenging. Objectives To compare 2 yrs of structural lesion changes on T1W MRI in the sacroiliac joints (SIJ) of pts receiving etanercept (ETN) in a clinical trial to similar pts not receiving biologics in a cohort study. Methods Pts had recent onset non-radiographic (nr)-axSpA fulfilling ASAS criteria. Study group: pts receiving ETN 50 mg once weekly for 2 yrs in EMBARK (NCT01258738). Control group: pts in a longitudinal cohort study not receiving biologics for 2 yrs (DESIR, NCT01648907). Outcome measure: change in structural lesions of erosion, backfill, fat metaplasia, and ankylosis. MRI images were read by 3 experienced readers unaware of image chronology and pt group, using the SpondyloArthritis Research Consortium of Canada SIJ Structural Score (SSS).1 For each group, differences were calculated between percentages of patients experiencing increases and decreases in structural lesion scores over 2 yrs. Treatment effect was analyzed without and with adjustment for the baseline (BL) covariates of sex, symptom duration, smoking status, HLA-B27 status, ASDAS-CRP, SPARCC MRI SIJ score, and SIJ radiography score. Results At BL, pts with MRI images in the control (DESIR, N=76) and ETN (EMBARK, N=162) cohorts differed significantly in symptom duration, smoking status, ASDAS-CRP and SPARCC MRI SIJ score. The table presents structural lesion changes on MRI. The mean difference between control and ETN was significant for erosion (table). Figure shows cumulative probability plot. Conclusions This analysis confirms the slow rate of structural lesion progression in the SIJ over 2 yrs in nr-axSpA and suggests a lower rate of progression with ETN than without a TNF inhibitor. References Maksymowych WP, et al. J Rheumatol. 2015;42:79–86. Disclosure of Interest W. P. Maksymowych Grant/research support from: AbbVie, Pfizer, Sanofi, Consultant for: AbbVie, Amgen, Eli Lilly, Janssen Pharmaceutica, L.P, Novartis, Pfizer, Sanofi, UCB, M. Dougados Grant/research support from: Pfizer, Abbvie, UCB, Merck, Lilly, Sanofi, Consultant for: Pfizer, Abbvie, UCB, Merck, Lilly, Sanofi, R. G. Lambert Consultant for: Bioclinica, R. Landewe Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB, Wyeth, Consultant for: Abbott/Abbvie, Ablynx, Amgen, Astra-Zeneca, BMS, Celgene, Janssen (formerly Centocor), Galapagos, GSK, Novartis, Novo-Nordisk, Merck, Pfizer, Roche, Schering-plough, TiGenix, UCB, Wyeth, Employee of: Is a director of Rheumatology Consultancy BV, which is registered company under Dutch law, A. Molto Grant/research support from: Pfizer, UCB, Consultant for: Abbvie, BMS, MSD France- Merck, Pfizer, UCB, P. Claudepierre Grant/research support from: Pfizer, Roche-Chugai, MSD, Consultant for: Abbvie, BMS, Celgene, Janssen, Novartis, Merck, Pfizer, Roche, UCB, M. de Hooge: None declared, R. Bonin Shareholder of: Pfizer, Employee of: Pfizer, J. Bukowski Shareholder of: Pfizer, Employee of: Pfizer, H. Jones Shareholder of: Pfizer, Employee of: Pfizer, I. Logeart Shareholder of: Pfizer, Employee of: Pfizer, R. Pedersen Shareholder of: Pfizer, Employee of: Pfizer, A. Szumski Employee of: InVentiv Health, B. Vlahos Shareholder of: Pfizer, Employee of: Pfizer, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boeringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, UCB, Employee of: Director of Imaging Rheumatology bv.

Background Despite the well-known symptomatic and anti-inflammatory effect of TNF inhibitors in axial SpA (axSpA), demonstrating a structural effect is challenging. Objectives To compare 2 yrs of radiographic sacroiliac joint (SIJ) changes in pts receiving etanercept (ETN) in a clinical trial to similar pts not receiving biologics in a cohort study. Methods Pts had recent onset non-radiographic (nr)-axSpA fulfilling ASAS criteria. Study group: pts receiving ETN 50 mg once weekly for 2 yrs in EMBARK (NCT01258738). Control group: pts in an ongoing longitudinal cohort study not receiving biologics for 2 yrs (DESIR, NCT01648907). Outcome measure: change in x-ray SIJ score per mNY criteria (0–4 per SIJ). X-rays were read by 3 experienced readers unaware of image chronology and pt group. Primary endpoint: change (mean of 3 readers) in total SIJ score (-8 to +8). Binary endpoints: (1) shift from baseline (BL) mNY+ to wk-104 mNY- and vice versa; (2) change in SIJ score ≥1 (left or right SIJ); (3) change in SIJ score ≥1 in ≥1 SIJ, with change from 0 to 1 and from 1 to 0 considered no change. Treatment effect was analyzed without and with adjustment for the baseline (BL) covariates of sex, symptom duration, smoking status, HLA-B27 status, ASDAS-CRP, SPARCC MRI SIJ score, and SIJ radiography score. Results At BL, the control (DESIR, N=197) and ETN (EMBARK, N=164) cohorts differed significantly in all covariates listed above. The difference in change in total SIJ score for control vs ETN, adjusted for covariates, was small but significant: least-squares mean (95% CI): 0.08 (-0.03, 0.20) vs -0.14 (-0.26, -0.01); p=0.008. The table presents x-ray changes. When adjusted for covariates, the mean difference between control and ETN was significant for 2 of the 3 binary endpoints (table). Conclusions This analysis confirms the slow rate of radiographic SIJ progression over 2 yrs in nr-axSpA. The observed data suggest a lower rate of progression with ETN than without a TNF inhibitor. Disclosure of Interest M. Dougados Grant/research support from: Pfizer, Abbvie, UCB, Merck, Lilly, Sanofi, Consultant for: Pfizer, Abbvie, UCB, Merck, Lilly, Sanofi, W. P. Maksymowych Grant/research support from: AbbVie, Pfizer, Sanofi, Consultant for: AbbVie, Amgen, Eli Lilly, Janssen Pharmaceutica, L.P, Novartis, Pfizer, Sanofi, UCB, R. Landewe Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB, Wyeth, Consultant for: Abbott/Abbvie, Ablynx, Amgen, Astra-Zeneca, BMS, Celgene, Janssen (formerly Centocor), Galapagos, GSK, Novartis, Novo-Nordisk, Merck, Pfizer, Roche, Schering-plough, TiGenix, UCB, Wyeth, Employee of: Is a director of Rheumatology Consultancy BV, A. Molto Grant/research support from: Pfizer, UCB, Consultant for: Abbvie, BMS, MSD France- Merck, Pfizer, UCB, P. Claudepierre Grant/research support from: Pfizer, Roche-Chugai, MSD, Consultant for: Abbvie, BMS, Celgene, Janssen, Novartis, Merck, Pfizer, Roche, UCB, M. de Hooge: None declared, R. G. Lambert Consultant for: Bioclinica, R. Bonin Shareholder of: Pfizer, Employee of: Pfizer, J. Bukowski Shareholder of: Pfizer, Employee of: Pfizer, H. Jones Shareholder of: Pfizer, Employee of: Pfizer, I. Logeart Shareholder of: Pfizer, Employee of: Pfizer, R. Pedersen Shareholder of: Pfizer, Employee of: Pfizer, A. Szumski Employee of: InVentiv Health, B. Vlahos Shareholder of: Pfizer, Employee of: Pfizer, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boeringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, UCB, Employee of: Director of Imaging Rheumatology bv.

Background Radiological structural changes in the sacroiliac joint (SIJ) over time in non-radiographic axial spondyloarthrits (nr-axSpA) can be evaluated by measuring the progression from non-radiographic to radiographic damage status according to modified New York (mNY) criteria but also with other more sensitive methods.1,2 However, the question remains whether anti-tumor necrosis factor therapy can prevent this structural progression, particularly in patients with nr-axSpA. Objectives To evaluate radiographic progression in SIJ after 2 years of etanercept (ETN) treatment in nr-axSpA according to different outcome measures. Methods Study design: 104-week follow-up of patients enrolled in the EMBARK trial who received ETN either from baseline (active treatment arm) or week 12 (placebo [PBO] arm). Patients: Active nr-axSpA refractory to ≥2 NSAIDs. Study drug: ETN 50 mg once a week. Outcome measures: Pelvic X-rays were performed at both baseline and week 104. After anonymization, 3 trained readers evaluated the films blinded to chronology using the 0–4 grade scale of the mNY radiographic criteria for each (left and right) SIJ. Statistical analysis: X-rays from patients who completed the 104-week study were assessed. For continuous variables (e.g., total score from 0 to 8 for the left and right SIJ according to mNY grading), the mean score from the 3 readers was evaluated (bias was possible because readers knew that all patients were previously considered to have nr-axSpA); for binary variables (e.g., change from non-radiographic to radiographic axSpA, worsening of ≥1 grade in ≥1 SIJ and an absolute final value of ≥2 in the worsened joint), the score agreed upon by ≥2 readers was used for analysis. Results Of 215 randomized patients, 169 completed the open-label period at 104 weeks; 161 patients had X-rays available at both baseline and week 104. Only 1 patient was found to have satisfied mNY criteria for radiographic SIJ damage (ie, at least bilateral grade II or unilateral grade III) at baseline. Of 160 patients with mNY negative scores at baseline, none became mNY positive at week 104. The mean score (SD) for the total (left and right) SIJ (scale, 0–8) was 0.87 (0.83) at baseline and 0.88 (0.85) at week 104 (change, 0.01 [0.15]; P=0.386). No patients had both worsening of ≥1 grade in ≥1 SIJ and an absolute final value of ≥2 in the worsened joint. Conclusions This study suggests that, whatever the outcome measure, no structural radiological progression in the SIJ occurred after 2 years of etanercept treatment in patients with nr-axSpA. Given this study9s limitations, eg, lack of controls and inclusion of completers only, it is unclear whether this is an effect of etanercept. Additional studies using X-rays and MRI of the SIJ should be conducted to further address this question. References Van der Linden S, et al. Arthritis Rheum. 1984;27:361–8. Dougados M, et al. Arthritis Rheum. 2014;66(suppl 11):S234–5. Disclosure of Interest M. Dougados Grant/research support from: Pfizer, AbbVie, UCB, Merck, Eli-Lilly, Sanofi, Consultant for: Pfizer, AbbVie, UCB, Merck, Eli-Lilly, Sanofi, W. Maksymowych Grant/research support from: AbbVie, Consultant for: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen Pharmaceutica, L.P, Pfizer, UCB, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Celgene, Daiichi, Eli-Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, UCB, Employee of: Director of Imaging Rheumatology bv., R. Pedersen Shareholder of: Pfizer, Employee of: Pfizer, R. Bonin Shareholder of: Pfizer, Employee of: Pfizer, I. Logeart Shareholder of: Pfizer, Employee of: Pfizer, J. Bukowski Shareholder of: Pfizer, Employee of: Pfizer, H. Jones Shareholder of: Pfizer, Employee of: Pfizer

OBJECTIVE:To evaluate the efficacy and safety of etanercept (ETN) after 48 weeks in patients with early active non-radiographic axial spondyloarthritis (nr-axSpA). METHODS:Patients meeting Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA, but not modified New York radiographic criteria, received double-blind ETN 50 mg/week or placebo (PBO) for 12 weeks, then open-label ETN (ETN/ETN or PBO/ETN). Clinical, health, productivity, MRI and safety outcomes were assessed and the 48-week data are presented here. RESULTS:208/225 patients (92%) entered the open-label phase at week 12 (ETN, n=102; PBO, n=106). The percentage of patients achieving ASAS40 increased from 33% to 52% between weeks 12 and 48 for ETN/ETN and from 15% to 53% for PBO/ETN (within-group p value <0.001 for both). For ETN/ETN and PBO/ETN, the EuroQol 5 Dimensions utility score improved by 0.14 and 0.08, respectively, between baseline and week 12 and by 0.23 and 0.22 between baseline and week 48. Between weeks 12 and 48, MRI Spondyloarthritis Research Consortium of Canada sacroiliac joint (SIJ) scores decreased by -1.1 for ETN/ETN and by -3.0 for PBO/ETN, p<0.001 for both. Decreases in MRI SIJ inflammation and C-reactive protein correlated with several clinical outcomes at weeks 12 and 48. CONCLUSIONS:Patients with early active nr-axSpA demonstrated improvement from week 12 in clinical, health, productivity and MRI outcomes that was sustained to 48 weeks. TRIAL REGISTRATION NUMBER:NCT01258738.

Objective.Analyses were conducted to examine the baseline burden of illness and compare the effect of etanercept (ETN) versus placebo (PBO) on quality of life (QOL) in patients with nonradiographic axial spondyloarthritis (nr-axSpA) who failed nonsteroidal antiinflammatory drugs (NSAID).Methods.Patients fulfilling the Assessment of Spondyloarthritis International Society axSpA criteria, not meeting the modified New York criteria for ankylosing spondylitis (AS), who were symptomatic 3 months to 5 years, with a Bath AS Disease Activity Index score ≥ 4, and failed ≥ 2 NSAID were randomized to ETN 50 mg weekly or PBO (double-blind) for 12 weeks, followed by open-label ETN 50 mg for 92 weeks. Stable NSAID were allowed throughout our study. QOL outcomes over 24 weeks were analyzed using ANCOVA models.Results.At baseline, Multidimensional Fatigue Inventory (MFI; ETN mean 14.7, PBO mean 15.0), EQ-5D utility (0.52, 0.57), EQ-5D visual analog scale (56.5, 56.4), and Medical Outcomes Study (MOS) Sleep Index II (45.5, 48.1) were worse than population norms (6.6–8.0, 0.86, 82.5, and 25.8, respectively). At Week 12, Bath AS Patient Global Score, nocturnal and average back pain, MOS Short Form-36 (SF-36) physical component, and Work Productivity and Activity Index (WPAI) presenteeism and activity impairment favored ETN (p < 0.05). Nonsignificant improvements for ETN were seen in other WPAI domains, MFI, MOS-Sleep Index I and II, Hospital Anxiety and Depression Scale, EQ-5D utility score, and SF-36 mental component (p > 0.05). At Week 24, patients in the PBO group who had switched to ETN at Week 12 showed improvement in most QOL assessments, similar to that seen in patients receiving ETN for 24 weeks.Conclusion.Improvements favored ETN in QOL and productivity measures, with limited improvement on general QOL measures. Short disease duration, a short PBO-controlled period, and a wide range of QOL scores at baseline may have influenced improvements.

Background Our previous data show that Etanercept (ETN) has superior clinical and anti-inflammatory efficacy to placebo (PBO) in patients with non-radiographic axial spondyloarthritis (nr-axSpA) and inadequate response to NSAIDs in a 12 week double-blind PBO controlled trial. Objectives To examine clinical and anti-inflammatory efficacy of ETN at wk 48 (12 wk double blind followed by 36 wk open-label treatment phase). Methods Patients with symptom duration >3 mths–<5 yrs, fulfilling ASAS axSpA criteria without meeting radiographic criteria for ankylosing spondylitis, having BASDAI ≥4, and failure with ≥2 NSAIDs were enrolled and randomized to ETN 50 mg QW or PBO. Both groups continued stable NSAID therapy. After 12 wks all patients received ETN 50 mg open-label. Clinical assessments (ASAS, ASDAS, BASDAI, BASFI) and MRI of sacroiliac (SI) joint and spine were performed (SPARCC and ASspiMRI scoring methods). Analyses used an ANCOVA model with baseline scores, treatment, MRI sacroiliitis +/-, as variables. Results Of 215 initially randomized patients (mITT population), 205 entered the open label phase (ETN=100; PBO=105). The proportion of patients achieving ASAS40 by 12 wks (primary endpoint) was 33.3% of those treated with ETN and 14.7% of PBO treated patients, improving to 52.7% of patients in the combined groups by wk 48. MRI-SI joint inflammation was reduced from baseline to wk12 in ETN and PBO treatment groups by 56.7% and 16.4%, respectively, and 65.2% (combined treatment groups) by wk 48. SAE caused 1 discontinuation (pyrexia) between wks 12–48 and infections (the most frequent AE) occurred in 43/208 patients. Conclusions In patients with early, active nr-axSpA and an inadequate response to ≥2 NSAIDs, clinical and imaging outcomes improved from baseline to a greater extent with etanercept therapy than with PBO, during the first 12 weeks. In the ensuing 36 week open label period, these outcomes continued to improve. There were no new safety signals. Acknowledgements The study NCT01258738 was funded by Pfizer Inc. Medical writing support was provided by Rachael Profit of Engage Scientific, Envision Pharma Group, and was funded by Pfizer Inc. Disclosure of Interest W. Maksymowych Grant/research support: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck, Pfizer, Synarc, and UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck, Pfizer, Synarc, and UCB, Employee of: CaRE Arthritis Ltd, D. van der Heijde Grant/research support: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Chugai, Daiichi, Eli Lilly, GlaxoSmithKline, Janssen Biologics, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, and Vertex, Consultant for: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Chugai, Daiichi, Eli Lilly, GlaxoSmithKline, Janssen Biologics, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, and Vertex, Employee of: Imaging Rheumatology bv, M. Dougados Grant/research support: AbbVie, Celgene, Eli Lilly, Novartis, Pfizer, Roche, and Sanofi-Aventis, J. Sieper Consultant for: Abbott, Eli-Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Speakers bureau: Abbott, Eli-Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, J. Braun Grant/research support: Abbott, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, and UCB, G. Citera Grant/research support: Pfizer, Consultant for: Bristol-Myers Squibb, Pfizer, and Abbott., C. Miceli-Richard Grant/research support: AbbVie, Bristol-Myers Squibb, Janssen, and Pfizer, Consultant for: AbbVie, Bristol-Myers Squibb, Janssen, and Pfizer, J. Wei Grant/research support: Abbott, AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eli Lilly, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi-Aventis, and UCB, Consultant for: Abbott, AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eli Lilly, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi-Aventis, and UCB, R. Pedersen Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Bonin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, I. Logeart Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Wajdula Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, M. Rahman Employee of: Pfizer Inc at the time of the study, B. Vlahos Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Bukowski Shareholder of: Pfizer Inc, Employee of: Pfizer Inc DOI 10.1136/annrheumdis-2014-eular.1138

Background Anti-TNF agents are recommended treatment for NSAID-resistant radiographic ankylosing spondylitis (AS). Long-term quality of life (QoL) data available in axial spondyloarthritis (axSpA), prior to radiographic detection of change (i.e., non-radiographic [nr-axSpA]) are limited. Objectives To investigate long-term effects of etanercept (ETN) treatment on QoL in patients with nr-axSpA (who had an insufficient response to NSAID treatment) after 12 weeks of randomized treatment to ETN or placebo (PBO). Methods Enrolled patients fulfilling ASAS axSpA criteria, not meeting the modified New York criteria for AS, who were symptomatic for 3 months–5 years, with BASDAI ≥4, and failed ≥2 NSAIDs, were randomized to ETN 50 mg weekly or PBO (double blind) for 12 weeks followed by open-label ETN 50 mg. QoLs were recorded over a total of 48 weeks. Patients were allowed stable NSAID therapy throughout the study. Analyses used an ANCOVA model with baseline scores, treatment, and MRI sacroiliitis positive/negative status as variables. Results Of 208 participants who entered the open-label period (safety population; ETN=102; PBO=106) baseline mean age was 31.9 years; 60.6% were male, and mean disease duration was 2.5 years. By week 12, QoL improvements favoured ETN versus PBO in disease-specific, functional, and productivity domains such as BASDAI, BASFI, BAS-G, WPAI-AS, SF-36 physical component summary, and pain measures (P<0.05).1 During the open label phase, substantial improvements from baseline at weeks 24 and 48 were observed regardless of original 12-week treatment arm (table). Improvements with ETN treatment were sustained with little distinction between the groups receiving ETN for 12, 24 and 48 weeks. Conclusions In patients with early, active nr-axSpA and an inadequate response to ≥2 NSAIDs, ETN demonstrated improvement in QoL measures for disease specific and functional domains compared to PBO during the first 12 weeks.1 Improvements in PROs were rapid and sustained after all patients were treated with etanercept (weeks 12-48) and similar between original 12-week treatment groups. References Dougados M, et al. Arthritis Rheum. 2013;65(10):S656-657. Acknowledgements The nr-axSpA trial (ClinicalTrials.gov, NCT01258738) was sponsored by Pfizer Inc. Medical writing support was provided by Stephanie Eide of Engage Scientific Solutions and was funded by Pfizer Inc. Disclosure of Interest J. Sieper: None declared, E. Drescher: None declared, J. Rosa: None declared, R. Pedersen Employee of: Pfizer Inc., R. Bonin Employee of: Pfizer Inc., B. Vlahos Employee of: Pfizer Inc., J. Bukowski Employee of: Pfizer Inc., S. Kotak Shareholder of: Pfizer Inc., Employee of: Pfizer Inc. DOI 10.1136/annrheumdis-2014-eular.2242

ObjectiveTo assess the efficacy of etanercept in the treatment of early active nonsteroidal antiinflammatory drug (NSAID)–refractory nonradiographic axial spondyloarthritis (SpA).MethodsThe study population consisted of patients who met the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA but not the modified New York radiographic criteria for ankylosing spondylitis (as assessed by a radiologist at the central trial site), had a symptom duration of >3 months but <5 years, had a score of ≥4 on the Bath Ankylosing Spondylitis Disease Activity Index, and had been treated unsuccessfully with ≥2 NSAIDs. Patients were randomized to receive etanercept 50 mg/week or placebo and continued background NSAID treatment for 12 weeks (double‐blind study); during the subsequent open‐label period, all patients received etanercept 50 mg/week. The primary study end point was meeting the ASAS criteria for 40% improvement (ASAS40) at week 12. Magnetic resonance imaging (MRI) of the sacroiliac joints and spine was performed at baseline and week 12.ResultsOne hundred six patients were randomized to the etanercept group and 109 to the placebo group. Of the 215 patients, the mean ± SD age at baseline was 32.0 ± 7.8 years, 154 (72%) were HLA–B27 positive, and 174 (81%) had MRI‐confirmed sacroiliitis. At 12 weeks, the proportion of patients with improvement according to the ASAS40 was significantly higher in the etanercept group than in the placebo group (34 of 105 [32%] versus 17 of 108 [16%]; P = 0.006). Patients who received etanercept exhibited a greater reduction in MRI‐based scores for sacroiliac joint inflammation (−46.9% versus −10.9%; P < 0.001) and spinal inflammation (−45.4% versus −33.4%; P = 0.04) compared with placebo‐treated patients at week 12. Post hoc analyses suggested a possible association between higher baseline C‐reactive protein levels or MRI sacroiliac joint inflammation scores and higher rates of ASAS40 response to etanercept. At week 24, patients in the placebo group who had switched to etanercept at 12 weeks exhibited improvement similar to that observed in patients who had received etanercept for 24 weeks.ConclusionIn patients with nonradiographic axial SpA, etanercept treatment was associated with rapid, significant improvement in symptomatic disease activity, function, and systemic and skeletal inflammation over 12 weeks; clinical/functional improvement was sustained over 24 weeks.

Background Anti-TNF agents are currently recommended for the treatment of NSAID-resistant ankylosing spondylitis, but limited data are available on their efficacy in axial spondyloarthritis (axSpA), particularly non-radiographic axSpA (nr-axSpA). Objectives To compare the efficacy of etanercept (ETN) vs placebo (PBO) after 12 weeks of double-blind treatment in patients with nr-axSpA who had an insufficient response to NSAIDs. Methods Enrolled patients satisfied ASAS criteria for axSpA, without fulfilling modified NY criteria for ankylosing spondylitis (determined by central reading), had symptom duration of 3 months-5 years and a BASDAI score ≥4 despite current NSAID use, and had failed ≥2 NSAIDs (including current one). Patients were randomized to ETN 50 mg weekly or PBO and continued to receive background NSAID. Randomization was stratified by sacroiliitis (positive/negative on MRI by central reading according to ASAS criteria) and by geographic region. The primary endpoint was ASAS40 at week 12 (mITT). In addition to clinical assessments, MRI of the spine and sacroiliac (SI) joints was performed at baseline and week 12 and analyzed using the SPARCC scoring method (average of two independent central readers). Results At baseline, the mean age of patients was 32 years (range, 18-49 years); 61% were male; and mean disease duration was 2.4 years (range, 4 months-5 years). A total of 80.9%, 42.8%, and 87.9% were MRI+, had elevated CRP (CRP+), or were MRI+ and/or CRP+, respectively; 71.2% and 11.2% were HLA-B27+ or had psoriasis. Significantly more patients in the ETN group vs PBO group achieved ASAS40 (32.4% vs 15.7%; P=0.006) and most other clinical endpoints at week 12 (table); ETN was associated with significant improvements vs placebo in disease activity/function and inflammation on MRI. Conclusions In this population of patients with early, active nr-axSpA who had an inadequate response to ≥2 NSAIDs, etanercept was more effective than PBO in decreasing disease activity and inflammation on MRI. Acknowledgements This study was sponsored by Pfizer Inc. Medical writing support was provided by Donna McGuire of UBC Scientific Solutions and was funded by Pfizer Inc. Disclosure of Interest M. Dougados Grant/research support from: Abbott, LIlly, Pfizer, Roche, and UCB, Consultant for: (same), D. van der Heijde Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli-Lilly, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Vertex, Consultant for: (same), J. Sieper Consultant for: UCB, Speakers bureau: UCB, J. Braun Grant/research support from: Centocor, Amgen, Abbott, Roche, BMS, Novartis, Pfizer, and MSD, Consultant for: (same), W. P. Maksymowych Grant/research support from: Merck, Janssen, Amgen, Pfizer, Abbvie, Consultant for: (same + Eli Lilly), G. Citera Grant/research support from: Pfizer, Consultant for: Pfizer, Abbott, Bristol Myers Squibb, Roche, R. Pedersen Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Bonin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Bukowski Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, A. S. Koenig Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, B. Vlahos Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Alvarez Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

BACKGROUND:Many elderly female residents of long-term care facilities have osteoporosis and could benefit from intervention to increase bone density.OBJECTIVE:To examine the efficacy and safety of alendronate for treatment of osteoporosis in elderly female residents of long-term care facilities.DESIGN:Multicenter, randomized, double-blind, placebo-controlled 2-year study.SETTING:25 long-term care facilities.PATIENTS:327 elderly women with osteoporosis.INTERVENTION:Patients were randomly assigned to receive alendronate, 10 mg/d, or placebo. All patients also received vitamin D, 400 IU/d, and some patients received supplemental calcium (total intake, approximately 1500 mg/d).MEASUREMENTS:Bone mineral density (BMD) of the spine and hip and biochemical markers of bone turnover.RESULTS:Alendronate produced significantly greater increases in BMD than did placebo (24-month differences: spine, 4.4% [95% CI, 3.3% to 5.5%]; femoral neck, 3.4% [CI, 2.3% to 4.4%]). Alendronate produced greater decreases from baseline in biochemical markers of bone turnover than did placebo (P < 0.001).CONCLUSION:Alendronate increased BMD at both the spine and hip in elderly female residents of long-term care facilities.