Background: The musculoskeletal organ system BILAG-2004 (MSK BILAG) assessment is of critical importance in SLE clinical trials. Severe active polyarthritis, MSK BILAG A, by definition includes significant impairment of basic activities of daily living (ADLs), as opposed to MSK BILAG C, D, or E where ability to perform ADLs is expected to be preserved. In clinical trials, BILAG is scored by clinicians without formal review of patient reported outcomes (PROs). The Physical Health domain of the LupusQoL (LQol PH) (range 0 – 100) can be used to assess the patient’s physical function and ADLs. LQoL PH score thresholds defining impairment severity have not been established; however, a transformed LQoL PH score ≤50 suggests more impaired function, which would not be expected in MSK BILAG C, D, or E. Conversely, a score >50 implies no major issues with ADLs, which would be contradictory to the definition of MSK BILAG A. Objectives: To assess correlation of patient reported LQoL PH with MSK BILAG scores recorded by clinicians at various timepoints using data from the phase 3 TULIP studies 1,2 and to investigate the percent of discordance between patients and clinicians. Methods: Data from TULIP 1 and 2 studies (anifrolumab 300 mg and placebo arms) were pooled to evaluate the relationship between LQoL PH and MSK BILAG scores at baseline, weeks 24 and 52 using Spearman correlations as post-hoc analysis. Mean LQoL PH scores were assessed for each MSK BILAG category at the three timepoints using one-way ANOVA. Percent of patients with MSK BILAG A and LQoL PH scores >50 and patients with MSK BILAG C, D, or E and LQoL PH scores ≤50 was calculated at baseline, week 24 and 52. MSK BILAG B was excluded from the analysis because discordance could not be easily defined for this category compared with the more extreme MSK BILAG categories. Results: Total of 690 patients were included in the pooled analysis (Table 1). Significant correlations between LQoL PH and MSK BILAG scores were found at each time point (nominal p<0.0001); this relationship became stronger over time. Mean LQoL PH scores were different in each MSK BILAG category, with the highest in MSK BILAG D/E and the lowest in the MSK BILAG A category, thus confirming the discriminatory ability of the LQoL PH (Table 1). Table 1. Correlation coefficients (CC) between LQoL PH and MSK BILAG scores, and mean LQoL PH scores with standard deviations (SD) per each MSK BILAG category at baseline, weeks 24 and 52. Baseline Week 24 Week 52 CC N CC N CC N Total Population -0.25 690 -0.36 626 -0.41 552 MSK BILAG Mean LQoL PH Score (SD) Mean LQoL PH Score (SD) Mean LQoL PH Score (SD) 0 (D/E) 69.3 (24.7) 17 74.2 (22.1) 186 74.5 (21.3) 237 1 (C) 62.3 (25.4) 60 64.0 (23.9) 233 60.6 (22.5) 184 8 (B) 56.6 (24.4) 398 55.1 (24.2) 163 51.3 (24.3) 105 12 (A) 44.9 (25.8) 215 43.9 (25.9) 44 44.2 (26.2) 26 At baseline, 40% of patients who were assessed by clinicians as having MSK BILAG A reported minimal impairment in physical function and ADLs (LQoL PH >50) and 24.1% who had MSK BILAG C, D, or E reported difficulties with ADLs (LQoL HP ≤50), suggesting discordance between patients and clinicians. This discordance slightly decreased over time (Figure 1). Figure 1. Percent of patients with MSK BILAG A and LQoL PH scores >50 and patients with MSK BILAG C, D, or E and LQoL PH scores ≤50 at baseline, weeks 24 and 52. Conclusion: Patient reported LQoL PH scores correlated with MSK BILAG scores and showed discriminant validity for MSK BILAG scores. Greater discordance was seen between LQoL PH and MSK BILAG A compared with C, D, or E. These findings suggest a need for further investigation of a role for PROs in MSK BILAG scoring. Formal review of PROs by clinicians during MSK BILAG assessment could be considered in future SLE clinical trials. References: [1]Furie R et al. Lancet 2019 [2]Morand EF et al. N Engl J Med 2020 Acknowledgements: This study was sponsored by AstraZeneca. Disclosure of Interests: Ewa Olech Speakers bureau: Abbvie, Amgen, Merck, Pfizer, and UCB, Grant/research support from: BMS, Donald Stull: None declared, Betsy Williams: None declared, Stephanie Bean: None declared, Gabriel Abreu Employee of: AstraZeneca, Erik Schwetje Employee of: AstraZeneca, Raj Tummala Employee of: AstraZeneca, Sean O’Quinn Shareholder of: AstraZeneca, Employee of: AstraZeneca

Background: Randomized controlled trials in Systemic Lupus (SLE) have shown disappointing results for decades. Key challenges may include the heterogenous population coupled with high placebo response rates. Objectives: To evaluate trends in SLE study metrics over time and explore associations between primary endpoint failure and response in placebo/standard of care arms. Methods: Data from Phase II or III trials which enrolled ≥ 100 patients with SLE and reported SRI-4 and/or BICLA responses after a minimum of 24 weeks were included in the analysis. Sample size, recruitment rates, regional patient distributions, and results in placebo arms (at 24-36 weeks or 48-52 weeks) were examined according to the start date of each study in order to determine trends over time. Placebo group SRI-4 response rates in studies that met their primary endpoint were compared with those that did not. Results: Twenty-seven (14 phase II and 13 phase III) studies met the search criteria. Eleven of them met their primary endpoints. The study start dates ranged from Dec 2006 to Jan 2017. Mean/median total subject numbers were 461/349. Mean/median placebo subjects’ age at baseline were 39.9/39.2 and SLEDAI: 10.6/10.6. Mean/median placebo SRI-4 responses at Week 24-36 were 47.2%/45.8% and 42.8%/43% at Week 48-52. For BICLA, the rates were 40.3%/37.2% at Week 24-36 and 33.2%/33.5% at Week 48-52. As expected, lower placebo response was found in trials that met primary endpoints vs studies that did not (p=0.005). Total subject numbers and recruitment rates decreased over time while placebo SRI-4 response rates increased overall (Figure). However, there has been a greater range of placebo responses in more recent trials. Similar trends were observed in BICLA responses at Week 24-36 and 48-52, and in a corticosteroid reduction endpoint (percent of patients with reduction in steroid dose by ≥25% and to ≤7.5 mg/day prednisone/equivalent) at Week 48-52. Enrollment of patients from North America decreased while proportions of Eastern Europeans increased over time (Figure). Conclusion: High placebo response rates pose a continuing challenge in SLE studies and are associated with primary endpoint failures. Clinical trial metrics have been changing over time, with declining size and recruitment rates, possibly due to competition from increasing numbers of studies. These trends should be considered while designing and conducting future trials. Attention to site training and data quality may be particularly important to control high placebo rates, especially as trial sizes decrease. Figure. Disclosure of Interests: Ewa Olech Grant/research support from: BMS, Consultant of: Abbvie, Amgen, Remegen, Employee of: IQVIA, Speakers bureau: Abbvie, Amgen, Merck, Pfizer, UCB, Eduard van Rijen Employee of: IQVIA, Faizi Hussain Employee of: IQVIA, Gregory Dennis Employee of: IQVIA, Ali Ashrafzadeh Employee of: IQVIA, Joan T Merrill Grant/research support from: Xencor, Bristol Myers Squibb, Glaxo Smith Kline, Consultant of: Xencor, Abbvie, UCB, Glaxo Smith Kline, EMD Serono, Astellas, Remegen, Celgene/Bristol Myers Squibb, Exagen, Astra Zeneca, Amgen, Jannsen, Servier, ILTOO, Daitchi Sankyo, Lilly, Paid instructor for: Abbvie, Bristol Myers Squibb

Background Tofacitinib is an oral JAK inhibitor for the treatment of RA. In clinical practice, a proportion of patients (pts) with RA may not be candidates for treatment with the conventional synthetic DMARD (csDMARD) methotrexate (MTX).1 Objectives To evaluate tofacitinib 5 or 10 mg BID efficacy and safety using pooled data from 8 Phase (P) 2 and 6 P3 trials in RA pts who were (1) inadequate responders (IR)/intolerant to csDMARDs, but did not have an IR or intolerance to MTX or biologic DMARDs (ie, non-MTX csDMARD-IR population) or (2) pts with an IR/intolerance to any csDMARD including MTX but not bDMARD-IR (ie, 2nd-line population). Methods Month 3 efficacy outcomes included proportions of pts achieving ACR20/50/70 responses, and Disease Activity Score 28-4(ESR) (DAS28-4[ESR])<2.6 (remission), as well as change from baseline in DAS28-4(ESR) and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores. No multiplicity adjustments were made. Crude incidence rates (CIR; unique pts with events/100 pt-years) based on adverse event (AE) reporting through Month 24 were calculated for treatment-emergent AEs (TEAEs), serious AEs (SAEs), discontinuations (DCs) due to AEs and AEs of special interest. Results In the P2/3 tofacitinib RA trials, prior csDMARDs received by the non-MTX csDMARD-IR and 2nd-line populations, respectively were: chloroquine (17.7% and 37.2%), hydroxychloroquine (13.7% and 22.7%), leflunomide (19.4% and 20.9%), MTX (7.3% and 93.3%), sulfasalazine (31.1% and 27.1%) and others (8.0% and 11.1%); pts may have received >1 prior csDMARD. The non-MTX csDMARD-IR population included 208, 247 and 82 pts receiving tofacitinib 5 and 10 mg BID or placebo (PBO), respectively; the 2nd-line population comprised 1206, 1266 and 856 pts, respectively. Baseline characteristics were generally similar between populations except for mean RA duration (5.2–7.2 years, non-MTX csDMARD-IR pts; 8.2–8.5 years, 2nd-line pts). Most pts were female (80.3–85.4%), mean age range was 49.7–52.5 years and mean DAS28-4(ESR) score ranged from 6.2–6.5. Tofacitinib 5 and 10 mg BID achieved higher ACR responses and greater changes from baseline in DAS28-4(ESR) and HAQ-DI scores vs PBO at Month 3 in both populations (Table). Numerically higher proportions of non-MTX csDMARD-IR pts achieved efficacy outcomes vs 2nd-line population. CIRs for SAEs, DCs due to AEs and AEs of special interest were similar across groups; CIRs for TEAEs were higher with PBO vs tofacitinib. AE frequency was generally lower in the non-MTX csDMARD-IR population vs 2nd-line population. Conclusions This analysis indicates that tofacitinib is associated with similar efficacy and safety outcomes between csDMARD-IR (including MTX-IR) pts and those who are csDMARD-IR but not MTX-IR. This suggests a favourable tofacitinib benefit/risk profile for RA pts who have a contraindication to or refuse treatment with MTX and failed other csDMARDs. References Lopez-Olivo MA et al. Cochrane Database Syst Rev 2014; CD000957. Acknowledgements This study was sponsored by Pfizer Inc. Editorial support was provided by K Nicholson of CMC and was funded by Pfizer Inc. Disclosure of Interest J. Tesser Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, A. Gül Consultant for: AbbVie, Bristol-Myers Squibb, MSD, Novartis, Pfizer Inc, Roche, Servier, UCB, Xoma, E. Olech Grant/research support from: AbbVie, Amgen, Celgene, Genentech, Janssen, Regeneron, Sanofi-Aventis, UCB, Vertex Pharmaceuticals, Consultant for: AbbVie, Amgen, Celgene, Genentech, Janssen, Regeneron, Sanofi-Aventis, UCB, Vertex Pharmaceuticals, K. Oelke Grant/research support from: Novartis, Consultant for: Novartis, Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb, Pfizer Inc, Crescendo Biosciences, UCB, T. Lukic Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Murray Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Zhang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Takiya Shareholder of: Pfizer Inc, Consultant for: Pfizer Inc

BackgroundTwo global Phase III studies evaluated the safety and efficacy of subcutaneous tocilizumab (TCZ-SC). SUMMACTA was a 97-week study that compared TCZ-SC 162 mg every week (qw) with intravenous TCZ (TCZ-IV) 8 mg/kg every 4 weeks. At week 24, patients (pts) were re-randomized to remain on the initially assigned formulation or switch to the other formulation. BREVACTA was a 96-week study that compared TCZ-SC 162 mg every 2 weeks (q2w) with placebo. From week 12 onward, pts could escape to TCZ-SC qw if they had <20% improvement in both swollen joint count (SJC) and tender joint count (TJC). At week 24, pts were re-randomized to receive TCZ-SC q2w via 2 different devices.ObjectivesTo assess long-term safety and efficacy of TCZ-SC in US pts who completed the SUMMACTA or BREVACTA core studies.MethodsIn this open-label, single-arm, US-based, Phase IIIb study, pts who completed SUMMACTA and BREVACTA could enroll and continue to receive their dosage of TCZ-SC q2w or qw, or switch from TCZ-IV to TCZ-SC qw. Nonbiologic disease-modifying antirheumatic drugs in combination with TCZ-SC were permitted. The primary safety endpoint was the proportion of pts with serious adverse events (SAEs). Secondary endpoints included the proportions of pts with adverse events of special interest and pts who discontinued, incidence of laboratory abnormalities and efficacy assessments.ResultsOf 217 pts treated, 76.5% were female and mean age was 58.4 years. A total of 23 pts (10.6%) had ≥1 SAEs, for a rate of 14.7/100 pt-years (Table). The most common SAEs were infections (n=7, 3.2%). Eight pts had ≥1 serious or opportunistic infections or infections requiring IV anti-infectives. Thirty-four pts withdrew from TCZ-SC treatment, 13 (6.0%) due to AEs, 21 (9.7%) due to nonsafety reasons. Aminotransferase elevations were reported in 27.2% of pts but were not associated with liver toxicity. Neutropenia (5.1%) was transient. Injection site reactions occurred in 6 patients, were nonserious and resolved without sequelae. No anaphylaxis or deaths were reported. Mean Clinical Disease Activity Index and 28-joint Disease Activity Scores (DAS28) decreased from baseline and remained stable thereafter.ConclusionsThe safety of TCZ-SC during the long-term extension period of the SUMMACTA and BREVACTA studies was consistent with the safety profile established during the core studies, with no new safety signals identified. Mean efficacy improvements observed from baseline were stable over time. These results demonstrate the durability of the safety and efficacy responses with long-term exposure to TCZ-SC.Disclosure of InterestA. Kivitz Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Genentech, Janssen, Pfizer, UCB, Consultant for: BMS, Genentech, UCB, Speakers bureau: BMS, E. Olech Grant/research support from: Genentech, Consultant for: Genentech, M. Borofsky: None declared, J. Devenport Employee of: Genentech, J. Pei Employee of: Genentech, T. Wallace Employee of: Genentech, M. Michalska Employee of: Genentech

Background Certolizumab pegol (CZP) significantly improved signs and symptoms of RA in a diverse group of patients, including 37.6% who previously used a TNF inhibitor.1 Objectives To evaluate short-term non-contrast low-field MRI for predicting long-term efficacy of CZP in patients with moderate to severe active RA who failed at least one non-biologic or biologic DMARD. Methods In this 2-center open-label study, 20 adult RA pts with DAS > 4.4, on stable dose of MTX, received CZP 400 mg at week (wk) 0, 2 and 4, followed by 200 mg every two wks for 52 wks. All patients had unilateral hand and wrist non-contrast MRI using 0.2 T extremity unit at baseline, 6wk, 16wk and 52wk. The images were scored according to the RAMRIS system and 9-point cartilage loss (CL) scale by a radiologist blinded to visit order. Results Baseline patients’ characteristics were as follows: Mean (SD) age 52.2 (16.9) years old, 70% female, Mean (SD) disease duration 7.3 (5.6) years, 50 % of pts were RF+, 60% anti-CCP+. Mean (SD) MTX dose was 17.25 (3.0) mg/week, Prednisone 2.5 (5.0) mg, 85% of pts were previously on a biologic. Tender/Swollen Joint Count (out of 68/66) was 34/16. Mean (SD) HAQ 4.38 (1.68), DAS28 6.60 (1.06), DAS28CRP 5.74 (0.66). 16/20 pts completed 52 wks. No serious adverse events were reported in this patient population. DAS28 and RAPID scores were significantly reduced at wks: 6, 12, 16, 24, 40, 48 and 52 compared with baseline (Wilcoxon; p<0.001). ACR20/50/70 response rates at 16 & 52 wks (with non-completers considered as non-responders) were 60/30/15 & 45/30/20 %, respectively. At wk 12, 80% and at wk 52, 69% of pts achieved moderate or good EULAR response. Only two pts achieved low disease activity (DAS<3.2) at wk 52. 80% of patients had a DAS28 improvement of ≥ 1.2 by week 12. Of these, 25% did not achieve EULAR response at wk 52. None of the remaining 20% of pts with DAS28 improvement < 1.2 by wk 12, had a EULAR response at wk 52. 52-wk EULAR responders had significantly higher improvement in the OST scores at 16 wks, as compared to non-responders (p= 0.043). Changes in SYN, ERO or CL scores did not differ substantially between the two groups (Figure 1). All pts who improved their OST scores by wk 16, were clinical responders at wks 12 and 52. 12-wk clinical responders had 73% probability of EULAR response at wk 52, but if they also had 16-wk OST improvement, the probability was 100% (PPV=1.0). Conversely, if OST worsened, the probability of achieving EULAR response at 52 wks was only 33% (NPV = 0.66). Image/graph Conclusions In this preliminary study of an active RA population who failed at least one DMARD and included 85% of pts who previously used a biologic, improvement of osteitis on MRI predicted long-term clinical response to CZP. This finding may be particularly significant in determining therapeutic choices in patients with RA who have previously used a biologic. Our observations were based on a small patient population and suggest a trend without statistical relevance. Larger studies should be done to confirm these findings. References Weinblatt ME, et al. Rheumatol. 2012; Østergaard M, et al. J Rheumatol. 2003; Peterfy C, et al. Arthritis Res Ther. 2012 Disclosure of Interest E. Olech Grant/research support from: Abbvie, Genentech, Pfizer, UCB, Vertex, Consultant for: Abbvie, Janssen, Pfizer, UCB, Speakers bureau: Abbvie, UCB, C. Peterfy Shareholder of: Spire Sciences, LLC, Grant/research support from: Amgen, Centocor / Janssen, Pfizer / Wyeth, Abbott, Roche, Genentech, Bayer, Consultant for: Abbott, Articulinx, Merck/ Schering-Plough, Roche, UCB, Pfizer / Wyeth, AstraZeneca, Bristol Myers-Squibb, BioClinica, Celgene, Genentech, Icon Medical Imaging, Lilly, Medimmune, Moximed, Novartis, Perceptive Informatics, VirtualScopics, Jannsen, Genzyme/Sanofi, Biogen-Idec, Employee of: Spire Sciences, LLC, J. DiCarlo Consultant for: Abbott, Amgen, AstraZeneca, BioClinica, Biogen-Idec, Bristol-Myers Squibb, Celgene, Centocor, Core Lab Partners, Crescendo, Eli Lilly, Genentech, Genzyme, Icon Medical Imaging, Johnson & Johnson, Merck, Novartis, Perceptive Informatics, Pfizer, Rigel, Roche, Sanofi, Samsung, UCB, VirtualScopics, Wyeth, Employee of: Spire Sciences, LLC, J. Sagliani: None Declared, A. Genovese: None Declared, N. Gaylis Grant/research support from: Genentech Roche, BMS, UCB, Consultant for: UCB, Speakers bureau: Janssen, UCB

Background: Inflammatory back pain (IBP) is an early feature of ankylosing spondylitis (AS) and its detection offers the prospect of early diagnosis of AS. However, since back pain is very common but only a very small minority of back pain sufferers have ASpA or AS, screening of back pain sufferers for AS is problematic. In early disease radiographs are often normal so that fulfilment of diagnostic criteria for AS is impossible though a diagnosis of axial SpA can be made if MRI evidence of sacroiliitis is present. This pilot study was designed to indicate whether a cost-effective pick up rate for ASpA/early AS could be achieved by identifying adults with IBP stratified on the basis of age. Methods: Patients aged between 18 and 45 years who were referred to a hospital physiotherapy service with back pain of more than 3 months duration were assessed for IBP. All were asked to complete a questionnaire based on the Berlin IBP criteria. Those who fulfilled IBP criteria were also asked to complete a second short questionnaire enquiring about SpA comorbidities, to have a blood test for HLA-B27 and CRP level and to undergo an MRI scan of the sacroiliac joints. This was a limited scan, using STIR, diffusion-weighted, T1 and T2 sequences of the sacroiliac joints to minimize time in the scanner and cost. The study was funded by a research grant from Abbott Laboratories Ltd. Results: 50 sequential patients agreed to participate in the study and completed the IBP questionnaire. Of these 27 (54%) fulfilled criteria for IBP. Of these, 2 patients reported a history of an SpA comorbidity - 1 psoriasis; 1 ulcerative colitis - and 3 reported a family history of an SpA comorbidity - 2 psoriasis; 1 Crohn’s disease. 4 were HLA-B27 positive, though results were not available for 7. Two patients had marginally raised CRP levels (6, 10 -NR ≤ 5). 19 agreed to undergo MRI scanning of the sacroiliac joints and lumbar spine; 4 scans were abnormal, showing evidence of bilateral sacroiliitis on STIR sequences. In all cases the changes met ASAS criteria but were limited. Of these 4 patients 3 were HLA-B27 positive but none gave a personal or family history of an SpA-associated comorbidity and all had normal CRP levels. Conclusions: This was a pilot study yielding only limited conclusions. However, it is clear that: Screening of patients referred for physiotherapy for IBP is straightforward, inexpensive and quick. It appears that IBP is more prevalent in young adults than overall population data suggest so that targeting this population may be efficient. IBP questionnaires could be administered routinely during a physiotherapy assessment. HLA-B27 testing in this group of patients with IBP is a suitable screening tool. The sacroiliac joint changes identified were mild and their prognostic significance is not yet clear so that the value of early screening needs further evaluation. Disclosure statement: C.H. received research funding for this study from Abbott. A.K. received research funding for this study, and speaker and consultancy fees, from Abbott. All other authors have declared no conflicts of interest.

Fibromyalgia (FM) is a chronic pain disorder of unknown etiology characterized by wide variability in symptom presentation, including pain, sleep, and cognitive symptoms. Additionally, many persons with FM suffer from comorbid depression, which may increase symptom severity and negatively impact treatment in comparison to FM patients without depression. Given the relationship between affect and pain, such that positive affect inhibits pain and negative affect enhances it, it is hypothesized that FM patients with depression would show differential modulation of pain and nociception compared with FM patients without depression. For the present study, FM patients who met American College of Rheumatology fibromyalgia criteria and who had physician-verified diagnoses were recruited and administered the Center for Epidemiologic Studies-Depression Scale (CES-D). Depression status was defined by CES-D ≥19 (n=5 FM+depression, n=5 FM w/o depression). Pain modulation was examined using a well-validated procedure called the Emotional Controls of Nociception (ECON) paradigm. Specifically, participants viewed pictures of varying emotional contents (mutilation, neutral, erotica) while suprathreshold electrocutaneous stimulations were delivered to the sural nerve of the ankle to elicit pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception). Prior research has shown that pain and NFR are reliably increased during mutilation pictures and decreased during erotic pictures. Results from the current study indicated that NFR was modulated in the FM without depression group, but not the FM+depression group. By contrast, pain was not modulated in either group; but, the FM+depression group rated the noxious stimulations as more painful than the no depression group. These findings suggest FM is generally associated with a disruption of supraspinal modulation of pain, whereas FM patients with depression also exhibit a disruption in cerebrospinal modulation of spinal nociception. Thus, the pathophysiology of pain may differ between these two subgroups of FM. Fibromyalgia (FM) is a chronic pain disorder of unknown etiology characterized by wide variability in symptom presentation, including pain, sleep, and cognitive symptoms. Additionally, many persons with FM suffer from comorbid depression, which may increase symptom severity and negatively impact treatment in comparison to FM patients without depression. Given the relationship between affect and pain, such that positive affect inhibits pain and negative affect enhances it, it is hypothesized that FM patients with depression would show differential modulation of pain and nociception compared with FM patients without depression. For the present study, FM patients who met American College of Rheumatology fibromyalgia criteria and who had physician-verified diagnoses were recruited and administered the Center for Epidemiologic Studies-Depression Scale (CES-D). Depression status was defined by CES-D ≥19 (n=5 FM+depression, n=5 FM w/o depression). Pain modulation was examined using a well-validated procedure called the Emotional Controls of Nociception (ECON) paradigm. Specifically, participants viewed pictures of varying emotional contents (mutilation, neutral, erotica) while suprathreshold electrocutaneous stimulations were delivered to the sural nerve of the ankle to elicit pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception). Prior research has shown that pain and NFR are reliably increased during mutilation pictures and decreased during erotic pictures. Results from the current study indicated that NFR was modulated in the FM without depression group, but not the FM+depression group. By contrast, pain was not modulated in either group; but, the FM+depression group rated the noxious stimulations as more painful than the no depression group. These findings suggest FM is generally associated with a disruption of supraspinal modulation of pain, whereas FM patients with depression also exhibit a disruption in cerebrospinal modulation of spinal nociception. Thus, the pathophysiology of pain may differ between these two subgroups of FM.

The American College of Rheumatology Extremity Magnetic Resonance Imaging Task Force has provided a timely focus on the growing importance of magnetic resonance imaging (MRI) for rheumatologists (1). The report of the task force identifies many of the key publications in this area and emphasizes the need for more research to advance the utility of this tool. The report provides clear descriptions of terminology and distinguishes between high-field extremity scanners ( 1.0T), to which most currently published MRI literature would apply, and the low-field (0.2T) extremity scanners. We wish to expand on some of the points raised by the task force and support the call for further research. That MRI provides superior assessment of structural damage in rheumatoid arthritis (RA) comes as no surprise. What is surprising, as the task force notes, is how little rheumatologists have used this technology to benefit their patients. Are rheumatologists less aggressive adopters of technological innovation than their medical colleagues? At least part of the answer stems from the fact that, until very recently, rheumatologists had little ability to prevent the progression of structural damage in RA. Without this capability, information about joint structure on the level that MRI can provide wasn’t needed for management of RA. The introduction of tumor necrosis factor inhibition and recognition of the benefits of early intervention shifted the focus from controlling pain to early, intensive treatment to prevent irreversible functional disability. Implementation, however, is not straightforward, since a significant proportion of patients with early RA do not have rapid structural progression (2,3). Treating all cases of RA with biologic agents would incur excessive costs and unnecessary risks. Determining which newly presenting patients have the potential for progression has therefore become an important concern, creating a new demand for imaging to detect the earliest evidence of structural damage and features predicting erosion. MRI offers a unique solution. Not only has it been shown to detect bone erosions more sensitively and earlier than radiography, but it can also be used to visualize pre-erosive inflammation in synovium and bone (4,5). This has led to increasing use of MRI in RA clinical research and to the emergence of specialized MRI systems specifically designed for office-based rheumatology practice. These low-field extremity MRI units provide images of the hands and feet at a fraction of the cost and inconvenience of conventional 1.5T whole-body MRI. The question is whether the low-field MRI systems still offer a substantial advantage over conventional radiography for diagnosing and/or monitoring erosive disease in RA. Although the volume of data on low-field extremity MRI is less than that available on high-field MRI, published data show a high correlation between results obtained with these systems with respect to erosion detection. In direct comparisons, low-field extremity MRI showed approximately twice the sensitivity of radiography for detecting erosions (6). With regard to progression of disease, a recent study demonstrated that low-field MRI of a single wrist and the second through the fifth metacarpophalangeal joints was more sensitive to change than were standard radiographs of both hands, wrists, and feet (7). We therefore believe that there would be a great deal to be gained by rheumatologists and their patients if extremity MRI were to be assimilated into routine clinical practice.

Deficiency of dehydroepiandrosterone (DHEA) is associated with lupus erythematosus, diabetes mellitus, Alzheimer disease, and some cancers, but we are not yet ready to conclude that prescribing supplemental DHEA is helpful in these or any other conditions. DHEA shows some promise in observational clinical studies and laboratory experiments, but we still need large-scale human studies to answer key questions. For now, we do not have enough evidence to recommend routine treatment with DHEA. As with other supplements, quality control is always a concern, and different brands may contain different amounts of active ingredient.