Objectives: Biologic disease-modifying antirheumatic drugs (bDMARDs) are prescribed sequentially in the treatment of rheumatoid arthritis (RA). Healthcare decision makers continue to debate their use, mainly because of their high costs. Our aim was to perform an economic evaluation for France of bDMARD sequences for treatment of moderate-to-severe RA after inadequate response or intolerance to conventional DMARDs (eg, methotrexate). Methods: A discretely integrated condition event simulation was developed to track the course of patients from first bDMARD through switches to further lines in a sequence. The model included 11 events, 91 conditions, and 21 controlling equations. Inputs were obtained from a meta-analysis of clinical trials, a French registry, national drug lists, and databases. Survival, time with minimal activity, quality-adjusted life-years (QALYs), and total costs were output. Structural and probabilistic sensitivity analyses were conducted. Results: Sequences starting with etanercept biosimilars (ETB) cost less, with ETB-abatacept-infliximab the least expensive: the mean lifetime discounted total cost was (sic)116 912 per patient, with a mean of 11.166 QALYs. Most other strategies were dominated or led to small QALY gains (0.0008-0.0329). Only ETB-tocilizumab-abatacept made it onto the efficiency frontier, but at (sic)955 778 per QALY gained. These results were confirmed in several scenarios and uncertainty analyses. Conclusion: Given minor differences in QALYs gained between bDMARD sequences with large cost differences, starting with biosimilars was more efficient than starting with branded products. Our model and findings should provide French and other decision makers with useful tools to address the challenges of comparing sequences of treatments for RA.

OBJECTIVES:The aim of this study was to estimate the effectiveness of first-line biologic disease modifying drugs(boDMARDs), and their approved biosimilars (bsDMARDs), compared with conventional (csDMARD) treatment, in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses. METHODS:Systematic literature search, on eight databases to January 2017, sought ACR and EULAR data from randomized controlled trials (RCTs) of boDMARDs / bsDMARDs (in combination with csDMARDs, or monotherapy). Two adult populations: methotrexate (MTX)-naïve patients with severe active RA; and csDMARD-experienced patients with moderate-to-severe active RA. Network meta-analyses (NMA) were conducted using a Bayesian Markov chain Monte Carlo simulation using a random effects model with a probit link function for ordered categorical. RESULTS:Forty-six RCTs met the eligibility criteria. In the MTX-naïve severe active RA population, no biosimilar trials meeting the inclusion criteria were identified. MTX plus methylprednisolone (MP) was most likely to achieve the best ACR response. There was insufficient evidence that combination boDMARDs was superior to intensive (two or more) csDMARDs. In the csDMARD-experienced, moderate-to-severe RA population, the greatest effects for ACR responses were associated with tocilizumab (TCZ) monotherapy, and combination therapy (plus MTX) with bsDMARD etanercept (ETN) SB4, boDMARD ETN and TCZ. These treatments also had the greatest effects on EULAR responses. No clear differences were found between the boDMARDs and their bsDMARDs. CONCLUSIONS:In MTX-naïve patients, there was insufficient evidence that combination boDMARDs was superior to two or more csDMARDs. In csDMARD-experienced patients, boDMARDs and bsDMARDs were comparable and all combination boDMARDs / bsDMARDs were superior to single csDMARD.

To evaluate the prevalence of baseline abnormalities in standard laboratory tests in patients with early arthritis and their impact on selection of disease-modifying antirheumatic drugs according to American College of Rheumatology (ACR) recommendations and/or of nonsteroidal anti-inflammatory drugs.In three cohorts of patients with early arthritis (the ESPOIR, VErA, and Brittany cohorts), we evaluated the prevalence of anemia (hemoglobin <1 3 g/dL in men and 12 g/dL in women), leukopenia (<3500 per mm(3)), thrombocytopenia (<150000 per mm(3)), renal dysfunction (mild, creatinine clearance [CrCl]=60-89.9 mL/min; moderate, CrCl=30-59.9 mL/min; or severe, CrCl<30 mL/min), liver cytolysis (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]>N or>2N), and systemic inflammation (erythrocyte sedimentation rate [ESR]>20 and C-reactive protein [CRP]>6).We evaluated 1393 patients (1018 women and 375 men). Anemia was present in 363/1366 (26.5%) patients, leukopenia in 18/1372 (1.3%), and thrombocytopenia in 13/1371 (0.9%). ESR elevation was seen in 50.4% of patients and CRP elevation in 62.7%. The level of AST was above normal in 4% and of ALT in 10% of patients. No patient had severe renal dysfunction, 5.6% had moderate renal dysfunction, and 42.6% had mild renal dysfunction. Among the 1094 patients who had undergone all the tests, only 18 (1.64%, 95% confidence interval, 1-2.64) had a formal contraindication to methotrexate therapy according to ACR recommendations (4 had leukopenia, 12 had high ALT levels, and 2 had high ALT and AST levels).Patients with recent-onset arthritis often have anemia, mild or moderate renal dysfunction, and abnormal liver function. However, fewer than 2% have laboratory test abnormalities contraindicating methotrexate therapy.

Objective: To evaluate the prevalence of baseline abnormalities in standard laboratory tests in patients with early arthritis and their impact on selection of disease-modifying antirheumatic drugs according to American College of Rheumatology (ACR) recommendations and/or of nonsteroidal anti-inflammatory drugs. Methods: In three cohorts of patients with early arthritis (the ESPOIR, VErA, and Brittany cohorts), we evaluated the prevalence of anemia (hemoglobin < 13 g/dL in men and 12 g/dL in women), leukopenia ( < 3500 per mm(3)), thrombocytopenia ( < 150 000 per mm(3)), renal dysfunction (mild, creatinine clearance [CrCl] = 60-89.9 mL/min; moderate, CrCl = 30-59.9 mL/min; or severe, CrCl < 30 mL/min), liver cytolysis (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] > N or > 2N), and systemic inflammation (erythrocyte sedimentation rate [ESR] > 20 and C-reactive protein [CRP] > 6). Results: We evaluated 1393 patients (1018 women and 375 men). Anemia was present in 363/1366 (26.5%) patients, leukopenia in 18/1372 (1.3%), and thrombocytopenia in 13/1371 (0.9%). ESR elevation was seen in 50.4% of patients and CRP elevation in 62.7%. The level of AST was above normal in 4% and of ALT in 10% of patients. No patient had severe renal dysfunction, 5.6% had moderate renal dysfunction, and 42.6% had mild renal dysfunction. Among the 1094 patients who had undergone all the tests, only 18 (1.64%, 95% confidence interval, 1-2.64) had a formal contraindication to methotrexate therapy according to ACR recommendations (4 had leukopenia, 12 had high ALT levels, and 2 had high ALT and AST levels). Conclusion: Patients with recent-onset arthritis often have anemia, mild or moderate renal dysfunction, and abnormal liver function. However, fewer than 2% have laboratory test abnormalities contraindicating methotrexate therapy. (C) 2013 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 42:474-481

Objective.To evaluate the usefulness of the polymyalgia rheumatica (PMR) activity score (PMR-AS) in guiding adjustment of glucocorticoid (GC) dosage.Methods.Rheumatologists prospectively included patients receiving GC therapy for PMR. At each visit, they assessed disease activity using a visual analog scale for physician’s global assessment (VASph) and recorded whether a flare was diagnosed and/or the GC dosage was changed. In each patient, the PMR-AS was calculated using the formula of Leeb and Bird: C-reactive protein (mg/dl) + VAS pain score (0 to 10) + VASph (0 to 10) + (morning stiffness in min × 0.1) + elevation of upper limbs (0–3). We evaluated the correlation between PMR-AS and GC dosage changes in the group already treated with GC.Results.We included 89 patients (mean age 74.6 ± 6.2 yrs; disease duration 1.6 ± 2.2 yrs), who had a total of 149 visits. PMR-AS was available for 137 visits. Of those, 124 involved patients already treated with GC, and 13 patients who started GC treatment. The Spearman correlation coefficient between PMR-AS values and GC dosage change was 0.58 (p < 0.001). In the group already treated with GC, when the PMR-AS was higher than 20, GC dosages were never decreased. When the PMR-AS was between 10 and 20, GC dosages were decreased in 4 patients, unchanged in 4, and increased by < 5 mg in 4 patients. When PMR-AS was < 10, GC dosages were generally decreased.Conclusion.The PMR-AS is helpful for diagnosing flares of PMR and may also assist in everyday practice to decide how to change the GC dosage.

Background The BSR recommends for the diagnosis and management of polymyalgia rheumatica (PMR) blood cells count, blood electrolytes and renal function, liver function, bone metabolism tests, thyroid hormones, muscle enzymes, rheumatoid serology, plasma proteins electrophoresis, erythrocyte sedimentation rate and C-reactive protein, chest X-ray and urine analysis (1). Objectives To conduct a practice survey of laboratory and imaging studies used by French physicians (rheumatology or internal medicine) to diagnose PMR. Methods 101 rheumatologists or internal medicine physicians (74 in western region and a random sample of 27 in other regions) were asked 1- to recruit one patient with PMR and to record laboratory and imaging studies performed and 2- answer to a questionnaire describing a paper-case of PMR. Results were analysed in the overall group and in clinical presentation subgroups [typical, atypical PMR (fatigue, weight loss, fever, synovitis and swelling of the dorsal hand) and associated to giant cell arteritis]. To simplify the reporting of results, we divided the investigations into four groups based on whether they were obtained in 0% to 24%, 25% to 49%, 50% to 74%, or 75% to 100%) of patients. Results 101 physicians responded to the questionnaire and included one patient (mean age 74.3yrs, 19% had fever, 13% clinical signs of GCA, 12% synovitis and 4% hand dorsal edema). Investigations done in more than 50% of the 101 patients (recruited patients or paper-case) were blood cell count and platelets; kidney and liver function test; bone metabolism (calcium, phosphorus and vitamin D); protein serum electrophoresis; creatine phosphokinase, rheumatoid factors and ACPA, X-Rays (shoulders, pelvis, hands, feet, chest). No differences were found between investigations in patients with typical PMR and the remainder excepted hand X-rays (for synovitis), CT-Scan, echocardiography, ANCA, urine and hemocultures (for fever), and temporal artery biopsy (for suspicion of Giant cell arteritis). Conclusions Although considerable variability occurred, this study suggests that a limited panel of laboratory and imaging studies (close to the BSR recommendation) is recommended by at least 50% of the physicians to the patients with PMR in France. References Dasgupta B, Borg FA, Hassan N, Barraclough K, Bourke B, Fulcher J, et al. BSR and BHPR guidelines for the management of polymyalgia rheumatica. Rheumatology (Oxford). 2010;49(1):186–90. Disclosure of Interest None Declared

STUDY DESIGN:Case report. OBJECTIVE:To illustrate the usefulness of broad-range bacterial polymerase-chain-reaction (PCR) testing in osteoarticular infections by Capnocytophaga canimorsus. SUMMARY OF BACKGROUND DATA:C. canimorsus is a gram-negative bacillus that was first identified in 1976. It is a normal inhabitant of the oral mucosa of dogs (26%) and cats (15%). The main clinical patterns are septicemia, which may cause fatal septic shock (in 30% of cases) but arthritis and discitis are possible. C. canimorsus is susceptible to many antimicrobials including β-lactam antibiotics. METHODS:About a case report of 54-year-old man transferred to our institution for discitis, we discuss about PCR for C. canimorsus discitis diagnosis. RESULTS:At admission, the only abnormal physical finding was global pain and stiffness of the lumbar spine. Radiographs of the lumbar spine and pelvis showed lumbar spondylosis, degenerative disc disease, and previously known degenerative facet joint disease. Magnetic resonance imaging indicated L3-L4 discitis with damage to both vertebrae and adjacent discs. Findings were negative from blood and urine cultures, serological tests for the HIV and brucellosis, and sputum tests for Mycobacterium tuberculosis. A percutaneous biopsy of the L3-L4 disc was performed but the bacteriological studies recovered no organisms. A second needle biopsy was performed for broad-range 16S rDNA PCR testing, which identified C. canimorsus. CONCLUSION:Broad-range PCR provided the microbiological diagnosis of culture-negative discitis in our patient. Broad-range PCR should be considered in patients with culture-negative osteoarticular infections.

Objective: To evaluate the validity and reliability of the polymyalgia rheumatica (PMR) activity score (PMR-AS) for relapse diagnosis by general practitioners (GPs) who manage a large proportion of patients with PMR.Methods: Seven clinical vignettes of PMR were used, for which 35 rheumatologists previously made a diagnosis of relapse or no relapse with greater than 80% agreement. These vignettes were submitted to 163 GPs, who were asked to assess disease activity using a visual analogue scale (VASph), this being the only physician-dependent component of the PMR-AS. The 1116 available vignette GP combinations were used to assess differences in VASph assessed by GPs versus rheumatologists. Statistical associations linking a relapse diagnosis by the rheumatologists ( the reference standard) to the value of the GP-assessed PMR-AS or its components (GP-assessed VASph, visual analogue scale pain score, C-reactive protein, morning stiffness and elevation of upper limbs) were evaluated.Results: No significant differences were found between VASph scores by GPs versus rheumatologists for any of the vignettes. A relapse diagnosis was strongly associated with PMR-AS values of 7 or more ( sensitivity 99.4%; specificity 93.3%; agreement 95.9% (95% CI 94.5% to 97.0%) with kappa = 0.92). Of the 590 GP-vignette combinations with PMR-AS values lower than 7, all but three (0.5%) had no relapse diagnosis. Of 510 combinations with PMR-AS values of 7 or more, only 42 (8%) had no flare diagnosis.Conclusions: This study supports the validity of the PMR-AS in primary care practice and provides evidence that a good scoring system can be useful to guide clinical and therapeutic decisions.

The diagnosis of inflammatory bowel disease (IBD) based on a cluster of clinical and biological arguments includes two steps. First, IBD have to be distinguished from other digestive diseases, and then, it is important to separate among the major forms of IBD: Crohn's disease (CD) from ulcerative colitis (UC). The aim of this study was to compare different autoantibodies (Ab) in an unselected population of 38 undeterminated colitis diagnosis including CD patients (N=10) and UC patients (N=13) for whom the diagnosis was established a posteriori. According to our results, antilactoferrin (LF) Abs exist in 56.5% of the maladie inflammatoire chronique de l'intestin (MICI) but the specificity of such a test is moderate (66.7%). When IBD is established, anti-Saccharomyce cerevisiae Abs, on one hand, and anti-perinuclear neutrophil cytoplasmic Abs (p-ANCA), on the other hand, allowed to discriminate between CD and UC, respectively, but sensibility for both tests are moderate (<= 30%). On the whole, anti-LF, ASCA and p-ANCA may help to make earlier diagnosis of CD or UC. (C) 2008 Elsevier Masson SAS. All rights reserved.

OBJECTIVETo evaluate the effectiveness of the polymyalgia rheumatica activity score (PMR-AS) in diagnosing disease flares.METHODSRheumatologists prospectively included 89 patients with PMR (mean +/- SD age 74.6 +/- 6.2 years, mean +/- SD disease duration 1.6 +/- 2.2 years). At each visit, the rheumatologist assessed disease activity using a visual analog scale (VAS) and recorded whether a disease flare was diagnosed and/or the glucocorticoid dose changed. Overall, 137 visits including 49 pairs (allowing intraindividual comparisons) were available; a disease flare was diagnosed at 32 visits. We evaluated statistical associations linking flare diagnosis to the PMR-AS, each of its components (VAS, VAS for pain, C-reactive protein, morning stiffness, and elevation of upper limbs), and changes in these parameters between 2 visits.RESULTSAssociations with disease flare diagnosis were strongest for PMR-AS scores > or =9.35 (agreement 92%, 95% confidence interval [95% CI] 85.8-95.7%, kappa = 0.78; sensitivity 96.6%, 95% CI 80.4-99.8; specificity 90.7%, 95% CI 83.2-95.2) and for DeltaPMR-AS scores > or =6.6 (agreement 98%, 95% CI 88.0-99.9%, kappa = 0.95; sensitivity 100%, 95% CI 74.7-100; specificity 97.1%, 95% CI 82.9-99.8). Other parameters showed weaker diagnostic performance.CONCLUSIONThis study supplies new evidence that the PMR-AS is useful for monitoring PMR activity in everyday practice and for managing glucocorticoid tapering. PMR activity changes seem even more relevant than absolute values.

Objective: To evaluate the relevance of the blood B-cell subset profile for the diagnosis of Sjögren syndrome. Methods: The distribution of mature blood B cells from Bm1 through Bm5 was determined in 161 patients, of whom 25 fulfilled the American–European Consensus Group criteria for primary SS (pSS), and 136 served as disease controls. Results: The percentage of Bm2 and Bm2′ cells was increased in the patients with pSS compared with 54 patients with rheumatoid arthritis (RA) and 18 with systemic lupus erythematosus (SLE) (p<0.001 for the two comparisons). In contrast, those of early Bm5 (eBm5) and Bm5 were decreased in patients with pSS, compared with patients with RA and with SLE (p<0.001 for the two comparisons). The receiver operating characteristic curves allowed for an optimising cut-off value of Bm2+Bm2′ cells at 71.1% for 88.0% sensitivity and 83.1% specificity, that of eBm5+Bm5 cells at ⩽13.5% for 84.0% sensitivity and 83.1% specificity, and, consequently, that of Bm2+Bm2′/eBm5+Bm5 at ⩾5 for 88.0% sensitivity and 84.6% specificity. Conclusion: Given its presentation as a signature for pSS, relative to RA and SLE, such a distribution of B-cell subsets might provide a useful diagnostic tool.

Letters7 October 2008Right-Sided Native Valve Endocarditis Revealing Adult-Onset Still DiseaseAlain Saraux, MD, PhD, Aymeric Binard, MD, Valérie Devauchelle-Pensec, MD, PhD, Yannick Jobic, MD, and Sandrine Jousse-Joulin, MDAlain Saraux, MD, PhDFrom Brest Teaching Hospital, 29609 Brest, France.Search for more papers by this author, Aymeric Binard, MDFrom Brest Teaching Hospital, 29609 Brest, France.Search for more papers by this author, Valérie Devauchelle-Pensec, MD, PhDFrom Brest Teaching Hospital, 29609 Brest, France.Search for more papers by this author, Yannick Jobic, MDFrom Brest Teaching Hospital, 29609 Brest, France.Search for more papers by this author, and Sandrine Jousse-Joulin, MDFrom Brest Teaching Hospital, 29609 Brest, France.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-149-7-200810070-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: Adult-onset Still disease (AOSD) can manifest as noninfective endocarditis that simulates infective endocarditis. It is the most common connective tissue disease responsible for fever of unknown origin (1).Objective: To report a case of noninfective endocarditis of the tricuspid valve caused by AOSD in a patient with fever of unknown origin.Case Report: A 17-year-old man was transferred to our institution for evaluation of fever of unknown origin. His symptoms had started a few weeks earlier and consisted of high-grade fever (temperature up to 39 °C), asthenia, myalgia, night sweats, intermittent sore throat, knee pain, and headache. At admission, ...References1. Cunha BA. Fever of unknown origin: focused diagnostic approach based on clinical clues from the history, physical examination, and laboratory tests. Infect Dis Clin North Am. 2007;21:1137-87, xi. [PMID: 18061092] CrossrefMedlineGoogle Scholar2. Fautrel B, Zing E, Golmard JL, Le Moel G, Bissery A, Rioux C; et al.. Proposal for a new set of classification criteria for adult-onset still disease. Medicine (Baltimore). 2002;81:194-200. [PMID: 11997716] CrossrefMedlineGoogle Scholar3. Moreillon P, Que YA. Infective endocarditis. Lancet. 2004;363:139-49. [PMID: 14726169] CrossrefMedlineGoogle Scholar4. Churchill MA, Geraci JE, Hunder GG. Musculoskeletal manifestations of bacterial endocarditis. Ann Intern Med. 1977;87:754-9. [PMID: 145198] LinkGoogle Scholar5. Roldan CA, Shively BK, Crawford MH. An echocardiographic study of valvular heart disease associated with systemic lupus erythematosus. N Engl J Med. 1996;335:1424-30. [PMID: 8875919] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Brest Teaching Hospital, 29609 Brest, France.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAutoinflammation leading to autoimmunity in adult-onset Still’s disease: more than simple coincidence?Les endocardites non infectieusesVégétation tricuspidienne au cours d’une maladie de Still, une manifestation non infectieuse rare de lésion intracardiaqueEndocarditis in Adult-onset Still Disease: A Case Report and Literature ReviewAdult-Onset Still's Disease and Cardiac Tamponade: A Rare AssociationAtteinte cardiorespiratoire au cours de la maladie de Still de l’adulteA Rare Presentation of Endocarditis in Adult-onset Still’s Disease in Diagnosis of Fever of Unknown Origin: Table 1. 7 October 2008Volume 149, Issue 7Page: 517-519KeywordsEchocardiographyEndocarditisFever of unknown originFeversInflammationKneesLaboratory testsMyalgiaSystoleThorax ePublished: 7 October 2008 Issue Published: 7 October 2008 Copyright & PermissionsCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

Given the prominent role currently assigned to B lymphocytes in systemic lupus erythematosus, it is not surprising that the B cell activity factor belonging to the tumor necrosis factor family (BAFF) is involved in its pathogenesis. This cytokine is produced in excess, and inserted into its receptors on the surface of circulating B cells. Up-regulation of BAFF is most likely to lead to breach of tolerance by aberrant survival of B cells directed to the self. Trials aimed at blocking BAFF have thus been set out. Yet the results are awaited.

Un dolor dorsal es un síntoma simple y frecuente que a menudo se relaciona con una causa funcional. Sin embargo, existen múltiples trampas diagnósticas como, por ejemplo, los dolores referidos de origen visceral. El procedimiento clínico debe ser minucioso para descartar las causas graves de dorsalgia sintomática (infecciones, tumores) y determinar con certeza el origen osteoarticular de los dolores. A continuación deben descartarse las causas mecánicas e inflamatorias, para poder formular entonces el diagnóstico de certeza de dorsalgia funcional.

Be they follicular cells within the germinal centers (GCs) or marginal zone (MZ), all naïve mature B lymphocytes need tonic signaling to stay alive. We reasoned that the same holds true for those B lymphocytes that proliferate in the salivary glands (SGs) of patients with primary Sjögren’s syndrome. Based on B cell infiltration, 11 SGs and three tonsil samples were selected for further examination. Tissue sections were stained using CD20 combined with CD10, CD21, CD27, CD38 or IgD. They were also laser-microdissected for quantitative RT-PCR of transcription factors, GC-specific activation-induced cytidine deaminase (AID) and TLR9. Some B cell aggregates proved to be real GCs according to their membrane markers, whereas others were clusters of transitional type II B cells. These contained mRNAs for Notch-2 and Blimp-1, but not for Pax-5, Bcl-6 and AID. Unanticipated was the finding of mRNAs for TLR9 in these clusters of MZ B-cells, but not in the real GCs. Not only do TLR9 deliver sufficiency of tonic signaling to keep B cells alive, but they also confer autoreactive B cells with an MZ-like phenotype. Thus, TLRs might be targets for forthcoming biotherapies.

OBJECTIVE:To evaluate associations linking glucocorticoid dose changes in patients with polymyalgia rheumatica (PMR) to the PMR activity score (PMR-AS) and its components.METHODS:Nine clinical vignettes of PMR were written by a panel of experts and submitted to 35 rheumatologists, who were asked to assess disease activity using a visual analog scale (VASph) and to determine whether there was a relapse of PMR requiring an increase in the glucocorticoid dose. In 7 vignettes, >80% of the rheumatologists agreed on the diagnosis of relapse justifying the glucocorticoid dose decision. A total of 243 vignette-physician combinations were obtained. Using these vignettes, we evaluated statistical associations linking a decision to increase the glucocorticoid dose to the value of PMR-AS, of its components (VASph, visual analog scale for pain [VASp], C-reactive protein level [CRP], morning stiffness [MST], and elevation of upper limbs [EUL]), or to the difference in these variables between the last 2 visits (dPMR-AS, dVASph, dVASp, dCRP, dMST, and dEUL).RESULTS:The strongest associations with a decision to increase the glucocorticoid dose occurred with dPMR-AS >4.2, dMST >10 minutes, dVASph >1.55, and dCRP >4 mg/dl (99.3% sensitivity, 100% specificity for all 4 variables); MST >or=10 minutes (100% sensitivity, 99.3% specificity); PMR-AS >or=7 (98.1% sensitivity, 94.3% specificity); VASph >or=2.25 (94.2% sensitivity, 83.6% specificity); and CRP level >or=14.5 mg/liter (66.3% sensitivity, 99.3% specificity).CONCLUSION:Despite inter-individual variations in VASph, PMR-AS was a good indicator of disease activity. However, MST, dMST, dVASph, dPMR-AS, and dCRP performed better than PMR-AS. These variables may be useful in tailoring the glucocorticoid dose to the individual needs of each patient.

1Rheumatology Unit and 2Laboratory of immunology, Brest Teaching Hospital, Brest, France; 3Rheumatology Unit, PitiéSalpétrière Teaching Hospital, Paris, France. Aymeric Binard, MD; Valérie DevauchellePensec, MD, PhD; Bruno Fautrel, MD, PhD; Sandrine Jousse, MD; Pierre Youinou, MD, DSc; Alain Saraux, MD, PhD. Please address correspondence and reprint requests to: Prof. A. Saraux, Rheumatology Unit, Hôpital de la Cavale Blanche, BP 824, F 29609 Brest cedex, France. E-mail: Alain.Saraux@chu-brest.fr Received on December 30, 2006; accepted in revised form on January 19, 2007. © Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2007.

based on the insertion of CD40 ligand (CD40L) on the former cells, into CD40 on the latter. Actually, BAFF can be substituted for CD40L in this process.7 This can favour proliferation of the cells, as suggested by target organ infiltration in BAFF knocked-in (KI) mice with the help of T-cells through TNF. However, mating these mice with TNF knocked-out partner does not protect their offspring from autoimmune infiltration indicating that B-cells have the capacity to proliferate on their own.8 Further insights9 into BAFF have been gained using the hen-egg lysozyme (HEL) model where anti-HEL antibodies (Ab) overcome the anergy on a BAFF-KI background.9 This results from the interplay between the maturation stage, the affinity of the B-cell receptor for HEL and the number of B-lymphocytes competing for BAFF. Obviously, only those autoreactive B-cells that mature sufficiently to acquire responsiveness to survival signals are rescued from apoptosis by BAFF. In this respect, a critical checkpoint, around the T1-T2 sequence of B-cell ontogenesis,10 have been recognized. Owing to the fact that MZ B-cells are most exposed to polyclonal activation, the need to prevent autoreactive BT1-BT2 cells from colonizing this site is paramount. The seminal finding of an autoimmune phenotype in BAFF-KI mice2 has prompted the experts in the field to determine its role in human SLE. A proportion of patients do indeed exhibit elevated levels of soluble BAFF11. The trouble is that the remainder display circulating BAFF levels within or perplexingly, below the normal range. In addition, the parallel with autoAb titres is variable and the correlation with disease activity extremely modest.12 One explanation is that BAFF is not accessible, being inserted into B-cell receptors for BAFF, confined in anti-BAFF Ab-containing immune complexes or excreted in the urines of patients with glomerulonephritis.13 Another explanation is that BAFF is not recognized in the assay, due to the presence of heterotrimers of BAFF and APRIL14 or to the production of aberrant forms of the molecule, such as delta-BAFF or psi-BAFF.15 As BAFF likely contributes to the pathogenesis of SLE, the rationale is building for an approach targeting this system. A human monoclonal Ab has first been generated16. Disappointingly, the protein products of cells transfected with the BR3, TACI or BCMA gene,