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Objective: To obtain results of the second year extension of an original 3 month randomised, placebo controlled trial (and the 1 year extension study) assessing the use of infliximab, a monoclonal antibody to tumour necrosis factor α, for the treatment of patients with ankylosing spondylitis (AS). Methods: Of the 54 patients with AS who completed the first year of the study, 52 continued to receive infliximab 5 mg/kg every 6 weeks up to week 102. The primary end point was the proportion of patients achieving at least 50% improvement from baseline in the Bath AS Disease Activity Index (BASDAI) at week 102. Other assessments included patient and physician global assessments, quality of life as assessed by Short Form-36, Bath AS Functional Index, Bath AS Metrology Index, and C reactive protein (CRP). Results: Improvement in signs and symptoms of AS seen during the first year of the study was sustained during the second year. Forty nine patients (71% of 69 enrolled patients and 49/52 (94%) patients who started year 2) completed the study up to week 102. Thirty (58%) patients achieved at least 50% improvement from baseline in the BASDAI score at week 102. Scores for other efficacy assessments were similar at weeks 54 and 102. Median CRP levels remained low at weeks 54 and 102 (3.9 and 4.3 mg/l, respectively). Side effects during the second year of the study were similar to those of the first year of treatment with infliximab. Conclusions: Patients with AS treated for 2 years with infliximab 5 mg/kg exhibited a good and durable clinical response.

In the past years, the substantially increased number of potent drugs for the therapy of rheumatoid arthritis has made the goal of an early, highly effective therapy more feasible. In addition, combination therapy trials including biologics revealed that joint protection and downregulation of inflammation can be achieved also in stages of active articular destruction, and the detection of novel markers such as antibodies against cyclic citrullinated peptides supports an earlier diagnosis of the disease. The price for these advances, however, are more complex, demanding and expensive therapeutic regimens that need to be handled carefully by the rheumatologist, especially with regard to a new field of side effects inherent with the use of TNF inhibiting agents. Finally, the current therapeutic standard includes also the ongoing clinical and scientific exchange with the orthopedic surgeon to optimize the long-term treatment for the individual patient.

Mit der Grundung des Kompetenznetzes Rheuma, das seit 1999 vom Bundesministerium fur Bildung und Forschung (BMBF) gefordert wird, ist es gelungen, eine fur Deutschland einzigartige Forschungsstruktur zu schaffen: Mediziner und Wissenschaftler von 6 universitaren Rheumazentren (Berlin, Dusseldorf, Erlangen, Freiburg, Hannover und Lubeck/Bad Bramstedt) arbeiten mit Grundlagenforschern des Deutschen Rheumaforschungszentrums, mit rheumatologischen Krankenhausern, Reha-Kliniken und niedergelassenen Rheumatologen zusammen, um gemeinsam nach den Ursachen entzundlich-rheumatischer Systemerkrankungen und nach verbesserten Therapien zu suchen—bundesweit und uber die Grenzen der Disziplinen hinweg. Hauptziel dieser Kooperationen ist es, neue wissenschaftliche Erkenntnisse noch schneller als bisher in verbesserte Diagnose- und Behandlungsverfahren fur Patienten umzusetzen.

As in previous years, the consensus group to consider the use of biological agents was constituted by rheumatologists from the Universities of Erlangen, Leiden, and Vienna in Europe in cooperation with universities in the United States, Canada, and Europe. Pharmaceutical industry support was obtained from a number of companies, but these institutions had no part in the decisions about the specific programme or about the academic participants at this conference. The 158 rheumatologists and bioscientists from 21 countries who attended the consensus conference were chosen from a worldwide group of doctors and other scientists interested in the use of biological agents for the treatment of immune mediated inflammatory diseases. The perspective of this consensus is from the treating doctor’s point of view, rather than from the perspective of those paying for their use. The number of attendees and participants was limited so that not everyone who might have been appropriate could be invited. Additional information has come to light in the past year, both corroborating the major positive effect these drugs have had in rheumatoid arthritis (RA) and other immune mediated inflammatory diseases, as well as documenting possible new and unexpected adverse events. Therefore an update of the previous consensus statement seems both appropriate and necessary ( Ann Rheum Dis2002;61(suppl II):ii2–7 [OpenUrl][1][FREE Full Text][2] ). The consensus statement is annotated to document the credibility of the data supporting it as much as possible. This annotation is that of Shekelle et al and is described in appendix 3.99 All participants reviewed relevant clinical published articles relating to tumour necrosis factor (TNF) and interleukin 1 (IL1) blocking agents. They were given a draft consensus statement and were asked to revise the document in small discussion groups; open discussion of the revisions led to a final document, representing this updated consensus statement. Individual patients differ in the aggressiveness of … [1]: {openurl}?query=rft.jtitle%253DAnnals%2Bof%2Bthe%2BRheumatic%2BDiseases%26rft.stitle%253DAnn%2BRheum%2BDis%26rft.issn%253D0003-4967%26rft.aulast%253DFurst%26rft.auinit1%253DD%2BE%26rft.volume%253D61%26rft.issue%253D90002%26rft.spage%253Dii2%26rft.epage%253D7%26rft.atitle%253DUpdated%2Bconsensus%2Bstatement%2Bon%2Bbiological%2Bagents%2Bfor%2Bthe%2Btreatment%2Bof%2Brheumatoid%2Barthritis%2Band%2Bother%2Brheumatic%2Bdiseases%2B%2528May%2B2002%2529%26rft_id%253Dinfo%253Apmid%252F12379612%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=annrheumdis&resid=61/suppl_2/ii2&atom=%2Fannrheumdis%2F62%2Fsuppl_2%2Fii2.atom

Uber die Epidemiologie der Lyme-Borreliose in Deutschland ist relativ wenig bekannt. Mangels flachendeckender Erhebungen sind kaum Aussagen daruber moglich, ob Erkrankungsfalle generell oder verschiedene Manifestationen wie z. B. die Lyme-Arthritis regional gehauft auftreten. Auserdem existiert bezuglich der Lyme-Borreliose kein standardisiertes diagnostisches und therapeutisches Vorgehen. Aus diesen Grunden wurde eine bundesweite Fragebogenaktion in der Arzteschaft durchgefuhrt. Es sollten epidemiologische Daten und Erkenntnisse uber die Diagnostik- und Therapiegewohnheiten von praktischen Arzten und verschiedenen Facharzten gewonnen werden. Weiterhin sollte gepruft werden, mit welchem Erfolg die verschiedenen Antibiotika eingesetzt wurden. Der entworfene Fragebogen erschien als Beilage in zwei Ausgaben des Deutschen Arzteblattes und wurde teilweise uber den Ausendienst einer pharmazeutischen Firma verteilt. Der Erhebungszeitraum erstreckte sich vom 1. Marz 1998 bis zum 28. Februar 1999. Mit der Meldung der Patienten sollten Angaben zum Infektionsort, zur Diagnose, zur klinischen Symptomatik, zum diagnostischen Vorgehen, zur Therapie und zum Behandlungserfolg gemacht werden. Zur Beantwortung von Fragen zur Diagnostik und Therapie der Lyme-Borreliose wurde an der Charite ein sog. “Lyme-Telefon“ eingerichtet. Es wurden insgesamt 3935 Patienten gemeldet. Das Durchschnittsalter betrug 43,3 Jahre mit Erkrankungsgipfeln um das 10. sowie das 60. Lebensjahr. 30,4% der Erhebungsbogen wurden von Allgemeinmedizinern eingesandt, 17,6% von Dermatologen, 15,7% von Padiatern, 9,7% von Internisten, 6,9% von praktischen Arzten und 2,7% von Neurologen. 83% aller gemeldeten Patienten hatten kein besonderes Infektionsrisiko. Haufigste Manifestation zum Zeitpunkt der Arztkonsultation war das Erythema migrans (EM), das bei 50,9% aller Patienten vorkam, 21,3% litten an Allgemeinsymptomen. Interessanterweise litten 24,5% an Arthritiden (14,7% Mon- oder Oligoarthritis; 9,8% Polyarthritis), die damit sogar haufiger waren als neurologische Manifestationen (18,4%). Nur 16% der Patienten, die sich mit einer akuten Neuroborreliose vorstellten, und 32% der Arthritis-Patienten erinnerten ein EM. Es wurden 189 Patienten (4,8%) mit einer Lymphadenosis cutis benigna und 100 Patienten (2,5%) mit einer Acrodermatitis chronica atrophicans gemeldet. Bei 80,4% der Patienten wurde eine positive Borrelien-Serologie angegeben. In einigen wenigen Fallen wurde die Diagnose mittels Erregerisolierung, PCR oder Histologie gesichert. 3754 Patienten wurden antibiotisch behandelt; dabei wurden bis zu 6 verschiedene Substanzen verabreicht. Das als Initial- und Folgetherapie am haufigsten eingesetzte Antibiotikum war Doxycyclin (50,4%), gefolgt von Ceftriaxon (22,4%), Amoxicillin (13,6%), Penicillin (7%) und Erythromycin (4,2%); die Verschreibungen unterschieden sich hinsichtlich klinischer Manifestation und Facharztgruppe. Nicht evaluierte Therapieverfahren wurden bei weniger als 10% der gemeldeten Patienten durchgefuhrt. Die Lyme-Borreliose ist in ganz Deutschland endemisch. Das EM ist die haufigste Manifestation, gefolgt von Lyme-Arthritis und Neuroborreliose. Maximal ein Drittel aller Patienten mit einer disseminierten oder chronischen Lyme-Borreliose erinnert sich an ein EM. Die Mehrzahl der sich an der Studie beteiligenden Arzte halt sich an evaluierte Therapieverfahren.

Autoimmunkrankheiten und Allergien sind durch eine Storung der immunologischen Toleranz gegen Selbstantigene gekennzeichnet. Durch neue molekularbiologische Untersuchungstechniken ist das Wissen uber die Mechanismen der immunologischen Toleranz in den letzten Jahren enorm gestiegen. Die Herausforderung der Zukunft besteht darin, diese Erkenntnisse in therapeutische Strategien umzusetzen. Der vorliegende Beitrag prasentiert eine Ubersicht zur dominanten Rolle der T-Lymphozyten bei Immuntoleranz und Autoimmunitat, beschreibt die bisherigen experimentellen und ersten klinischen Ergebnisse immunmodulatorischer Therapieansatze und gibt einen Ausblick auf mogliche zukunftige Entwicklungen.

Contains fulltext : 142630.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To evaluate efficacy, dose response, safety, and tolerability of adalimumab (D2E7) in disease modifying antirheumatic drug (DMARD) refractory patients with longstanding, active rheumatoid arthritis (RA). METHODS: During a 12 week, double blind, placebo controlled study, 284 patients were randomly allocated to receive weekly subcutaneous injections of adalimumab 20 mg (n = 72), 40 mg (n = 70), or 80 mg (n = 72) or placebo (n = 70) without concomitant DMARDs. RESULTS: Adalimumab significantly improved the signs and symptoms of RA for all efficacy measures. ACR20 responses with adalimumab were significant at each assessment versus placebo (p

A s in previous years, the consensus group to consider the use of biological agents was formed by an organising committee constituted of rheumatologists from the Universities of Erlangen, Leiden, and Vienna in Europe in cooperation with universities in the United States, Canada, and Europe. Pharmaceutical industry support was obtained from a number of companies, but these institutions had no part in the decisions about the specific programme or about the academic participants at this conference. The 158 rheumatologists and bioscientists from 22 countries who attended the consensus conference were chosen from a worldwide group of people felt to have experience or interest in the use of biological agents for the treatment of rheumatoid arthritis (RA) and other rheumatic diseases. Unfortunately, the number of attendees and participants was limited so that not everyone who might have been appropriate could be invited. Additional information has come to light in the past year, both corroborating the major positive effect these drugs have had in RA and documenting possible new and unexpected adverse events. In addition, the first of a new class of targeted biological agents, interleukin 1 (IL1) blocking agents, has become available. Therefore an update of the previous consensus statement1 seems both appropriate and necessary. In the present update the consensus statement is annotated to document the credibility of the data supporting it as much as possible. This annotation is that of Shekelle et al and is described in appendix 3.2 All participants reviewed relevant clinical published articles relating to tumour necrosis factor (TNF) and IL1 blocking agents. They were given a draft consensus statement and were asked to revise the document in small discussion groups; open discussion of the revisions led to a final document, representing this updated consensus statement. Individual patients differ in the aggressiveness of their …

Die rheumatoide Arthritis ist eine fortschreitende und systemische Erkrankung unbekannter Atiologie, die zu Gelenkzerstorung fuhrt und nicht selten mit extraartikularen Manifestationen verbunden ist. Eine Heilung der rheumatoiden Arthritis ist gegenwartig nicht moglich. Verglichen mit herkommlichen antirheumatischen krankheitsbeeinflussenden Medikamenten (DMARDs) zeigen Biologika wie Tumornekrosefaktor (TNF)-α- und Interleukin (IL)-1-Blocker insbesondere bei therapierefraktaren Verlaufen eine bessere Wirksamkeit und Sicherheit. Im Folgenden werden die neuen Wirkstoffe Infliximab, Etanercept und Anakinra sowie weitere Zytokinhemmer vorgestellt. Um ihre Anwendung und mogliche noch unbekannte Langzeiteffekte zu kontrollieren, wurde ein Netz aus internationalen und nationalen Gremien ins Leben gerufen. Die aktuellen Empfehlungen zur Behandlung der rheumatoiden Arthritis mit Biologika werden vorgestellt, und die Kosten-Nutzen-Relation wird diskutiert.

The recurrence of widespread and diverse vascular lesions is a hallmark of systemic lupus erythematosus (SLE). Inflammatory and thrombotic mechanisms almost invariably associated with circulating antiphospholipidantibodies play a role in the pathogenesisof SLE-related vascular disease. Both mechanisms can coexist in the same patient. Vasculitis is most commonly induced by the local deposition of immune complexes. However, some SLE patients have an inflammatory complement-mediated vascular injury in the absence of immune complex deposition.We report on a fatal case of disseminated intravascular coagulation (DIC) in a young woman with active SLE. Hemorrhagic lesions due to localized intravascular coagulation (Shwartzman phenomenon) preceded disseminated intravascular coagulation accompanied by disseminated cardiac necrosis. Immune complex ‘independent’ and other mechanisms of vascular injury and states of hypercoagulability will be discussed.

Rheumatoid factor and antinuclear antibodies are detectable in many different conditions and are ordered by various specialities. The interpretation of results, however, is quite complex.The objective of this article is to help apply these tests correctly and enable an accurate interpretation of the test results. Furthermore, we describe the steps in the differential diagnostics for selecting those patients who need to be referred to a rheumatologist.

The working profile of university hospitals includes medical education, research and implementation of medical innovations as well as large volume patient care. University hospitals offer inpatient, day care and outpatient care which are of essential value for many patients. Besides their primary role in treating rare and orphan diseases and complex cases, they increasingly support general patient care. There are different kinds of outpatient access and treatment options available. The funding of university hospitals and clinics is based on general university funding, income from third party funds for research, income from patient care and funding from the federal states for investments. In recent years these institutions have suffered more and more from economic deficits, a lack of investment and inadequate funding whereby high performance medicine cannot be sufficiently supported. Professors are developing into scientific managers and are frequently assessed by economic outcome and competitiveness. At the same time they are embedded in the structures of the university and are not in the position to make decisions on their own, in contrast to doctors in private practices. Therefore, processes, necessary investments and restructuring are significantly delayed. There is a need to develop strategies for long-term funding and providing university hospitals and clinics with the means to deliver the necessary services.

Rheumatoid Arthritis is a progressive and systemic inflammatory disorder of unknown etiology that frequently leads to joint destruction accompanied by multi-system extra-articular manifestations. No curative therapy is available today. Compared to usual Disease Modifying Antirheumatic Drugs (DMARDs), biologicals such as tumor necrosis factor (TNF) α- and interleukin (IL) 1-inhibitors appear to offer greater efficacy and safety, especially in refractory cases. This article deals with the new agents infliximab, etanercept, and anakinra as well as with additional newly developed cytokine-inhibitors. In order to control their use and possible unknown long-term effects, a network of international and national committees has been installed. The actual recommendations for the treatment of rheumatoid arthritis with biologicals are presented, and the cost-benefit relation is discussed.

Treatment with rituximab (RTX) has been approved since 2006 for patients with rheumatoid arthritis who previously failed to respond to tumor necrosis factor (TNF) inhibitor therapy or who experienced side effects. In these updated treatment recommendations new data relating to evaluation of the therapeutic response, retreatment, the role of predictive factors as well as safety data are incorporated and discussed.

Objective To study the relationship of spinal inflammation and fatty degeneration (FD) as detected by MRI and new bone formation seen on conventional radiographs (CRs) in ankylosing spondylitis (AS). Methods CRs at baseline, 2 years and 5 years and spinal MRIs at baseline and 2 years of 73 AS patients treated with infliximab in European AS Infliximab Cohort were available. Relative risks (RR) were calculated with a general linear model after adjustment for within-patient variation. Results In a total of 1466 vertebral edges (VEs) without baseline syndesmophytes, 61 syndesmophytes developed at 5 years, the majority of which (57.4%) had no corresponding detectable MRI lesions at baseline. VEs with both inflammation and FD at baseline had the highest risk (RR 3.3, p=0.009) for syndesmophyte formation at 5 years, followed by VEs that developed new FD or did not resolve FD at 2 years (RR=2.3, p=0.034), while inflammation at baseline with no FD at 2 years had the lowest risk for syndesmophyte formation at 5 years (RR=0.8). Of the VEs with inflammation at baseline, >70% resolved completely, 28.8% turned into FD after 2 years, but only 1 syndesmophyte developed within 5 years. Conclusions Parallel occurrence of inflammation and FD at baseline and development of FD without prior inflammation after 2 years were significantly associated with syndesmophyte formation after 5 years of anti-tumour necrosis factor (TNF) therapy. However, the sequence ‘inflammation–FD–new bone formation’ was rarely observed, an argument against the TNF-brake hypothesis. Whether an early suppression of inflammation leads to a decrease of the risk for new bone formation remains to be demonstrated.

OBJECTIVES Recent evidence suggests that prolactin (PRL) plays a part in the pathogenesis of systemic lupus erythematosus (SLE). Because B cell hyperreactivity and autoantibodies are characteristic hallmarks of SLE, this study aimed at assessing the impact of this pituitary hormone on IgG production by stimulating peripheral blood mononuclear cells (PBMC) with PRL. METHODS PBMC from 11 patients with SLE assessed by the ECLAM score and eight healthy controls were incubated with PRL and cultured for seven days. IgG production was measured by enzyme linked immunosorbent assay (ELISA). RESULTS Spontaneous IgG production of SLE PBMC was significantly enhanced compared with that found in healthy controls. After PRL stimulation, the IgG concentrations of supernatants from SLE PBMC were significantly higher than those of unstimulated PBMC (median 394 ng/ml). Of note, the physiological concentration of PRL (20 ng/ml) induced IgG production more effectively (median 1139 ng/ml) than PRL at 100 ng/ml (median 1029 ng/ml). In contrast, preincubation with PRL did not stimulate IgG production in normal PBMC. A significant correlation between PRL induced IgG production and the disease activity (ECLAM) of the patients with SLE was seen. Moreover, the maximum amount of PRL induced IgG depended on the serum PRL concentrations of the patients with SLE. CONCLUSIONS The results suggest that PBMC from patients with SLE have an extraordinarily high susceptibility to PRL, showing the most striking effect at a concentration usually found in vivo. This indicates a potential role for mild hyperprolactinaemia in the pathogenesis of SLE, influencing both IgG production and disease activity.

Die Therapie entzundlich-rheumatischer Erkrankungen hat in den letzten Jahren deutliche Fortschritte gemacht. So konnte die Progression der rheumatoiden Arthritis in vielen Fallen verlangsamt werden, die Lebenserwartung bei den primar systemischen Vaskulitiden oder beim systemischen Lupus erythematodes konnte deutlich gesteigert werden. Der vorliegende Beitrag stellt nicht nur die gegenwartige Standardtherapie verschiedener entzundlich rheumatischer Erkrankungen dar, sondern gibt auch einen Uberblick uber neueste Therapiestrategien, die in Zukunft das therapeutische Spektrum deutlich erweitern werden. So kann beispielsweise der Einsatz von TNF-α-blockierenden Substanzen die Therapie dieser Erkrankungen effektiv bereichern. Die Zielrichtung weiterer Forschung ist damit gestellt.

Im Namen aller Beteiligten mochten wir Ihnen das Kompetenznetz Rheuma vorstellen. Dieser Artikel soll Ihnen einen ersten Einblick in die Aufgaben, Strukturen und Ziele unseres Projektes geben. Das Kompetenznetz Rheuma geht auf eine Initiative des Bundesministeriums fur Bildung und Forschung zuruck. Unter mehr als 150 Antragstellern hat das Ministerium im Rahmen eines Wettbewerbs neun Kompetenznetzwerke in der Medizin fur eine spezielle Forderung ausgewahlt. Das Ziel war, die in Deutschland vorhandene, aber bundesweit zersplitterte Kompetenz zu gesundheitspolitisch bedeutenden Krankheitsbildern zu bundeln und dadurch effizienter zu gestalten. Das Kompetenznetz Rheuma ist einer der Gewinner und wird uber einen Zeitraum von bis zu funf Jahren mit bis zu 5Mio. Mark jahrlich unterstutzt. Im Kompetenznetz Rheuma schliesen sich die verschiedenen Ebenen der Rheumatologie zusammen: die Grundlagenforschung, die Versorgungsforschung, die Universitatskliniken, die rheumatologischen Krankenhauser und Rehabilitationskliniken, die niedergelassenen Rheumatologen und die Hausarzte. Der Wissens- und Informationstransfer untereinander wird durch horizontale und vertikale Vernetzung sichergestellt. Ein wesentliches Ziel besteht darin, die Wege von der Laborbank bis zum Krankenbett zu verkurzen. Denn der enge Verbund von Grundlagenforschung, Krankenbetreuung und Dokumentation bietet einzigartige Moglichkeiten, neue Forschungsergebnisse zugig in die Patientenversorgung zu integrieren und bestehende Defizite zu erkennen und auszuschalten. Getragen und weiterentwickelt wird das Kompetenznetz Rheuma von den sechs antragstellenden rheumatologischen Kompetenzzentren in Berlin, Dusseldorf, Erlangen, Freiburg, Hannover und Lubeck/ Bad Bramstedt. Das Netzwerk soll aber kein in sich geschlossenes Projekt bleiben. Alle Interessierten sind herzlich eingeladen, sich daran zu beteiligen. Wir freuen uns also uber Ihre Vorschlage, Diskussionsbeitrage und Anfragen! Gezielte Informationen zu den Teilprojekten konnen Sie bei den in dieser Artikel genannten Ansprechpartnern gern anfordern.

A 42-yr-old woman with dermatomyositis had two myocardial infarctions, episodes of acute chest pain and an acute lung oedema. These events were initially misinterpreted as atherosclerotic ischaemic heart disease accompanying the autoimmune disease. The lack of improvement of cardiac symptoms with anti-ischaemic and immunosuppressive drugs indicated other mechanisms. Intracoronary drug provocation as well as myocardial biopsy revealed a coincidence of small-vessel disease and vasospastic angina as a cause for the severe cardiac symptoms. After initiating therapy with high doses of calcium channel blockers, marked improvement of cardiac symptoms occurred. In the pathogenesis of cardiac involvement in dermatomyositis, two different mechanisms should be considered: inflammatory processes due to dermatomyositis and vasoconstriction caused by an impaired regulation of vascular tone, such as abnormal vessel reactivity or disturbed neuropeptide release. Signs of this generalized vasopathy are Raynaud's phenomenon, Prinzmetal's angina and small-vessel disease, which can coincide. In patients with severe cardiac symptoms and autoimmune diseases, Prinzmetal's angina should be excluded by intracoronary drug provocation using acetylcholine.

Drugs used for managing rheumatoid arthritis (RA) are designated disease-modifying antirheumatic drugs (DMARDs) if they reduce inflammation and pain, limit joint destruction, and improve long-term disease outcome. Glucocorticoids have long been known to have anti-inflammatory, immunosuppressive, and pain-reducing effects. Moreover, they have been shown in recent clinical trials, and also very recently in a systemic analysis of the results of these studies, to contribute to inhibition of the radiographic progression of RA. For these reasons, glucocorticoids can be considered DMARDs if they are used to treat patients suffering from early RA and, according to the current knowledge, are used in combination with other DMARDs.

OBJECTIVE—The autoantigen p68 is a target of autoantibodies as well as autoreactive T cells with a high specificity in rheumatoid arthritis (RA). The binding characteristics of the autoantibodies to their antigen were now analysed biochemically and cytologically. METHODS—Deglycosylation techniques as well as lectin and sugar competition experiments were performed to p68 to discover if the antibodies detected a glycoepitope. Its antigenicity was investigated applying anti-p68 antibodies derived from RA patients in comparison with polyclonal rabbit anti-p68 antibodies. RESULTS—p68 specific antibodies from RA patients did not to bind to p68 that had been deglycosylated by alkaline β-elimination, O-glycosidase or periodate treatment. In contrast, binding of p68 specific antibodies raised in rabbit was unaffected by either deglycosylation protocol. Furthermore, lectins specific for the carbohydrate N-acetylglucosamine competed with p68 specific antibodies from RA patients for antigen binding. N-acetylglucosamine by itself also competed with patient derived anti-p68 antibodies for p68 binding. Again, rabbit anti-p68 antibodies did not elicit these competitive effects. Applying cytoimmunofluorescence, p68 was present in the cytoplasm or endoplasmic reticulum and also in low abundance on the cell surface. Under heatshock conditions, p68 was detectable in the nucleus. CONCLUSIONS—Autoimmunity to p68 during RA is carried by anti-carbohydrate autoantibodies. The carbohydrate modification of p68 appears to be N-acetylglucosamine, which may reflect the regulation of intracellular localisation of the antigen. It is hypothesised that a shift in glycosylation pattern accompanied by an unphysiological localisation of the antigen could trigger antigenicity of p68 during the pathogenesis of RA. Keywords: carbohydrate epitope; autoantibodies; autoantigen; rheumatoid arthritis

We present the rare case of a 60 year old man with Mycobacterium kansasii infection who complained of severe joint pain and swelling, predominantly of the right shoulder. Non-steroidal anti-inflammatory drugs (NSAIDs) led to pain relief. The swelling around the right shoulder was unsuccessfully treated by aspiration followed by surgery. As a steam engine driver the patient was exposed to asbestos and inorganic dusts (coal, mineral/silicate). The rheumatological examination disclosed a mobile, firm, elastic swelling over the dorsal aspect of the left elbow, tenderness and mild swelling of both wrists, the metacarpophalangeal (MCP) joints, the third fingers of both hands, and the MCP joints of both thumbs. Joint effusion was palpated around the right shoulder and mobility was limited owing to pain. Inflammatory measures were raised and angiotensin converting enzyme was within normal range. No evidence of acid fast rods …

The objectives of this study are to evaluate a new semi-quantitative (0-5) musculoskeletal ultrasound (US) erosion score in patients with rheumatoid arthritis (RA) and to prove its usefulness in the detection of disease activity and success of therapy. Thirty-eight patients with RA (mean disease duration 10.1 ± 11.9 years) were enrolled. Start or change of therapy (DMARD/biologics) was an inclusion criterion. DAS28, laboratory (ESR and CRP) and US data were evaluated before new therapy initiation and after 1, 3, 6 and 12 months. Thirteen joints of the clinically more affected hand and forefoot (wrist and MCP, PIP, MTP joints 2-5) were analyzed for synovitis in grayscale (GS) and power Doppler (PD) US, tenosynovitis/paratenonitis in GS/PDUS (wrist, MCP level) and for erosions. Erosions were analyzed by a new semi-quantitative score (grade 0, no erosion; grade 1,1 mm, grade 2, 1 to2 mm; grade 3, 2 to ≤3 mm; grade 4,3 mm; grade 5, multiple bone erosions). After 12 months, DAS28 decreased from 4.5 to 3.4 (p 0.001), the synovitis score in GSUS from 26.3 to 12.8 (p = 0.001) and the synovitis score in PDUS from 10.6 to 4.1 (p 0.001). The erosion score decreased from 21.5 to 18.1 (p = 0.046). There were longitudinal significant correlations between the new erosion score and both the DAS28 (r = 0.368; p = 0.025) and the synovitis score in PDUS (r = 0.365; p = 0.026) over a 1-year follow-up period. The new erosion score might be a useful tool for the evaluation of erosive changes by US in RA patients. In the course of DMARD and biologic therapy, it was responsive under 1-year follow-up examination.

In contrast to the restrictive nature of randomised controlled trials (RCT), non-interventional studies (NIS) investigate the features of a therapy in daily clinical practice. The observational plan of NIS does not dictate a treatment strategy, but is based on the product label. Unlike RCT, NIS therefore have no actual inclusion and exclusion criteria, allowing the study of broad heterogeneous patient populations.NIS carried out in Germany with support from the pharmaceutical industry and investigating the use of biologics for the treatment of rheumatoid arthritis were identified and their findings were compared with those from the RCT of the respective biologic.Analysis of the identified NIS revealed the following: (1) populations in NIS were on average more than twice as large as in RCT, (2) patient characteristics in NIS and RCT were different, (3) the effectiveness of biologics in NIS was comparable to the efficacy observed in RCT, and (4) NIS collected supplementary data, e.g. on usage and dosing in clinical practice.NIS represent an important tool for the assessment of daily clinical practice. Despite methodological drawbacks, NIS provide valuable data that contribute to a more complete picture of the value of treatment with biologics. The English version of this article is available at SpringerLink (under "Supplemental").

Idiopathic inflammatory myopathies (IIM) are chronic inflammatory diseases of muscle characterized by proximal muscle weakness. There are three main groups of diseases, dermatomyositis, polymyositis and inclusion body myositis. The muscle tissue is invaded by the humoral autoantibody producing immune system (B-cells) and by the cellular immune system with autoaggressive and inflammation modulating cells (e.g. dendritic cells, monocytes/macrophages, CD4 + and CD8 + T-cells and natural killer cells). The presence of specific or associated autoantibodies and inflammatory cellular infiltrates with cytotoxic and immune autoreactive properties are characteristic for IIM diseases. The pathogenesis is still unknown; nevertheless, there are several hints that exogenic factors might be involved in initiation and disease progression and bacterial, fungal and viral infections are thought to be possible initiators. Up to now information on prognostic markers to help with decision-making for individual treatment are limited. In addition, there has been only limited therapeutic success including conventional or novel drugs and biologicals and comparative validation studies are needed using similar outcome measurements. Moreover, to facilitate the use and development of novel therapies, elaboration of intracellular and cell-specific regulation could be useful to understand the etiopathogenesis and allow a better diagnosis, prognosis and possibly also a prediction for individualized subgroup treatment.

Objective. The main objective of this study was to evaluate the 7-joint ultrasound (US7) score by detailed joint region analysis of an arthritis patient cohort.Methods. The US7 score examines the clinically most affected wrist, MCP and PIP II, III, MTP II, and V joints for synovitis, tenosynovitis/paratenonitis, and erosions. Forty-five patients with rheumatoid arthritis (RA) (84.4%) and spondyloarthritis with polyarticular peripheral arthritis (PsA 13.3%; AS 2.2%) with a median disease duration of 6.5 yrs (range 7.5 mths–47.6 yrs) were included and examined at baseline and 3, 6, and 12 months after starting or changing therapy (DMARD/biologic). In this study, detailed US7 score joint region analysis was firstly performed.Results. The joint region analysis performed at baseline disclosed synovitis in 95.6% of affected wrists in the dorsal aspect by greyscale (GS) US where Grade 2 (moderate) was most often (48.9%) detected. Palmar wrist regions presented Grade 1 (minor) capsule elevation in 40% and Grade 2 (moderate synovitis) in 37.8%. Tenosynovitis of the extensor carpi ulnaris (ECU) tendon was found in 40%, with PD activity in 6.6%. Most of the erosions in MCP II were detected in the radial (68.9%), followed by the dorsal (48.9%) and palmar (44.4%) aspects. In MTP V, erosions were seen in 75.6% from lateral.Conclusions. Synovitis in GSUS was more often detected in the wrist in the dorsal than in the palmar aspect. ECU tendon involvement was frequent. Most erosions were found in the lateral scan of MTP V and the medial (radial) scan of MCP II.

Synovial fluid (SF) was found to possess stimulatory capacity for the proliferation of T cell clones derived from patients with rheumatoid arthritis (RA) when cultured together with IL-2. Using chromatography technique and gel electrophoresis, a synovial fluid protein with an apparent m.w. of 205 kDa (p205) was isolated that demonstrated a bioactivity analogous to that obtained with native synovial fluid. After electroelution, p205 dissociated into 70-kDa fragment(s). Upon IEF, it appeared as a single band with an isoelectric point of 6.5, suggesting a noncovalently bound trimer complex. Amino acid sequences of the whole protein and of tryptic peptides were determined by N terminal sequencing. The N terminal amino acid sequence of the 70-kDa fragment and of the tryptic peptides showed no identity to recently described protein sequences. One peptide matched, in 11 amino acid residues, with the human IgG1-4 constant heavy chain and rheumatoid factor (RF) binding region. The p205 induced the proliferation of peripheral blood T cells and long term T cell cultures that had been raised by alternate stimulation with IL-2 and p205. In a similar approach, synovial lining cells were shown to release a protein with biochemical characteristics similar to the synovial fluid-derived p205. Western blot analysis revealed the binding of RF-containing sera to p205, which was diminished by absorption with an RF reagent. These observations suggest that p205 is expressed by synovial cells and may be a target for T and B cells in RA.

Background RA leads to high burden on patient (pt) work, functioning and quality of life. Certolizumab pegol (CZP)+MTX improves physical function,1 and workplace and household productivity,2,3 in established and early active RA. Here we report impact of maintaining, reducing frequency or stopping CZP from Week (Wk) 52 to 104 in pts who achieved sustained low disease activity (sLDA) following 1 year (yr) of CZP+optimized MTX. Objectives To assess effect of 2 dosing frequencies of CZP+MTX vs stopping CZP on physical function and workplace/household productivity in Period 2 of C-EARLY, a phase 3 study in early RA pts with severe progressive disease. Methods CZP+MTX-treated pts achieving sLDA (DAS28[ESR]≤3.2 at Wks40 and 52) in C-EARLY Period 1 (NCT01519791)4 entered Period 2 (NCT01521923), a randomized, double-blind study. Pts were randomized 2:3:2 to CZP standard dose (200mg Q2W+MTX), CZP reduced-frequency dose (200mg Q4W+MTX) or CZP stopped (PBO+MTX). Physical function (HAQ-DI) and %pts achieving normative physical function (HAQ-DI≤0.5) from Wk52 to 104 are reported (ANCOVA model with factors treatment, region, time since diagnosis at BL [≤4 vs >4 months], and BL/Wk52 values as covariate and logistic regression models [treatment, region and time since diagnosis at BL as factors] respectively; CZP stopped as comparator; LOCF). Workplace/household productivity (Work Productivity Survey, WPS)5 at Wk52 and 104 are reported (LOCF); non-parametric bootstrap-t method (CZP stopped as comparator). Results In Period 2, 289 pts were included in the full analysis set: CZP Q2W+MTX (n=84), CZP Q4W+MTX (n=126) or PBO+MTX (n=79). Improvements in physical function were maintained from Wk52 to 104 in CZP Q2W+MTX (HAQ-DI mean [SD] 0.32 [0.42] to 0.37 [0.48], respectively) and CZP Q4W+MTX (0.33 [0.49] to 0.41 [0.57]), whereas deterioration was seen in PBO+MTX (0.33 [0.47] to 0.57 [0.65]). %pts with normative function was generally maintained between Wk52 to 104 in CZP Q2W+MTX (80.7% to 71.4%) and CZP Q4W+MTX (80.2% to 70.6%), but decreased in PBO+MTX pts (75.9% to 57.0%). At Wk104, employed CZP Q2W+MTX and CZP Q4W+MTX pts maintained on average the improvements in workplace productivity, whereas worsening was seen in pts stopping CZP (Table). Similar trends were observed in household productivity and need for regular assistance (Table). Conclusions Pts continuing CZP treatment (both dose frequencies) after 1yr further maintained improvements at 2yrs in physical function and workplace/household productivity, compared with pts who stopped CZP. References Strand V. Arthritis Res Ther 2009;11:R170; Kavanaugh A. Arthritis Care Res 2009;61(11);1592–1600; Emery P. Ann Rheum Dis 2015;74(S2);712; Weinblatt M. Arthritis Rheumatol. 2015;67(S10); Osterhaus J. Arthritis Res Ther 2009;11:R73 Acknowledgement The authors acknowledge Costello Medical Consulting, funded by UCB Pharma, for writing and editorial assistance. Disclosure of Interest C. Bingham Consultant for: UCB Pharma, P. Emery Consultant for: Bristol-Myers Squibb, Pfizer, MSD, AbbVie, UCB Pharma, Roche, Schering Plough, Novartis and Samsung, M. Weinblatt Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo Bioscience and UCB Pharma, Consultant for: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Crescendo Bioscience, Lilly, MedImmune, Merck, Novartis, Pfizer, Roche and UCB Pharma, G.-R. Burmester Consultant for: AbbVie, MSD, Pfizer, Roche and UCB Pharma, D. Furst Grant/research support from: Abbott, Actelion, Amgen, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, NIH, Novartis, Pfizer, Roche/Genentech and UCB Pharma, Consultant for: Abbott, Actelion, Amgen, Bristol-Myers Squibb, Biogen IDEC, Janssen, Gilead, GlaxoSmithKline, NIH, Novartis, Pfizer, Roche/Genentech and UCB Pharma, X. Mariette Grant/research support from: Pfizer, GlaxoSmithKline and Roche. Consulting fees from Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche, UCB Pharma and Sanofi-Aventis, R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, Pfizer, Roche, UCB Pharma, Consultant for: AbbVie, Biotest, BMS, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB Pharma, Vertex, B. VanLunen Employee of: UCB Pharma, O. Purcaru Employee of: UCB Pharma, V. Bykerk: None declared

Background Mavrilimumab, a fully human monoclonal antibody, which targets granulocyte-macrophage colony-stimulating factor receptor-α, has demonstrated efficacy and an acceptable safety profile in prior 12- and 24-week studies.1,2 Objectives This analysis evaluated all long-term (LT) safety and efficacy, through 74 weeks of treatment, of mavrilimumab. Methods This open-label extension (OLE) study (NCT01712399) enrolled adult rheumatoid arthritis (RA) patients (pts) who had completed the EARTH EXPLORER 12 and 2 (NCT01715896) Phase IIb studies or were rescued as inadequate responders (from Week 12). Pts received subcutaneous mavrilimumab 100 mg every other week (eow), consistent with data from the Phase IIa study1. The primary objective was to assess the LT risk:benefit ratio of mavrilimumab via evaluation of i) Treatment emergent adverse events (TEAEs), TE serious AEs (TESAEs), and independently adjudicated pulmonary function tests (PFTs) ii) Exploratory LT efficacy endpoints (DAS28–CRP/ACR responses). AEs with onset date after start of mavrilimumab are presented. Change from baseline (BL) in modified Total Sharp Score (mTSS) was used to explore radiographic progression in EARTH EXPLORER 1 pts. Results At the 74 week (includes original study) cutoff, 391 pts had been enrolled in the OLE study. Of these, 329 (84.1%) continued on treatment, 62 (15.9%) discontinued (due to withdrawal of consent, 9 [2.3%]; adverse event, 7 [1.8%]; non study-related site closure, 20 [5.1%]; other, 24 [6.1%]; lost-to-follow-up, 1 [0.3%]; death [sudden cardiac arrest, preferred term cardiopulmonary failure], 1 [0.3%]), and 239 (61.1%) were assessed for efficacy at Week 74. Between the Phase IIb and OLE studies, 440 pts received mavrilimumab, with a safety exposure of 603 pt years (yr) and median duration of 1.6 yr. Most common TEAEs (n [/100 pt yr]) were nasopharyngitis (51 [8.45]), bronchitis (36 [5.97]) and hypertension (32 [5.30]); the serious infection rate was 1.82/100 pt yr. Pulmonary events/defined PFT changes occurred in a few pts and were generally transient with no signal identified (Table). Mavrilimumab demonstrated sustained efficacy (DAS28–CRP/ACR responses) (Table). After 74 weeks of treatment, 68% of pts showed no radiographic progression ( Conclusions Mavrilimumab continues to demonstrate a sustained efficacy and safety profile in pts with active RA, over the 74 week treatment duration reported. Although mavrilimumab 100 mg eow is suboptimal compared with 150 mg eow in DMARD-IR pts,2 efficacy results are comparable with those of previous studies.1,2 References Burmester G, et al. Ann Rheum Dis 2013;72:1445–1452 Burmester G, et al. Arthritis Rheum 2014;66:S1231 Acknowledgement Funded by MedImmune. Editorial assistance: K Alexander, QXV Comms, an Ashfield business, UK Joint senior authors: D. Close and M. Weinblatt Disclosure of Interest G. Burmester Consultant for: MedImmune, I. McInnes Grant/research support from: Research award to University of Glasgow, Consultant for: MedImmune, AstraZeneca, J. Kremer Shareholder of: Corrona, Grant/research support from: Abbvie, Amgen, Genentech, Lilly, Pfizer, Consultant for: Abbvie, Amgen, BMS, Genentech, Lilly, Pfizer, Employee of: Corrona, P. Miranda Grant/research support from: Clinical trials Amgen, Medimmune, Janssen, Pfizer, Celltrion, Abbott, Sanofi, Actelion, Merck & Co, Boehringer, BMS, Consultant for: Pfizer for Etanecept (fee less than USD5000), J. Vencovský Consultant for: Pfizer, Servier, Samsumg, Eli lilley, BMS, Novartis, A. Godwood Shareholder of: AstraZeneca, Employee of: MedImmune, M. Albulescu Employee of: MedImmune, D. Close, Employee of: MedImmune, M. Weinblatt, Grant/research support from: BMS, UCB, Crescendo Bioscience, Consultant for: MedImmune, AstraZeneca, Amgen, Abbvie, BMS, Crescendo Bioscience, Lilly, Pfizer, UCB, Roche

Background Clinical remission is an important treatment goal in rheumatoid arthritis (RA) and is associated with improved physical function and quality of life.1,2 In the phase 3 TARGET study (NCT01709578), sarilumab (150 or 200 mg subcutaneously every 2 weeks + conventional synthetic disease-modifying antirheumatic drugs [csDMARDs]) demonstrated efficacy in adults with active, moderate-to-severe RA and inadequate response to tumor necrosis factor (TNF) inhibitors.3 Infections, neutropenia, injection site reactions, and increased transaminases were among the most common treatment-emergent adverse events.3 Objectives This analysis assessed the proportions of patients achieving clinical remission measured by 4 different disease activity measures in a difficult-to-treat patient population with active RA and inadequate response or intolerance to ≥1 prior TNF inhibitor(s). Methods Four definitions of remission were used: 28-joint disease activity score by C-reactive protein (DAS28-CRP) Results Baseline demographic and disease characteristics were balanced among the 3 treatment groups. At week (wk) 12 and wk 24, the proportion of patients achieving DAS28-CRP Conclusions Sarilumab induced remission (using a broad range of definitions) as early as 12 weeks after initiation of therapy in patients with an inadequate response to TNF inhibitors. Patients with remission generally had improvements in physical function and fatigue as well. References Smolen et al. Ann Rheum Dis. 2014;73:492–509. Radner et al. Arthritis Res Ther. 2014;16:R56. Fleischmann et al. Presented at: ACR; November 7–11, 2015; San Francisco, CA. Acknowledgement This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Editorial assistance was provided by Kristi Porter, PhD, MedThink SciCom, and funded by Sanofi and Regeneron Pharmaceuticals, Inc. Disclosure of Interest G. Burmester Grant/research support from: AbbVie, Pfizer, Roche, and UCB, Consultant for: AbbVie, BMS, Pfizer, Merck, MedImmune, UCB, and Roche, Speakers bureau: AbbVie, BMS, Pfizer, Merck, UCB, and Roche, P. Hrycaj: None declared, C. Pacheco-Tena Consultant for: BMS, Janssen, Pfizer, Roche, and UCB, H. van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, E. Mangan Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, Y. Lin Shareholder of: Sanofi, Employee of: Sanofi, D. Bauer Shareholder of: Sanofi, Employee of: Sanofi, J. Fay Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. Parrino Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, A. Kivitz Shareholder of: Sanofi and Regeneron Pharmaceuticals, Inc., Consultant for: Sanofi, Pfizer, Roche, and UCB

Background C-EARLY (NCT01519791) assessed the efficacy and safety of certolizumab pegol (CZP)+optimized MTX vs placebo (PBO)+optimized MTX in inducing and maintaining a sustained clinical response, and inhibiting radiographic damage, in DMARD-naive patients (pts) with active, severe, progressive RA. 1 Here, we examine the association between an inadequate response to PBO+MTX or CZP+MTX treatments at Week (Wk) 12 (lack of improvement from baseline [BL] in DAS28[ESR], DAS28[CRP] or CDAI) and corresponding response at Wk 52. Objectives To examine the association between Wk12 response and Wk52 clinical response (remission [REM]/low disease activity [LDA]) in recently diagnosed DMARD-naive pts with active, severe, progressive RA, treated with CZP+optimized MTX vs PBO+optimized MTX. Methods This multicenter, double-blind, randomized controlled trial enrolled pts who were DMARD-naive with active, severe, progressive RA ( Results The NPV of Wk12 responses were high (Table): PBO+MTX pts who did not achieve DAS28(ESR) improvements from BL ≥0.6 had 94% probability of not being in REM or LDA at Wk52. CZP+MTX pts who did not achieve DAS28(ESR) improvements from BL ≥1.2 had 93% probability of not being in REM at Wk52. NPV of changes in DAS28(CRP) and CDAI at Wk12 were less informative for predicting remission at 1yr (Table). Conclusions In early RA pts treated with optimized-dose MTX, failure to achieve a ≥0.6 DAS28(ESR) reduction from BL at Wk12 was associated with a low probability (6%) of DAS28(ESR) REM/LDA at Wk52, supporting treatment step-up at 3 months. For pts with active, severe RA with poor prognostic factors where CZP has been initiated as first-line treatment, failure to achieve a rapid decrease of 1.2 points was associated with a reduced likelihood of achieving REM (7%). These findings in DMARD-naive pts are consistent with the negative predictability outcomes for CZP in established RA. 2 References Weinblatt M. Arthritis Rheumatol 2015;67(S10); van der Heijde D. J Rheumatol 2012;39:1326–33 Acknowledgement The authors acknowledge Costello Medical Consulting, funded by UCB Pharma, for writing and editorial assistance. Disclosure of Interest X. Mariette Grant/research support from: Pfizer and GlaxoSmithKline., Consultant for: Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, UCB Pharma and Sanofi-Aventis, C. Bingham Consultant for: UCB Pharma, G.-R. Burmester Consultant for: AbbVie, MSD, Pfizer, Roche and UCB Pharma, V. Bykerk: None declared, P. Emery Consultant for: Bristol-Myers Squibb, Pfizer, MSD, AbbVie, UCB Pharma, Roche, Schering Plough, Novartis and Samsung, D. Furst Grant/research support from: Abbott, Actelion, Amgen, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, NIH, Novartis, Pfizer, Roche/Genentech and UCB Pharma, Consultant for: Abbott, Actelion, Amgen, Bristol-Myers Squibb, Biogen IDEC, Janssen, Gilead, GlaxoSmithKline, NIH, Novartis, Pfizer, Roche/Genentech and UCB Pharma, D. van der Heijde Grant/research support from: AbbVie, Amgen, AstraZeneca, Augurex, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GlaxoSmithKline, Janssen, Merck, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB Pharma and Vertex, Consultant for: AbbVie, Amgen, AstraZeneca, Augurex, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GlaxoSmithKline, Janssen, Merck, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB Pharma and Vertex, Employee of: Director of Imaging at Rheumatology BV, R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, Pfizer, Roche, UCB Pharma, Consultant for: AbbVie, Biotest, BMS, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB Pharma, Vertex, B. VanLunen Employee of: UCB Pharma, C. Arendt Employee of: UCB Pharma, M. Weinblatt Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo Bioscience and UCB Pharma, Consultant for: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Crescendo Bioscience, Lilly, MedImmune, Merck, Novartis, Pfizer, Roche and UCB Pharma

Background Rheumatoid Factors (RF) and autoantibodies against citrullinated proteins (ACPA) are part of the diagnosis of rheumatoid arthritis (RA). Unfortunately these analytes lack sensitivity especially in early phases of RA. By way of screening proteins from a human protein library of over 7,000 proteins we discovered over 20 novel citrullinated antigens targeted by ACPAs in CCP positive as well as in 5–10% of CCP negative RA patients suggesting added diagnostic potential. Objectives To challenge novel human proteins as biomarkers for early RA which exhibited reactivities in citrullinated format against early and late RA patient serum samples we set to analyze sufficiently large, new cohorts of patients with early and established RA against the candidate proteins both in their citrullinated and non-citrullinated form. We also planned to veify single antigen performance by comparison to established benchmark proteins and marketed assays. Methods 34 novel citrullinated antigens were analyzed in serum samples from independent cohorts of 300 CCP positive and 151 CCP negative patients with early RA, 100 healthy volunteers and 50 patients with established RA. All samples were analyzed in a multiplexed, bead-based array on Luminex FlexMAP3D, compared to reactivities against known citrullinated proteins (vimentin, fibrinogen, enolase) and subsequently in 3 commercially available anti-CCP-assays. Results We confirmed novel citrullinated antigens targeted by ACPAs as markers of RA. The citrullinated antigens are highly reactive compared to their non-citrullinated forms in mature RA and in CCP positive samples of patients with early RA. 4 single antigens reach high overlap to established CCP-Assays each with >75% sensitivity at 97% specificity. Increased reactivity of novel antigens was identified in up to 10% of CCP negative samples suggesting the presence of additional citrullinated epitopes not present in commercial CCP assays used in this study. Conclusions Novel citrullinated antigens discovered by large scale “omics” screening via Luminex bead based arrays were confirmed in novel samples of early and established RA, especially in CCP positive samples. Reactivity in 10% CCP negative samples suggests added diagnostic value. Disclosure of Interest P. Schulz-Knappe Employee of: Protagen AG, P. Budde Employee of: Protagen AG, A. Lueking Employee of: Protagen AG, P. Schriek Employee of: Protagen AG, H. Goehler Employee of: Protagen AG, H.-D. Zucht Employee of: Protagen AG, J. Detert: None declared, G.-R. Burmester: None declared, M. Schneider: None declared, J. Richter: None declared, S. Vordenbaumen: None declared

Background Mavrilimumab, a fully human monoclonal antibody targeting the granulocyte-macrophage colony-stimulating factor receptor-α, has demonstrated efficacy and safety in disease-modifying antirheumatic drug (DMARD)-inadequate responder (IR) patients (pts) with rheumatoid arthritis (RA). 1 Objectives Few head-to-head studies in tumor necrosis factor antagonist (aTNF)-IR assess alternative aTNFs vs. other agents; this Phase IIb exploratory study (NCT01715896) evaluates the efficacy and safety of mavrilimumab and golimumab in aTNF-IR and DMARD-IR pts. Methods This 24-week study enrolled pts with active RA (28-joint Disease Activity Score [DAS28]–C-reactive protein [CRP]/erythrocyte sedimentation rate ≥3.2); ≥4 swollen joints; inadequate response to ≥1 DMARDs and/or 1–2 aTNFs receiving concomitant methotrexate (MTX; 7.5–25.0 mg/week). Pts received subcutaneous mavrilimumab 100 mg every other week (eow), based on data from the Phase IIa study, 2 or golimumab 50 mg alternating with placebo eow. Key endpoints were ACR20/50/70 responses, DAS28–CRP 0.22 at Week 24 and safety/tolerability. Treatment estimates for mavrilimumab and golimumab are presented with standard errors. Results Pts were randomized to mavrilimumab or golimumab (1:1) (Table). Data for pts receiving mavrilimumab 100 mg eow and golimumab 50 mg at Week 24 are shown for the aTNF-IR, DMARD-IR and overall strata (Table). The most common treatment-emergent adverse events (TEAEs) for mavrilimumab 100 mg and golimumab 50 mg were nasopharyngitis (5.7%, 1.5%), headache (4.3%, 2.9%), upper respiratory tract infection (4.3%, 2.9%), viral upper respiratory tract infection (4.3%, 2.9%), and hepatic enzyme increase (4.3%, 2.9%), respectively. Related serious TEAEs were pneumocystis pneumonia (n=1) and lung disorder (n=1) [both in golimumab-treated pts]. No deaths were reported and no significant pulmonary safety signals were identified. Conclusions In this exploratory study, mavrilimumab 100 mg eow and golimumab 50 mg demonstrated efficacy and an acceptable safety profile in DMARD-IR and aTNF-IR pts. The study was not powered to demonstrate statistical significance between mavrilimumab and golimumab. As mavrilimumab 100 mg eow has previously been shown to be suboptimal compared with 150 mg eow in DMARD-IR pts (EARTH EXPLORER 1), 1 additional studies are needed to establish the benefit of a higher dose in pts with moderate to severe RA and inadequate response to aTNF agents. References Burmester G, et al. Arthritis Rheum. 2014;66:S1231 Burmester G, et al. Ann Rheum Dis. 2013;72:1445–1452 Acknowledgement Funded by MedImmune. Editorial assistance: K Alexander, QXV Comms, an Ashfield business, UK Joint senior authors: D. Close and G. Burmester Disclosure of Interest M. Weinblatt Grant/research support from: BMS, UCB, Crescendo Bioscience, Consultant for: MedImmune, Astra Zeneca, Amgen, Abbvie, BMS, Crescendo Bioscience, Lilly, Pfizer, UCB, Roche, I. McInnes Grant/research support from: Research award to University of Glasgow, Consultant for: MedImmune, Astra Zeneca, J. Kremer Shareholder of: Corrona, Grant/research support from: Abbvie, Amgen, Genentech, Lilly, Pfizer, Consultant for: Abbvie, Amgen, BMS, Genentech, Lilly, Pfizer, Employee of: Corrona, P. Miranda Grant/research support from: Clinical trials: Amgen, Medimmune, Janssen, Pfizer, Celltrion, Abbott, Sanofi, Actelion, Merck & Co, Boehringer, BMS, Consultant for: Pfizer for Etanecept (fee less than USD5000), J. Vencovský Consultant for: Pfizer, Servier, Samsumg, Eli lilley, BMS, Novartis, A. Godwood Shareholder of: AstraZeneca, Employee of: MedImmune, M. Albulescu Employee of: MedImmune, D. Close, Employee of: MedImmune, G. Burmester, Consultant for: MedImmune

Background Novel treatment options together with a treat-to-target strategy present new challenges to imaging procedures in terms of therapy monitoring. Objectives To evaluate the functional outcome measured by Health Assessment Questionnaire (HAQ) as the primary outcome in patients with early rheumatoid arthritis (RA) who were treated by standard clinical care (clinical cohort) in comparison to patients in whom treatment decisions were additionally based on musculoskeletal ultrasound (US) using the US7 score (US-cohort) in a nationwide investigator initiated study in Germany. Methods Functional (HAQ), clinical (DAS28, patient9s Visual Analogue Scale [VAS] for disease activity) and laboratory parameters (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]) were analyzed at seven different time points for a total of 18 months and compared between the two study cohorts. Treatment decision was made according to local standard of care (SOC) with a treatment goal of DAS28 Results Data of 313 patients (US-cohort [n=166], clinical cohort [n=147]) demonstrated a reduction of HAQ, DAS28, VAS and laboratory activity (ESR, CRP) to a low disease activity status 18 months after the beginning/change of antirheumatic therapy according to SOC (table 1). The results of functional and clinical outcome in both cohorts did not show significant differences. However, subgroup analysis of the US-cohort with imaging remission resulted in a significantly lower HAQ, DAS28 and VAS compared to patients not fulfilling these US remission criteria (table 1). Conclusions Treatment strategies by a treat to target approach in early RA patients reduced disease activity and improved functional outcome of HAQ irrespective of imaging guidance. However, patients with imaging remission by US exhibited a significantly better functional outcome and lower disease activity status. Accordingly, an additional ultrasound examination aiming at imaging remission should be strongly considered in clinical practice. Disclosure of Interest None declared