Reproducibility of pulmonary function tests in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a rare autoimmune disease in which interstitial lung disease (ILD) is the leading cause of morbidity and mortality. Clinical management of the lung disease is mainly based on pulmonary function testing (PFT) and their changes over time. Little is known about the reproducibility of PFT testing in SSc patients. The aim of this study was to assess the test-retest reliability and reproducibility of PFTs in SSc patients with or without ILD over 30 days in order determine the potential physiologic variation over the time. We performed prospective observational study of SSc patients. The FVC, FEV1/FVC ratio, DLCO and KCO parameters were assessed in this population at four different timepoints; T0 (time 0) and H3 (T0 + 3 h) defined test-retest reliability, D15 (T0 + 15 days) and D30 (T0 + 30 days) for reproducibility. A mixed linear model was used to test the effect of time (and therefore reproducibility) on patients and we looked for an interaction. We included 25 SSc patients divided in two groups, 14 with ILD and 11 non-ILD. Interactions between time and group were not significant and were not reported. Time and group did not significantly influence the different measures of the PFT: FVC [p values time and group effect respectively (0.33; 0.34)], FEV1/FVC ratio (0.093; 0.056) and DLCO (0.99; 0.13) in the ILD and non ILD group (Table S2). The analyse with interactions between time and group were not significant and are not reported. We also used a Bland Altman test to assess reproducibility for FVC (L) and DLCO (mMKpa/min/L), Figs. 1 and 2 respectively. The measurements were therefore reproducible over time and in each group. PFT parameters are reproducible over time in a clinically stable population of SSc (no significant effect of the time T0, H3, D15 and D30) and there is no significant distinction between patients with ILD and no ILD. These respiratory functional data can further underline their use in clinical practice.

[Bilateral periostitis and arthritis: about a case of hypertrophic osteoarthropathy]. / Périostite bilatérale et polyarthrite : à propos d'un cas d'ostéoarthropathie hypertrophique pneumique.

We report the case of a 67-year-old female patient presenting swelling of the hands and feet and pain in both legs. Clinical examination and bone scintigraphy identify the triad "digital clubbing - arthritis - bilateral periostitis of the long bones", leading to a diagnosis of hypertrophic osteoarthropathy, a syndrome usually associated with pulmonary neoplasia. The thoracic CT-scan, followed by a biopsy, effectively diagnosed a right upper lobe adenocarcinoma. Surgical treatment of the neoplasia allowed the resolution of the clinical complaints and the pathological scintigraphic findings.

Nous rapportons le cas d'une patiente de 67 ans présentant des gonflements des mains et des pieds ainsi que des douleurs des deux jambes. L'examen clinique et la scintigraphie osseuse identifient la triade «hippocratisme digital - arthrites - périostite bilatérale des os longs¼, permettant de poser un diagnostic d'ostéoarthropathie hypertrophique, un syndrome habituellement associé à une néoplasie pulmonaire. Le scanner thoracique, suivi d'une biopsie, ont en effet diagnostiqué un adénocarcinome localisé au niveau du lobe supérieur droit. La prise en charge chirurgicale de la néoplasie a permis la résolution des plaintes cliniques et de l'aspect scintigraphique pathologique.

[Life-threatening flare of an underlying «paraneoplastic¼ dermatomyositis in a patient with lung adenocarcinoma treated with anti-PD-1 pembrolizuma]. / Poussée sévère d'une dermatomyosite pré-existante chez une patiente avec un adénocarcinome pulmonaire traité par pembrolizumab, un anti-PD-1.

Dermatomyositis is an autoimmune disease mainly characterized by muscle and skin involvement. Its association with cancer is known but the term «paraneoplastic¼ remains debated. We report here the case of a 71-year-old woman with a new diagnosis of dermatomyositis with, at the same time, the discovery of a lung adenocarcinoma. Lung cancer was treated with pembrolizumab, an immune checkpoint inhibitor directed against the "Programmed cell Death protein 1" (PD-1) receptor. Three weeks later, the patient presented a severe flare of dermatomyositis. Administration of intravenous corticosteroids and infliximab were ineffective. Intravenous immunoglobulins were then administered, followed by subcutaneous methotrexate, with a progressive positive evolution. Flares of pre-existing autoimmune diseases are observed under immune check point inhibitors, even when the evolution of the cancer is favourable. These immune-related adverse events are often «mild to moderate¼ and severe immune related side effects are not more frequent when the patient has a pre-existing autoimmune disease. Treatment can be maintained in the majority of cases. However, as demonstrated in this clinical case, although immune checkpoint inhibitors are not contraindicated in autoimmune diseases, the presence of myositis requires special attention given the potential severity of flares.

: La dermatomyosite est une maladie auto-immune principalement caractérisée par une atteinte musculaire et cutanée. Son association avec le cancer est connue, mais le terme «paranéoplasique¼ reste débattu. Nous rapportons ici le cas d'une patiente de 71 ans avec un nouveau diagnostic de dermatomyosite et, au même moment, la découverte d'un adénocarcinome pulmonaire. La néoplasie pulmonaire a été traitée par pembrolizumab, un inhibiteur des points de contrôle immunitaire dirigé contre le récepteur «Programmed cell Death protein 1¼ (PD-1). Trois semaines plus tard, la patiente présentera une poussée sévère de dermatomyosite, ne répondant pas à la corticothérapie intraveineuse ni à l'infliximab. Des immunoglobulines intraveineuses sont alors administrées, suivies de méthotrexate sous-cutané, avec une évolution progressivement positive. On observe des poussées de maladies auto-immunes préexistantes sous inhibiteurs de points de contrôle immunitaire, même quand l'évolution néoplasique est favorable. Ces effets secondaires immuno-induits sont souvent «légers à modérés¼ et on n'observe pas plus de manifestations indésirables «sévères¼ lorsque le patient présente une maladie auto-immune pré-existante. Le traitement peut être maintenu dans la majorité des cas. Toutefois, comme démontré dans ce cas clinique, bien que les inhibiteurs de points de contrôle immunitaire ne soient pas contre-indiqués en cas de maladie auto-immune, la présence d'une myosite nécessite une attention particulière vu la gravité potentielle des poussées.

[About a pediatric patients cohort followed in the adult rheumatology department of CHU Liège]. / À propos d'une cohorte de jeunes patients suivis dans le service de rhumatologie adulte du CHU de Liège.

We realized an observational retrospective study about pediatric patients (between 1 to 18 years) followed at the CHU Liège in an adult rheumatologic service during the last 14 years. This study identified 102 patients who developed the first symptoms during infancy, identifying 39 different diseases. Mainly, we identify cases of idiopathic juvenile arthritis, rheumatoid arthritis, spondylarthropathies, systemic lupus erythematosus, systemic vasculitis, connective tissue diseases, bone diseases, and phosphocalcic metabolic disorders. These observations highlight the difficulties to classify inflammatory articular diseases in young patients. Furthermore, this article may be helpful to identify some specificities in the pediatric population who suffers from rheumatologic diseases and some essential factors to make an optimal transition to adult medicine.

Nous avons réalisé une étude rétrospective observationnelle sur les patients d'âge pédiatrique (1-18 ans) ayant été vus en rhumatologie adulte au CHU de Liège ces 14 dernières années. Cette étude a permis d'identifier 102 patients présentant une pathologie rhumatologique à début pédiatrique pour lesquels 39 diagnostics différents ont été retenus. On retrouve principalement des arthrites juvéniles idiopathiques, mais également des polyarthrites rhumatoïdes, des spondylarthropathies, des lupus érythémateux systémiques, des vascularites systémiques, des pathologies du tissu conjonctif, des pathologies osseuses, ainsi que des troubles du métabolisme phosphocalcique. Ces observations mettent en lumière les difficultés de classification de certaines pathologies articulaires inflammatoires du jeune adulte. Elles permettent également d'identifier les spécificités pédiatriques de ces pathologies rhumatologiques et les éléments essentiels à la réalisation d'une transition optimale vers la médecine adulte.

Inflammatory profile of induced sputum composition in systemic sclerosis and comparison with healthy volunteers.

Systemic sclerosis (SSc) is a potentially serious and disabling connective tissue disease specially in case of interstitial lung disease (SSc-ILD). The aim of our study was to evaluate the potential utility of dosing in the induced sputum (IS) and to compare their levels in SSc-ILD and SSc-nonILD patients, as well as in healthy volunteers (HV). IS and sera values were also compared. In a prospective cross-sectional analysis, we studied the IS and serum provided from 25 SSc patients, 15 SSc-nonILD and 10 SSc-ILD, compared to 25 HV. We analyzed sputum cell composition and quantified in the supernatant and corresponding serum by commercially available immunoassays: IGFBP-1, IGFBP-2, IGFBP-3, TGF-ß, IL-8, TNF-α, YKL-40, MMP-7 and MMP-9. Lung function was studied by the determination of FEV-1 (%), FVC (%), DLCO (%) and KCO (%). The IS of SSc patients had a lower weight than HV (p<0.05, p<0.01) without any significant difference with regard to the cellularity. IGFBP-1 (p < 0.0001), TGF-ß (p < 0.05), IL-8 (p < 0.05), YKL-40 (p < 0.0001) and MMP-7 (p < 0.01) levels were increased in the IS of SSc patients compared to HV. Only IL-8 serum levels (p < 0.001) were increased in SSc patients compared to HV. Neither in IS nor in serum were observed differences between SSc-ILD and SSc-nonILD patients. Correlations were observed between IS IL-8 levels and FEV-1 (%) (r = = - 0.53, p < 0.01), FVC (%) (r = - 0.51, p < 0.01) and annualized ∆KCO (%) (r = 0.57, p < 0.05), between IS TGF-ß levels and annualized ∆FEV-1 (%) (r = = - 0.57, p < 0.05), between IS IGFBP-2 levels and annualized ∆KCO (%) (r = 0.56, p < 0.05). Our study showed that SSc patients exhibit raised IS levels of IGFBP-1, TGF-ß, IL-8, YKL-40 and MMP-7, molecules known to be involved in lung remodeling and fibrotic process, without any significant difference between SSc-ILD and SSc-nonILD patients. IL-8, TGF-ß and IGFBP-2 are correlated with lung function in SSc patients which emphasize clinical relevance. IS analysis represents a new approach to understand lung inflammatory process in SSc patients. A longitudinal study is needed to evaluate their pathophysiological relevance.

[Remarkable medical advances in rheumatology : may be ]. / Une révolution thérapeutique en rhumatologie : oui, mais .

The development of new drugs is a significant activity in a university hospital that favors access to therapeutic novelties to patients. Rheumatology, whose drug armamentarium was poor in the 1980s, has benefited from the huge progresses of immunology in the 1980-1990s, allowing a therapeutic revolution in whom the academic hospital of Liège (CHU Liège) has been strongly implicated. First protocols with anti-TNF-? monoclonal antibodies have been applied in 1997. Sixty-one protocols have been initiated in rheumatoid arthritis, 12 in ankylosing spondylitis, 10 in psoriatic arthritis, 9 in systemic erythematosus lupus, 3 in giant cell arteritis, 1 in polymyalgia rheumatica, 5 in osteoarthritis and 4 in osteoporosis. Potential and pitfalls will be discussed disease by disease and also by drug categories. The balance remains globally positive, but remission is far from be reached.

La recherche clinique médicamenteuse est une activité importante dans un hôpital universitaire. Elle valide des nouveautés thérapeutiques et fait bénéficier les patients de traitements novateurs bien avant leur mise sur le marché. La rhumatologie est une discipline dont l'arsenal thérapeutique était pauvre dans les années 1980, et les immenses progrès de l'immunologie, réalisés entre 1980 et 1995, lui ont permis de vivre une véritable révolution thérapeutique à laquelle notre service a amplement participé. C'est en 1997 que les premiers traitements par anticorps monoclonaux anti-TNF-? (les traitements dits biologiques) ont été utilisés au CHU de Liège. Soixante et une études seront initiées dans la polyarthrite rhumatoïde, 12 dans la spondylarthrite ankylosante, 10 dans la polyarthrite psoriasique, 9 dans le lupus érythémateux disséminé, 3 dans l'artérite temporale de Horton, une dans la pseudopolyarthrite rhizomélique, une dans la sclérodermie, 5 dans l'arthrose, 4 dans l'ostéoporose. Les espoirs et les déceptions observées dans les différentes indications, et avec les différentes molécules, sont analysées. Le bilan est globalement positif, mais les résultats encore insuffisants que pour arriver au concept de rémission.

Up to 5-year retention of abatacept in Belgian patients with moderate-to-severe rheumatoid arthritis: a sub-analysis of the international, observational ACTION study.

Favorable efficacy and safety profiles have been demonstrated for abatacept in patients with rheumatoid arthritis (RA) in randomized controlled trials, but these data require validation during long-term follow-ups in routine clinical practice. This study explored long-term safety and retention rates in RA patients treated with intravenous abatacept in the Belgian cohort of the international AbataCepT In rOutiNe clinical practice (ACTION) study (NCT02109666). This non-interventional, observational, longitudinal study included Belgian patients aged ≥ 18 years with moderate-to-severe RA who started intravenous abatacept treatment as first- or second/further-line biologic therapy in routine clinical practice. Between October 2010 and December 2012, 141 patients were enrolled in this cohort, of whom 135 evaluable patients (6 biologic-naïve; 129 previously exposed to ≥ 1 prior biologic disease modifying anti-rheumatic drugs) were eligible for the descriptive analysis; 131/135 were included in the effectiveness analysis. Mean disease duration was 10.5 years (standard deviation 9.7) before abatacept initiation. RA patients presented with high disease activity and comorbidity rate, having failed multiple previous treatment options. In this cohort, the 5-year abatacept retention rate was 34% (95% confidence interval, 23-45%) per protocol, and 51% (95% confidence interval, 40-61%) when temporary discontinuations of abatacept > 84 days (n = 24) were not considered as treatment discontinuations. After 5 years of abatacept treatment, clinical outcomes were favorable [good/moderate European League Against Rheumatism (EULAR) responses in 91.7% patients]. No new safety signals were detected for abatacept in routine clinical practice. In this difficult-to-treat Belgian RA population, high retention rates, good clinical outcomes and favorable safety profile were observed with abatacept.

Bio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: a double-blind multicenter randomized placebo controlled three-arm study.

OBJECTIVES: Comparison of two doses of bio-optimized Curcuma longa extract (BCL) in the management of symptomatic knee osteoarthritis (OA). METHODS: A prospective, randomized, 3-month, double-blind, multicenter, three-group, placebo-controlled trial assessing Patient Global Assessment of Disease Activity (PGADA) and serum sColl2-1, a biomarker of cartilage degradation, as co-primary endpoints. Pain on visual analog scale (VAS), Knee injury and Osteoarthritis Outcome Score (KOOS), and paracetamol/non-steroidal anti-inflammatory drug (NSAID) consumption were used as secondary endpoints. RESULTS: One hundred fifty patients with knee OA were followed for 90 days. Low and high doses of BCL showed a greater decrease of PGADA than placebo. Analysis of sColl2-1 showed in the placebo and BCL low-dose groups, but not in the BCL high-dose group, a transient but non-significant increase of sColl2-1 between T0 and T1. Thereafter, in all groups, sColl2-1 decreased between T1 and T3 (all p < 0.01), but no difference between the groups was found. Pain reduction at day 90 in the low- and high-dose BCL groups (- 29.5 mm and - 36.5 mm) was higher than that in the placebo (- 8 mm; p = 0.018). The global KOOS significantly decreased overtime, but changes were comparable across treatment arms. The ratio of patients with adverse events (AE) related to the product was similar in the placebo and treatment groups, but the number of AE linked to the product was higher in the high-dose BCL group compared to the placebo (p = 0.012). CONCLUSIONS: BCL appeared safe and well-tolerated with no evidence of severe adverse effects. Efficacy analysis suggested positive trends for measurements of PGADA and serum levels of an OA biomarker and showed a rapid and significant decrease of pain in knee OA (Trial registration: ISRCTN, ISRCTN12345678. Registered 21 September 2016-retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02909621?term=osteoarthritis+curcumin&rank=5-Evaluation of FLEXOFYTOL® Versus PLACEBO (COPRA) NCT02909621).

Restriction of spontaneous and prednisolone-induced leptin production to dedifferentiated state in human hip OA chondrocytes: role of Smad1 and ß-catenin activation.

OBJECTIVE: The aetiology of OA is not fully understood although several adipokines such as leptin are known mediators of disease progression. Since leptin levels were increased in synovial fluid compared to serum in OA patients, it was suggested that joint cells themselves could produce leptin. However, exact mechanisms underlying leptin production by chondrocytes are poorly understood. Nevertheless, prednisolone, although displaying powerful anti-inflammatory properties has been recently reported to be potent stimulator of leptin and its receptor in OA synovial fibroblasts. Therefore, we investigated, in vitro, spontaneous and prednisolone-induced leptin production in OA chondrocytes, focusing on transforming growth factor-ß (TGFß) and Wnt/ß-catenin pathways. DESIGN: We used an in vitro dedifferentiation model, comparing human freshly isolated hip OA chondrocytes cultivated in monolayer during 1 day (type II, COL2A1 +; type X, COL10A1 + and type I collagen, COL1A1 -) or 14 days (COL2A1 -; COL10A1 - and COL1A1+). RESULTS: Leptin expression was not detected in day1 OA chondrocytes whereas day14 OA chondrocytes produced leptin, significantly increased with prednisolone. Activin receptor-like kinase 1 (ALK1)/ALK5 ratio was shifted during dedifferentiation, from high ALK5 and phospho (p)-Smad2 expression at day1 to high ALK1, endoglin and p-Smad1/5 expression at day14. Moreover, inactive glycogen synthase kinase 3 (GSK3) and active ß-catenin were only found in dedifferentiated OA chondrocytes. Smad1 and ß-catenin but not endoglin stable lentiviral silencing led to a significant decrease in leptin production by dedifferentiated OA chondrocytes. CONCLUSIONS: Only dedifferentiated OA chondrocytes produced leptin. Prednisolone markedly enhanced leptin production, which involved Smad1 and ß-catenin activation.

[Clinical case of the month. A rare case of arthritis and fever]. / Un cas rare d'arthrite fébrile.

We present the case report ofa 28 year old male presenting with recurrent fever episodes and arthralgia. Based on the presence of an inflammatory syndrome, a hyperferritinemia, a salmon-pink rash and recurrent fever episodes, the diagnosis of an adult onset Still's disease (AOSD) was made. A treatment with corticosteroids was started. During the following years, the corticosteroids could not be tapered. Eventually, a treatment with anakinra, an interleukin 1 (IL-1) receptor antagonist was started, allowing tapering of the corticosteroids. This case report supports the possible role of IL-1 in the pathogenesis ofAOSD, possibly through the inflammasome.

[The management of systemic lupus erythematosus with biological therapies]. / Traitement du lupus érythémateux dissémine par les médicaments biologiques.

The efficacy and safety of targeted biological therapies have been analyzed in patients suffering from systemic lupus erythematosus. In renal lupus, infliximab has shown prolonged improvement of the renal function after the induction period (small open studies), whereas abatacept had no significant efficacy (randomised controlled study). In renal and non renal lupus, rituximab did not confirm its efficacy in two randomised controlled studies. In non renal lupus, epratuzumab has shown efficacy in a phase IIb. Belimumab at the high posology of 10 mg/kg has also shown significant efficacy in two large randomised controlled studies.

[Rhupus: when rheumatoid arthritis meets lupus]. / Le rhupus: à la frontière entre polyarthrite rhumatoïde et lupus érythémateux disséminé.

There exists diseases in rheumatology fulfilling classification criteria for either rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). They are called "rhupus". We retrospectively analyzed the data base "GLIMS" of the CHU de Liège from the starting date of november 2005 until april 2011 to identified those patients that were positive for the anti-sDNA antibody marker of SLE and for the anti-CCP antibody, marker of RA. Fourteen patients were identified and two other patients were added, one suffering from SLE, and the other from RA, and likely to be rhupus. Of the 16 patients analyzed, 9 were real RA with anti-dsDNA antibodies induced by anti-TNF-alpha therapies. Seven were candidates to be rhupus and 6 were retained. They were all women, with a median age of 51 years and in addition were all anti-SS-A antibody positive.

[Genetic and environmental interactions on the development of rheumatoid arthritis]. / Interactions de la génétique et de l'environnement sur le développement de la polyarthrite rhumatoïde.

Rheumatoid arthritis (RA) more and more becomes a syndrome, rather than a disease, with genetic, hormonal and environmental influences, among which smoking and the microbiota generate focused interest. The shared epitope and PTPN22 loci are associated with RA, and, particularly, with the "classical" form with anti-citrullinated peptide antibodies (ACPA) and IgM-rheumatoid factor (IgM-RF) positivity. Pregnancy is associated with a--temporary--remission of RA. Epidemiological studies have shown that oral contraception, parity and hormonal replacement therapy influence the severity of RA, and, this is still discussed, its incidence. Smoking is the first environmental factor strongly associated with RA, specifically with the shared epitope and with ACPA. The study of the microbiota is a novel emerging field that will help us to better understand patterns and evolution of RA.

[Targeted therapy in inflammatory disease: cytokines]. / Thérapies ciblées en rhumatologie: les cytokines.

Summarizing 15 years of therapeutic development of a discipline into a few lines is not an easy thing to do. There are many potential targets involved in the inflammatory of auto-immune diseases. Due to the development of biotherapies the choice has become larger, and it is now possible to target practically any molecule (cytokine, chemokine or surface receptor for example). Cytokines represent the first example of therapeutic target that played a major role in the revolution of our discipline. The first part of presentation will focus on the pro-inflammatory cytokines (TNFalpha, and interleukines 1 and 6). We shall then, detail the development of a new cytokinic target: BLyS (B lymphocyte stimulator) whose role in the autoimmune diseases appeared recently.

[Early referral of first line patients suspected of axial spondyloarthritis: the Belgian results of the RADAR study]. / Renvoi précoce au spécialiste de patients avec une suspicion de spondyloarthropathie axiale en première ligne: les résultats belges de l'étude RADAR.

Currently, there is a 5 to 7 years gap between the first symptoms and the diagnosis of ankylosing spondylitis. A better patient referral might reduce this gap and accelerate the adequate treatment implementation. The study objective was to compare 2 referral strategies used in first line. In Belgium, 208 referral physicians assigned to 16 rheumatology centres were randomized to refer chronic back pain patients (with onset <45 years) using 1 of the 2 referral strategies: Strategy 1 :1 of 3 criteria (inflammatory back pain, HLA-B27, sacroiliitis on imaging); or Strategy 2: 2 of6 criteria (IBP inflammatory back pain, HLA-B27, sacroiliitis, family history, good response to NSAIDs, extra-articular manifestations). Among the 141 referred patients with strategy 1 and 2, 26.0 and 36.9% respectively were diagnosed with Axial Spondylarthritis (SpA). Inflammatory back pain, sacroiliitis and good respond to NSAIDs were the most frequently used criteria (92.9 %, 36.2 % and 33.3% respectively). This study emphasizes the high prevalence of undiagnosed axial SpA in patients with chronic back pain and stressed the necessity to increase awareness of the disease.

Assessment of long-term safety and efficacy of etanercept in a 5-year extension study in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate long-term safety and efficacy of etanercept (ETN) in patients with rheumatoid arthritis (RA) without concomitant disease-modifying antirheumatic drug therapy. METHODS: A total of 549 patients enrolled in this 5-year, open-label extension after completing 1 of 2 randomised controlled studies; all patients received ETN 25 mg twice weekly during the extension. Safety assessments included physical exams, adverse events (AEs), vital signs, laboratory tests, and autoantibody evaluations. Key efficacy endpoints included numbers of responders achieving the American College of Rheumatology (ACR) criteria, low disease activity scores, and disease remission. RESULTS: Three hundred and eight (56%) patients completed the 5-year extension study. Total ETN exposure, including that received during the double-blind studies was 2212 patient-years. Withdrawals for efficacy- and safety-related reasons were 12% and 19%, respectively. The most common AE was upper respiratory infection (44%). Rates of serious infections decreased over the 5-year period; one case of suspected tuberculosis was reported. Rates of malignancies remained generally consistent during the 5-year period. There were no reports of demyelinating disease, serious blood dyscrasias, or opportunistic infections. The relationship between autoantibody titres and clinical events was not statistically significant. Less than 5% of patients tested positive for anti-etanercept antibodies and all antibodies were non-neutralising. After 5 years, ACR 20, 50, and 70 response rates were 78%, 51%, and 32%, respectively; the mean percentage of patients achieving low disease activity score (DAS ≤ 2.4) and remission (DAS ≤ 1.6) were 44% and 20%, respectively. CONCLUSIONS: ETN maintained a favourable safety profile and consistent efficacy throughout the 5-year study duration.