DAS-28-based EULAR response and HAQ improvement in rheumatoid arthritis patients switching between TNF antagonists

<p>Abstract</p> <p>Introduction</p> <p>No definitive data are available regarding the value of switching to an alternative TNF antagonist in rheumatoid arthritis patients who fail to respond to the first one. The aim of this study was to evaluate treatment response in a clinical setting based on HAQ improvement and EULAR response criteria in RA patients who were switched to a second or a third TNF antagonist due to failure with the first one.</p> <p>Methods</p> <p>This was an observational, prospective study of a cohort of 417 RA patients treated with TNF antagonists in three university hospitals in Spain between January 1999 and December 2005. A database was created at the participating centres, with well-defined operational instructions. The main outcome variables were analyzed using parametric or non-parametric tests depending on the level of measurement and distribution of each variable.</p> <p>Results</p> <p>Mean (± SD) DAS-28 on starting the first, second and third TNF antagonist was 5.9 (± 2.0), 5.1 (± 1.5) and 6.1 (± 1.1). At the end of follow-up, it decreased to 3.3 (± 1.6; Δ = -2.6; p > 0.0001), 4.2 (± 1.5; Δ = -1.1; p = 0.0001) and 5.4 (± 1.7; Δ = -0.7; p = 0.06). For the first TNF antagonist, DAS-28-based EULAR response level was good in 42% and moderate in 33% of patients. The second TNF antagonist yielded a good response in 20% and no response in 53% of patients, while the third one yielded a good response in 28% and no response in 72%. Mean baseline HAQ on starting the first, second and third TNF antagonist was 1.61, 1.52 and 1.87, respectively. At the end of follow-up, it decreased to 1.12 (Δ = -0.49; p < 0.0001), 1.31 (Δ = -0.21, p = 0.004) and 1.75 (Δ = -0.12; p = 0.1), respectively. Sixty four percent of patients had a clinically important improvement in HAQ (defined as ≥ -0.22) with the first TNF antagonist and 46% with the second.</p> <p>Conclusion</p> <p>A clinically significant effect size was seen in less than half of RA patients cycling to a second TNF antagonist.</p

Rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis who failed to respond to a single previous TNF inhibitor: SWITCH-RA, a global, observational, comparative effectiveness study.

OBJECTIVES: To compare the effectiveness of rituximab versus an alternative tumour necrosis factor (TNF) inhibitor (TNFi) in patients with rheumatoid arthritis (RA) with an inadequate response to one previous TNFi. METHODS: SWITCH-RA was a prospective, global, observational, real-life study. Patients non-responsive or intolerant to a single TNFi were enrolled ≤4 weeks after starting rituximab or a second TNFi. Primary end point: change in Disease Activity Score in 28 joints excluding patient's global health component (DAS28-3)-erythrocyte sedimentation rate (ESR) over 6 months. RESULTS: 604 patients received rituximab, and 507 an alternative TNFi as second biological therapy. Reasons for discontinuing the first TNFi were inefficacy (n=827), intolerance (n=263) and other (n=21). A total of 728 patients were available for primary end point analysis (rituximab n=405; TNFi n=323). Baseline mean (SD) DAS28-3-ESR was higher in the rituximab than the TNFi group: 5.2 (1.2) vs 4.8 (1.3); p<0.0001. Least squares mean (SE) change in DAS28-3-ESR at 6 months was significantly greater in rituximab than TNFi patients: -1.5 (0.2) vs -1.1 (0.2); p=0.007. The difference remained significant among patients discontinuing the initial TNFi because of inefficacy (-1.7 vs -1.3; p=0.017) but not intolerance (-0.7 vs -0.7; p=0.894). Seropositive patients showed significantly greater improvements in DAS28-3-ESR with rituximab than with TNFi (-1.6 (0.3) vs -1.2 (0.3); p=0.011), particularly those switching because of inefficacy (-1.9 (0.3) vs -1.5 (0.4); p=0.021). The overall incidence of adverse events was similar between the rituximab and TNFi groups. CONCLUSIONS: These real-life data indicate that, after discontinuation of an initial TNFi, switching to rituximab is associated with significantly improved clinical effectiveness compared with switching to a second TNFi. This difference was particularly evident in seropositive patients and in those switched because of inefficacy

Evaluation of anti-citrullinated filaggrin antibodies as hallmarks for the diagnosis of rheumatic diseases

Background: Anti-filaggrin antibodies (AFA) are among the most specific antibodies for rheumatoid arthritis, so procedures for their detection should be included in early biological diagnoses. AFA can be detected by indirect immunofluorescence (anti-keratin antibodies, AKA) or by new enzyme immunoassays (EIA). Their comparative performance needs to be established. Objective: To compare these technical procedures to optimise the serological diagnosis of rheumatoid arthritis. Methods: Results obtained using AKA and EIA were compared in 271 sera from 140 patients with rheumatoid arthritis at various stages, 98 patients with other autoimmune diseases, and 33 healthy subjects. EIA were successively undertaken with citrullinated linear filaggrin peptide (home made EIA) or cyclic citrullinated peptide (CCP2, commercial kits). Rheumatoid factor (RF) was assessed by EIA in all patients. Results: Anti-CCP2 kits showed the best sensitivity and specificity (65% and 96%, respectively). Among the 140 patients with rheumatoid arthritis, those with very recent disease (less than six months' duration, n = 21) were studied as a separate group. In this group, the sensitivity of anti-CCP2 kits decreased to ~50%. Nevertheless this assay remained the most accurate when compared with AKA or home made EIA using linear filaggrin peptides. The combination of anti-CCP2 and RF only slightly increased the sensitivity of the diagnosis of very early rheumatoid arthritis. Conclusions: Kits using citrullinated cyclic peptides (CCP2) were more suitable than either AKA or EIA using linear filaggrin peptides for the diagnosis of early rheumatoid disease

Usefulness of polymerase chain reaction for diagnosing Whipple&#039;s disease in rheumatology

OBJECTIVES: To determine when Tropheryma whipplei polymerase chain reaction (PCR) is appropriate in patients evaluated for rheumatological symptoms. METHODS: In a retrospective observational study done in rheumatology units of five hospitals, we assessed the clinical and radiological signs that prompted T. whipplei PCR testing between 2010 and 2014, the proportion of patients diagnosed with Whipple\u27s disease, the number of tests performed and the number of diagnoses according to the number of tests, the patterns of Whipple\u27s disease, and the treatments used. Diagnostic ascertainment was based on 1- Presence of at least one suggestive clinical finding; 2- at least one positive PCR test, and 3- a response to antibiotic therapy described by the physician as dramatic, including normalization of C Reactive Protein. RESULTS: At least one PCR test was performed in each of 267 patients. Rheumatic signs were peripheral arthralgia (n = 239, 89%), peripheral arthritis (n = 173, 65%), and inflammatory back pain (n = 85, 32%). Whipple\u27s disease was diagnosed in 13 patients (4.9%). The more frequently positive tests were saliva and stool. In the centres with no diagnoses of Whipple\u27s disease, arthritis was less common and constitutional symptoms more common. The group with Whipple\u27s disease had a higher proportion of males, older age, and greater frequency of arthritis. The annual incidence ranged across centres from 0 to 3.6/100000 inhabitants. CONCLUSION: Males aged 40-75 years with unexplained intermittent seronegative peripheral polyarthritis, including those without constitutional symptoms, should have T. whipplei PCR tests on saliva, stool and, if possible, joint fluid

BIOLOGIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS IN PSORIATIC ARTHRITIS: A REAL-WORLD COHORT OF 439 PATIENTS

Congress of the European-League-Against-Rheumatism (EULAR), Amsterdam, NETHERLANDS, JUN 13-16, 2018International audienc

Place de la radiographie standard dans l’arthrite juvénile idiopathique: recommandations conjointes des sociétés françaises de rhumatologie, de radiologie, de la société francophone de rhumatologie et de médecine interne pédiatrique

International audienc

Subcutaneous Abatacept in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis: Results From a Phase III Open-Label Study

none59Objective: To investigate the pharmacokinetics, effectiveness, and safety of subcutaneous (SC) abatacept treatment over 24 months in patients with polyarticular-course juvenile idiopathic arthritis (JIA). Methods: In this phase III, open-label, international, multicenter, single-arm study, patients with polyarticular JIA (cohort 1, ages 6–17 years and cohort 2, ages 2–5 years) in whom treatment with ≥1 disease-modifying antirheumatic drug was unsuccessful received weight-tiered SC abatacept weekly: 10 to &lt;25 kg (50 mg), 25 to &lt;50 kg (87.5 mg), ≥50 kg (125 mg). Patients who had met the JIA–American College of Rheumatology 30% improvement criteria (achieved a JIA-ACR 30 response) at month 4 were given the option to continue SC abatacept to month 24. The primary end point was the abatacept steady-state serum trough concentration (Cminss) in cohort 1 at month 4. Other outcome measures included JIA-ACR 30, 50, 70, 90, 100, and inactive disease status, the median Juvenile Arthritis Disease Activity Score in 71 joints using the C-reactive protein level (JADAS-71–CRP) over time, safety, and immunogenicity. Results: The median abatacept Cminss at month 4 (primary end point) and at month 24 was above the target therapeutic exposure (10 μg/ml) in both cohorts. The percentage of patients who had achieved JIA-ACR 30, 50, 70, 90, or 100 responses or had inactive disease responses at month 4 (intent-to-treat population) was 83.2%, 72.8%, 52.6%, 28.3%, 14.5%, and 30.1%, respectively, in cohort 1 (n&nbsp;=&nbsp;173) and 89.1%, 84.8%, 73.9%, 58.7%, 41.3%, and 50.0%, respectively, in cohort 2 (n&nbsp;= 46); the responses were maintained to month 24. The median (interquartile range) JADAS-71–CRP improved from baseline to month 4: cohort 1, from 21.0 (13.5, 30.3) to 4.6 (2.1, 9.4); cohort 2, from 18.1 (14.0, 23.1) to 2.1 (0.3, 4.4). Improvements were sustained to month 24, at which time 27 of 173 patients (cohort 1) and 11 of 22 patients (cohort 2) had achieved JADAS-71–CRP remission. No unexpected adverse events were reported; 4 of 172 patients (2.3%) in cohort 1 and 4 of 46 (8.7%) in cohort 2 developed anti-abatacept antibodies, with no clinical effects. Conclusion: Weight-stratified SC abatacept yielded target therapeutic exposures across age and weight groups, was well tolerated, and improved polyarticular JIA symptoms over 24 months.noneBrunner H.I.; Tzaribachev N.; Vega-Cornejo G.; Louw I.; Berman A.; Calvo Penades I.; Anton J.; Avila-Zapata F.; Cuttica R.; Horneff G.; Foeldvari I.; Keltsev V.; Kingsbury D.J.; Viola D.O.; Joos R.; Lauwerys B.; Paz Gastanaga M.E.; Rama M.E.; Wouters C.; Bohnsack J.; Breedt J.; Fischbach M.; Lutz T.; Minden K.; Miraval T.; Ally M.M.T.M.; Rubio-Perez N.; Solau Gervais E.; van Zyl R.; Li X.; Nys M.; Wong R.; Banerjee S.; Lovell D.J.; Martini A.; Ruperto N.; Becker M.L.; Ilowite N.T.; Dare J.A.; Morris P.K.; Beukelman T.G.; Wagner-Weiner L.; Zemel L.; Quartier P.; Kone-Paut I.; Belot A.; Gerloni V.; Ferrandiz M.; Van Rensburg D.J.; Scheibel I.M.; Goldstein-Schainberg C.; Silva C.; Terreri M.T.S.E.L.A.; Gamir M.; Burgos Vargas R.; Faugier Fuentes E.; Cimaz R.; Alessio M.; Espada G.Brunner, H. I.; Tzaribachev, N.; Vega-Cornejo, G.; Louw, I.; Berman, A.; Calvo Penades, I.; Anton, J.; Avila-Zapata, F.; Cuttica, R.; Horneff, G.; Foeldvari, I.; Keltsev, V.; Kingsbury, D. J.; Viola, D. O.; Joos, R.; Lauwerys, B.; Paz Gastanaga, M. E.; Rama, M. E.; Wouters, C.; Bohnsack, J.; Breedt, J.; Fischbach, M.; Lutz, T.; Minden, K.; Miraval, T.; Ally, M. M. T. M.; Rubio-Perez, N.; Solau Gervais, E.; van Zyl, R.; Li, X.; Nys, M.; Wong, R.; Banerjee, S.; Lovell, D. J.; Martini, A.; Ruperto, N.; Becker, M. L.; Ilowite, N. T.; Dare, J. A.; Morris, P. K.; Beukelman, T. G.; Wagner-Weiner, L.; Zemel, L.; Quartier, P.; Kone-Paut, I.; Belot, A.; Gerloni, V.; Ferrandiz, M.; Van Rensburg, D. J.; Scheibel, I. M.; Goldstein-Schainberg, C.; Silva, C.; Terreri, M. T. S. E. L. A.; Gamir, M.; Burgos Vargas, R.; Faugier Fuentes, E.; Cimaz, R.; Alessio, M.; Espada, G