49 research outputs found
Subtle changes in individual joints result in both positive and negative change scores in a patient: results from a clinical trial in patients with rheumatoid arthritis
Radiographic progression in clinical trials is assessed by interpreting changes in total radiographic joint score, and the reliability of those scores depends on an evaluation of sum scores. It is not known how consistently changes in individual joints are identified by independent readers and in independent readings. Patients and 7255 single joints from 178 patients who participated in the Trial of Etanercept and Methothrexate with Radiographic Patient Outcomes (TEMPO) trial were evaluated. Every image was independently scored twice according to the Sharp-van der Heijde method by two independent readers, so that four scores per joint were available. Absolute agreement and consistency of negative and positive erosion change scores across readers and readings were compared on a per-joint level, as well as on a per-patient level. The number of joints showing a change for erosion was very low in this trial: 691/7255 analysed joints had at least one non-zero change score out of four readings. Absolute agreement between readings was remarkably poor: only 12 joints showed a consistently positive or negative change in all four readings. Change scores in opposite directions in the same joint across independent readings were rare (25 joints). Frequency of opposite joint scores in the same patient (mixed change patterns) was reader dependent. Substantial intra and interreader disagreement in scoring change in individual joints is common. Opposite joint scores in the same patient, however, are rare and reader dependent. Notwithstanding these subtle inconsistencies on the individual joint level, the total Sharp score is a useful and discriminatory outcome measur
Level of radiographic damage and radiographic progression are determinants of physical function: a longitudinal analysis of the TEMPO trial
Comparison of different definitions to classify remission and sustained remission: 1 year TEMPO results
To assess methods to calculate achieving and sustaining remission in a double blind randomised trial in patients with RA who received etanercept, methotrexate, or an etanercept/methotrexate combination. Remission was defined as DAS <1.6, DAS28 <2.6, and ACR70 response. Sustaining remission was analysed in three ways: (a) analysis of sustained DAS remission, DAS28 remission, or ACR70 response continuously for 6 months; (b) analysis of sustained remission appraised through a continuity rewarded scoring system, which is the weighted sum of all intervals in the study in which patients are in DAS or DAS28 remission; or (c) longitudinal modelling of remission odds using generalised estimating equations. Significantly more patients treated with the etanercept/methotrexate combination reached DAS remission (37%) than those treated with either methotrexate (14%) or etanercept (18%) alone (p <0.01). Results for DAS28 and for the ACR70 response were similar. Agreement between DAS remission and DAS28 remission was good, but agreement between either of these and the ACR70 response was less. Patients in DAS or DAS28 remission had a lower level of disease activity (fewer active joints, lower ESR) than those achieving ACR70 response; the converse was seen using pain VAS. The three methods were comparable for sustainability of remission and showed significant advantage for combination therapy, which increased the number and durability of remission periods. DAS and DAS28 remission results were similar for assessing achieving and sustaining remission in RA, frequently differing from patients classified as ACR70 responders. The three methods of examining duration of remission produced comparable result
ΠΠ»ΠΎΠΊΠΈΠ·ΡΠΌΠ°Π±, ΠΌΠΎΠ½ΠΎΠΊΠ»ΠΎΠ½Π°Π»ΡΠ½ΠΎΠ΅ Π°Π½ΡΠΈΡΠ΅Π»ΠΎ ΠΊ ΠΈΠ½ΡΠ΅ΡΠ»Π΅ΠΉΠΊΠΈΠ½Ρ 6, Π² ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ Ρ ΠΌΠ΅ΡΠΎΡΡΠ΅ΠΊΡΠ°ΡΠΎΠΌ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΡΠ΅Π²ΠΌΠ°ΡΠΎΠΈΠ΄Π½ΡΠΌ Π°ΡΡΡΠΈΡΠΎΠΌ ΠΈ Π½Π΅Π°Π΄Π΅ΠΊΠ²Π°ΡΠ½ΡΠΌ ΠΊΠΎΠ½ΡΡΠΎΠ»Π΅ΠΌ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ Π½Π° ΡΠΎΠ½Π΅ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ°ΠΌΠΈ ΡΠ°ΠΊΡΠΎΡΠ° Π½Π΅ΠΊΡΠΎΠ·Π° ΠΎΠΏΡΡ ΠΎΠ»ΠΈ: ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΎΡΠ΅Π½ΠΊΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ Π² ΡΠ°Π½Π΄ΠΎΠΌΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΌ ΠΊΠΎΠ½ΡΡΠΎΠ»ΠΈΡΡΠ΅ΠΌΠΎΠΌ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ III ΡΠ°Π·Ρ
Objectives To assess the efficacy and safety of olokizumab (OKZ), a monoclonal antibody against the interleukin-6 (IL-6) cytokine, versus placebo (PBO) in patients with prior inadequate response to tumour necrosis factor inhibitors (TNFi-IRs).Methods In this 24-week multicentre, placebo-controlled, double-blind study, the patients were randomised in a 2:2:1 ratio to receive subcutaneously administered OKZ 64 mg once every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w) or PBO plus methotrexate. At week 16, the patients on PBO were randomised to receive either OKZ regime. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. Disease Activity Score 28-joint count C-reactive protein (DAS28 (CRP)) <3.2 at week 12 was the major secondary efficacy endpoint. Safety and immunogenicity were assessed.Results In 368 patients randomised, ACR20 response rates were 60.9% in OKZ q2w, 59.6% in OKZ q4w and 40.6% in PBO (p<0.01 for both comparisons). Achievement of DAS28 (CRP) <3.2 was significantly different, favouring the OKZ arms. Improvements in efficacy and patientreported outcomes were maintained throughout 24 weeks and were noted after week 16 in patients who switched from PBO.Dose-related treatment-emergent serious adverse events were 7% in OKZ q2w, 3.2% in OKZ q4w and none in the PBO group.Conclusions Direct inhibition of IL-6 with OKZ resulted in significant improvements in the signs and symptoms of rheumatoid arthritis compared with PBO in TNFi-IR patients with a similar safety profile as observed for monoclonal antibodies to the IL-6 receptor.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΠΎΡΠ΅Π½ΠΈΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΡ ΠΎΠ»ΠΎΠΊΠΈΠ·ΡΠΌΠ°Π±Π° (ΠΠΠ), ΠΌΠΎΠ½ΠΎΠΊΠ»ΠΎΠ½Π°Π»ΡΠ½ΠΎΠ³ΠΎ Π°Π½ΡΠΈΡΠ΅Π»Π° ΠΊ ΠΈΠ½ΡΠ΅ΡΠ»Π΅ΠΉΠΊΠΈΠ½Ρ (ΠΠ) 6, ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ ΠΏΠ»Π°ΡΠ΅Π±ΠΎ Ρ Π±ΠΎΠ»ΡΠ½ΡΡ
ΡΠ΅Π²ΠΌΠ°ΡΠΎΠΈΠ΄Π½ΡΠΌ Π°ΡΡΡΠΈΡΠΎΠΌ (Π Π) Ρ ΠΏΡΠ΅Π΄ΡΠ΅ΡΡΠ²ΡΡΡΠΈΠΌ Π½Π΅Π°Π΄Π΅ΠΊΠ²Π°ΡΠ½ΡΠΌ ΠΎΡΠ²Π΅ΡΠΎΠΌ Π½Π° ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΡ ΡΠ°ΠΊΡΠΎΡΠ° Π½Π΅ΠΊΡΠΎΠ·Π° ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ Π°Π»ΡΡΠ° (Π€ΠΠ Ξ± ).ΠΠ΅ΡΠΎΠ΄Ρ.Π Π΄Π°Π½Π½ΠΎΠΌ 24-Π½Π΅Π΄Π΅Π»ΡΠ½ΠΎΠΌ ΠΌΠ½ΠΎΠ³ΠΎΡΠ΅Π½ΡΡΠΎΠ²ΠΎΠΌ ΠΏΠ»Π°ΡΠ΅Π±ΠΎ-ΠΊΠΎΠ½ΡΡΠΎΠ»ΠΈΡΡΠ΅ΠΌΠΎΠΌ Π΄Π²ΠΎΠΉΠ½ΠΎΠΌ ΡΠ»Π΅ΠΏΠΎΠΌ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ ΠΏΠ°ΡΠΈΠ΅Π½ΡΡ ΡΠ°Π½Π΄ΠΎΠΌΠΈΠ·ΠΈΡΠΎΠ²Π°Π»ΠΈΡΡ Π² ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠΈ 2:2:1 Π΄Π»Ρ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΠΠ ΠΏΠΎΠ΄ΠΊΠΎΠΆΠ½ΠΎ Π² Π΄ΠΎΠ·Π΅ 64 ΠΌΠ³ 1 ΡΠ°Π· Π² 2 Π½Π΅Π΄; ΠΠΠ Π² Π΄ΠΎΠ·Π΅ 64 ΠΌΠ³ 1 ΡΠ°Π· Π² 4 Π½Π΅Π΄ Π»ΠΈΠ±ΠΎ ΠΏΠ»Π°ΡΠ΅Π±ΠΎ, Π² ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ Ρ ΠΌΠ΅ΡΠΎΡΡΠ΅ΠΊΡΠ°ΡΠΎΠΌ. ΠΠ° Π½Π΅Π΄Π΅Π»Π΅ 16 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΠΏΠΎΠ»ΡΡΠ°Π²ΡΠΈΡ
ΠΏΠ»Π°ΡΠ΅Π±ΠΎ, ΡΠ°Π½Π΄ΠΎΠΌΠΈΠ·ΠΈΡΠΎΠ²Π°Π»ΠΈ Π΄Π»Ρ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΠΠ Π² ΠΎΠ΄Π½ΠΎΠΌ ΠΈΠ· Π΄Π²ΡΡ
ΡΠ΅ΠΆΠΈΠΌΠΎΠ². ΠΠ΅ΡΠ²ΠΈΡΠ½ΠΎΠΉ ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΠΉ ΡΠΎΡΠΊΠΎΠΉ ΡΠ²Π»ΡΠ»Π°ΡΡ Π΄ΠΎΠ»Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², Ρ ΠΊΠΎΡΠΎΡΡΡ
Π±ΡΠ» Π΄ΠΎΡΡΠΈΠ³Π½ΡΡ ΠΎΡΠ²Π΅Ρ ΠΏΠΎ ACR20 (20% ΡΠ»ΡΡΡΠ΅Π½ΠΈΠ΅ ΡΠΎΠ³Π»Π°ΡΠ½ΠΎ ΠΊΡΠΈΡΠ΅ΡΠΈΡΠΌ ACR) Π½Π° Π½Π΅Π΄Π΅Π»Π΅ 12. ΠΠ°ΠΆΠ½Π΅ΠΉΡΠ΅ΠΉ ΠΈΠ· Π²ΡΠΎΡΠΈΡΠ½ΡΡ
ΠΊΠΎΠ½Π΅ΡΠ½ΡΡ
ΡΠΎΡΠ΅ΠΊ Π±ΡΠ»ΠΎ Π΄ΠΎΡΡΠΈΠΆΠ΅Π½ΠΈΠ΅ Π·Π½Π°ΡΠ΅Π½ΠΈΡ DAS28-CΠ Π <3,2 Π½Π° Π½Π΅Π΄Π΅Π»Π΅ 12. ΠΡΠΎΠ²ΠΎΠ΄ΠΈΠ»Π°ΡΡ ΠΎΡΠ΅Π½ΠΊΠ° Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ ΠΈ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π΅Π½Π½ΠΎΡΡΠΈ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π£ 368 ΡΠ°Π½Π΄ΠΎΠΌΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΡΠ°ΡΡΠΎΡΠ° ΠΎΡΠ²Π΅ΡΠ° ΠΏΠΎ ACR20 ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 60,9% Π² Π³ΡΡΠΏΠΏΠ΅ ΠΠΠ 1 ΡΠ°Π· Π² 2 Π½Π΅Π΄, 59,6% Π² Π³ΡΡΠΏΠΏΠ΅ ΠΠΠ 1 ΡΠ°Π· Π² 4 Π½Π΅Π΄ ΠΈ 40,6% Π² Π³ΡΡΠΏΠΏΠ΅ ΠΏΠ»Π°ΡΠ΅Π±ΠΎ (p<0,01 Π΄Π»Ρ ΠΎΠ±ΠΎΠΈΡ
ΡΡΠ°Π²Π½Π΅Π½ΠΈΠΉ). ΠΠ΅ΠΆΠ΄Ρ Π³ΡΡΠΏΠΏΠ°ΠΌΠΈ ΠΎΡΠΌΠ΅ΡΠ°Π»ΠΈΡΡ Π·Π½Π°ΡΠΈΠΌΡΠ΅ ΡΠ°Π·Π»ΠΈΡΠΈΡ ΠΏΠΎ ΡΠ°ΡΡΠΎΡΠ΅ Π΄ΠΎΡΡΠΈΠΆΠ΅Π½ΠΈΡ DAS28-CΠ Π <3,2 Π² ΠΏΠΎΠ»ΡΠ·Ρ Π³ΡΡΠΏΠΏ ΠΠΠ. ΠΠΎΡΡΠΈΠ³Π½ΡΡΠΎΠ΅ ΡΠ»ΡΡΡΠ΅Π½ΠΈΠ΅ ΡΠΎΡ
ΡΠ°Π½ΡΠ»ΠΎΡΡ Π½Π° ΠΏΡΠΎΡΡΠΆΠ΅Π½ΠΈΠΈ Π²ΡΠ΅Ρ
24 Π½Π΅Π΄, Π° Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΠΊΠΎΡΠΎΡΡΠΌ ΠΏΠ»Π°ΡΠ΅Π±ΠΎ Π·Π°ΠΌΠ΅Π½ΡΠ»ΠΎΡΡ Π½Π° ΠΠΠ, ΡΠ»ΡΡΡΠ΅Π½ΠΈΠ΅ Π²ΡΡΠ²Π»ΡΠ»ΠΎΡΡ ΠΏΠΎΡΠ»Π΅ Π½Π΅Π΄Π΅Π»ΠΈ 16. Π§Π°ΡΡΠΎΡΠ° ΡΠ²ΡΠ·Π°Π½Π½ΡΡ
Ρ ΡΠ΅ΡΠ°ΠΏΠΈΠ΅ΠΉ ΡΠ΅ΡΡΠ΅Π·Π½ΡΡ
Π½Π΅ΠΆΠ΅Π»Π°ΡΠ΅Π»ΡΠ½ΡΡ
ΡΠ²Π»Π΅Π½ΠΈΠΉ ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 7% Π² Π³ΡΡΠΏΠΏΠ΅ ΠΠΠ 1 ΡΠ°Π· Π² 2 Π½Π΅Π΄ ΠΈ 3,2% Π² Π³ΡΡΠΏΠΏΠ΅ ΠΠΠ 1 ΡΠ°Π· Π² 4 Π½Π΅Π΄, Π² ΡΠΎ Π²ΡΠ΅ΠΌΡ ΠΊΠ°ΠΊ Π² Π³ΡΡΠΏΠΏΠ΅ ΠΏΠ»Π°ΡΠ΅Π±ΠΎ ΠΈΡ
Π½Π΅ Π±ΡΠ»ΠΎ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΡΡΠΌΠΎΠ΅ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΠ6 ΠΠΠ ΠΏΡΠΈΠ²Π΅Π»ΠΎ ΠΊ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠΌΡ ΡΠΌΠ΅Π½ΡΡΠ΅Π½ΠΈΡ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΠΎΡΡΠΈ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠΉ Π Π ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ ΠΏΠ»Π°ΡΠ΅Π±ΠΎ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π½Π΅Π°Π΄Π΅ΠΊΠ²Π°ΡΠ½ΡΠΌ ΠΎΡΠ²Π΅ΡΠΎΠΌ Π½Π° ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΡ Π€ΠΠ Ξ± , ΠΏΡΠΈ ΡΡΠΎΠΌ ΠΏΡΠΎΡΠΈΠ»Ρ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ Π±ΡΠ» ΡΡ
ΠΎΠΆ Ρ ΡΠ°ΠΊΠΎΠ²ΡΠΌ ΠΏΡΠΈ Π½Π°Π·Π½Π°ΡΠ΅Π½ΠΈΠΈ ΠΌΠΎΠ½ΠΎΠΊΠ»ΠΎΠ½Π°Π»ΡΠ½ΡΡ
Π°Π½ΡΠΈΡΠ΅Π» ΠΊ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΡ ΠΠ6
Nitration of the Pollen Allergen Bet v 1.0101 Enhances the Presentation of Bet v 1-Derived Peptides by HLA-DR on Human Dendritic Cells
Nitration of pollen derived allergens can occur by NO2 and ozone in polluted air and it has already been shown that nitrated major birch (Betula verrucosa) pollen allergen Bet v 1.0101 (Bet v 1) exhibits an increased potency to trigger an immune response. However, the mechanisms by which nitration might contribute to the induction of allergy are still unknown. In this study, we assessed the effect of chemically induced nitration of Bet v 1 on the generation of HLA-DR associated peptides. Human dendritic cells were loaded with unmodified Bet v 1 or nitrated Bet v 1, and the naturally processed HLA-DR associated peptides were subsequently identified by liquid chromatography-mass spectrometry. Nitration of Bet v 1 resulted in enhanced presentation of allergen-derived HLA-DR-associated peptides. Both the copy number of Bet v 1 derived peptides as well as the number of nested clusters was increased. Our study shows that nitration of Bet v 1 alters antigen processing and presentation via HLA-DR, by enhancing both the quality and the quantity of the Bet v 1-specific peptide repertoire. These findings indicate that air pollution can contribute to allergic diseases and might also shed light on the analogous events concerning the nitration of self-proteins
Regulatory T cells and their role in rheumatic diseases: a potential target for novel therapeutic development
Regulatory T cells have an important role in limiting immune reactions and are essential regulators of self-tolerance. Among them, CD4+CD25high regulatory T cells are the best-described subset. In this article, we summarize current knowledge on the phenotype, function, and development of CD4+CD25high regulatory T cells. We also review the literature on the role of these T cells in rheumatic diseases and discuss the potential for their use in immunotherapy