Progression Of Joint Damage Research Articles

Tofacitinib versus Methotrexate in Rheumatoid Arthritis

BackgroundMethotrexate is the most frequently used first-line antirheumatic drug. We report the findings of a phase 3 study of monotherapy with tofacitinib, an oral Janus kinase inhibitor, as compared with methotrexate monotherapy in patients with rheumatoid arthritis who had not previously received methotrexate or therapeutic doses of methotrexate.MethodsWe randomly assigned 958 patients to receive 5 mg or 10 mg of tofacitinib twice daily or methotrexate at a dose that was incrementally increased to 20 mg per week over 8 weeks; 956 patients received a study drug. The coprimary end points at month 6 were the mean change from baseline in the van der Heijde modified total Sharp score (which ranges from 0 to 448, with higher scores indicating greater structural joint damage) and the proportion of patients with an American College of Rheumatology (ACR) 70 response (≥70% reduction in the number of both tender and swollen joints and ≥70% improvement in three of five other criteria: the patient's assessment of pain, level of disability, C-reactive protein level or erythrocyte sedimentation rate, global assessment of disease by the patient, and global assessment of disease by the physician).ResultsMean changes in the modified total Sharp score from baseline to month 6 were significantly smaller in the tofacitinib groups than in the methotrexate group, but changes were modest in all three groups (0.2 points in the 5-mg tofacitinib group and <0.1 point in the 10-mg tofacitinib group, as compared with 0.8 points in the methotrexate group [P<0.001 for both comparisons]). Among the patients receiving tofacitinib, 25.5% in the 5-mg group and 37.7% in the 10-mg group had an ACR 70 response at month 6, as compared with 12.0% of patients in the methotrexate group (P<0.001 for both comparisons). Herpes zoster developed in 31 of 770 patients who received tofacitinib (4.0%) and in 2 of 186 patients who received methotrexate (1.1%). Confirmed cases of cancer (including three cases of lymphoma) developed in 5 patients who received tofacitinib and in 1 patient who received methotrexate. Tofacitinib was associated with increases in creatinine levels and in low-density and high-density lipoprotein cholesterol levels.ConclusionsIn patients who had not previously received methotrexate or therapeutic doses of methotrexate, tofacitinib monotherapy was superior to methotrexate in reducing signs and symptoms of rheumatoid arthritis and inhibiting the progression of structural joint damage. The benefits of tofacitinib need to be considered in the context of the risks of adverse events. (Funded by Pfizer; ORAL Start ClinicalTrials.gov number, NCT01039688.)

SPP1 rs9138 variant contributes to the severity of radiological damage in anti-citrullinated protein autoantibody-negative rheumatoid arthritis

ObjectiveWe recently reported an association of the SPP1 rs9138 and rs11439060 functional variants with the risk of rheumatoid arthritis (RA), the association being greater in anti-citrullinated protein autoantibody (ACPA)-negative patients....

Reproducibility analysis of knee circumference in individuals with osteoarthritis

Knee osteoarthritis presents pain, loss of function, and joint swelling as its main symptoms. The joint swelling is defined as an accumulation of fluid in the joint due to the inflammatory process that contributes to progressive joint damage; it causes limitation in the range of knee motion, decreases proprioception, and affects the functional capacity and the quality of life of the individual. The measurement of articular cartilage volume is essential in clinical practice. The measurement of knee circumference using a measuring tape is a widely used, inexpensive, and accessible technique. However, as it is considered subjective, there is no evidence to support its use. Objective: To examine the reproducibility of this technique in patients with knee osteoarthritis. Method: Participants underwent two evaluations performed by two independent raters, at different times. The measurement of knee circumference was performed using a measuring tape 150 cm in length, taking as reference the superior pole of the patella. Results: The knee circumferences of 114 individuals were measured. According to the intraclass correlation coefficient (ICC), we observed a strong correlation (ICC = 0.98) between raters. Conclusion: The use of a measuring tape as a resource to measure knee circumference in individuals with osteoarthritis is a reliable and reproducible method.

THU0158 Inhibition of Radiographic Progression and Its Association with Clinical Parameters in RA Patients Treated with CT-P13 and Innovator Infliximab in PLANETRA Study

BackgroundCT-P13 is a biosimilar of innovator infliximab (INX), approved by the European Medicines Agency in 2013. Clinical data up to 1 year from PLANETRA have been reported at EULAR 20131ObjectivesTo...

THU0455 Transcriptomics to Identify Synovial Genes and Pathways Associated with Disease Progression in A Cohort of Early Osteoarthritis Patients (CHECK)

BackgroundIf and how the synovial activation that is observed in over 50% of osteoarthritis (OA) patients contributes to irreversible joint pathology, is not known.ObjectivesTo identify pathways that may determine progression...

SAT0041 14-3-3Eta Predicts Radiographic Progression in Recent-Onset Polyarthritis Patients

BackgroundEarly RA diagnosis and timely treatment can improve patient outcomes. Markers are needed to identify patients with early disease who are at high-risk of joint damage progression. Current clinical and...

SAT0214 Statistical Evalution of Joint Damage Prgression in Patients with Rheumatoid Arthritis Treated with Infliximab or Biosimilar Infliximab (CT-P13) Anti-TNF Therapy: A Role of Sensitivity Analysis for Missing Data Evaluating Similarity

BackgroundBiosimilar infliximab (CT-P13) was the first monoclonal antibody biosimilar of innovator infliximab (INX) approved by the European Medicines Agency. In the PLANETRA study (1), patients with rheumatoid arthritis received 3...

AB0244 Radiographic Evaluation of Large Joint Damage in Patients with Rheumatoid Arthritis Using ARASHI Scoring Method

BackgroundStructural impairment of large joints in patients with rheumatoid arthritis (RA) is strongly associated with functional disabilities. Although evaluation methods of large joint damage were limited, the ARASHI study group...

THU0469 Genetic Variants in IL-6, IL-10, C5-TRAF1 and FCRL3 and Progression of Joint Damage in Rheumatoid Arthritis; A Study on Six Cohorts

BackgroundThanks to the introduction of novel treatments and up-to-date treatment strategies, the severity of joint destruction in rheumatoid arthritis (RA) has decreased considerably. Nonetheless, in daily clinical practice radiographic progression...

SAT0210 X-Ray and MRI Results from A Phase Iib Study of Subcutaneous Anti-Interleukin-6 Monoclonal Antibody Clazakizumab with or without MTX in Adults with Moderate-To-Severe Active RA and Inadequate Response to Conventional DMARDS Including Methotrexate

BackgroundClazakizumab (CLZ) is a potent, neutralizing anti-interleukin (IL)-6 monoclonal antibody that is being studied in RA. CLZ in combination with MTX (+ MTX) or as monotherapy demonstrated efficacy in controlling...

THU0485 The SPP1 Rs9138 Variant Contributes to the Severity of Radiologic Damage in Acpa-Negative Rheumatoid Arthritis: Results from the ESPOIR and Leiden EAC Cohorts

BackgroundGenetic variants are estimated to contribute most to the total variance in rheumatoid arthritis (RA) joint destruction, with clinical and serologic risk factors explaining only about one-third of the total...

FRI0226 93% of Early RA Patients Are Positive for 14-3-3Eta Markers and 14-3-3Eta Auto-Antibodies Inform A Favourable Prognosis, Irrespective of RF or ACPA Status

BackgroundParticular emphasis has been placed on early identification of RA patients and joint damage risk stratification to improve patient outcomes. The 14-3-3η (eta) protein has been described as a mechanistic...

AB0147 Role of Sclerostin in Rheumatoid Arthritis: New Insights

BackgroundRheumatoid arthritis (RA) is an autoimmune-inflammatory disease that may lead to joint destruction and disability Several key molecules are involved in the regulation of osteoclast differentiation, which are induced upon...

AB0231 Elevation of Serum Matrix Metalloproteinase-3 in A Group of Rheumatoid Arthritis Algerian Patients

BackgroundMatrix metalloproteinase-3 (MMP-3) is a protease induced by inflammatory cytokines in rheumatoid synovium and degrades a number of extracellular matrix components of cartilage and bone. Its central role in rheumatoid...

FRI0285 Initial Adalimumab plus Methotrexate Treatment Prevents Joint Destruction Irrespective of Treatment Duration in Japanese Patients with Early Rheumatoid Arthritis: Post-Hoc Analysis of HOPEFUL 1 and 2 Studies

BackgroundInformation about the most effective use of adalimumab (ADA) to prevent joint destruction in Japanese patients with early rheumatoid arthritis (RA) is unavailable.ObjectivesTo evaluate possible time to initiate ADA and...

SAT0260 Biomarkers Associated with Rheumatoid Arthritis Disease Activity Including Joint Damage Correlate with Changes in Clinical Response in Subjects Treated with Mavrilimumab at Doses above 10 Mg

BackgroundMavrilimumab is a human monoclonal antibody targeting the alpha subunit of GM-CSF receptor and was recently evaluated in RA subjects in a phase 2a study (EARTH). Results reported from the...

FRI0042 Validation of A Multi-Biomarker Disease Activity Score in Rheumatoid Arthritis in Relation to Imaging Inflammation and Damage

BackgroundA multi-biomarker disease activity (MBDA) score has been validated as a measure of disease activity in rheumatoid arthritis (RA).ObjectivesThis study aimed to further validate the MBDA score in relation to...

THU0131 Long Term Results of Inhibition of Radiographic Joint Damage Progression in Small and Medium and Large Joints in Patients with Rheumatoid Arthritis Treated with Tofacitinib Monotherapy

BackgroundTofacitinib is a novel oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). There was a study concerned with the efficacy for inhibiting the progression of radiographic...

AB0274 The Influence of Continuous Remission Rate on Functional Disability and Radiographic Progression for Rheumatoid Arthritis in A Japanese Observational Cohort

BackgroundOne goal of clinical remission in rheumatoid arthritis (RA) is to halt joint damage. The continuous clinical remission in established RA may result in improved function and reduced radiographic progression.ObjectivesThe...

AB1000 Assessing the Impact of Subcutaneous Abatacept in Inhibiting Structural Damage in Rheumatoid Arthritis by Low Field Magnetic Resonance Imaging and X-Ray

BackgroundRheumatoid arthritis (RA) treatment has shifted from reducing symptoms to earlier inhibition of disease progression, thus preventing irreversible structural damage and disability. Detection of synovitis (SYN), osteitis (OST), and erosions...