The role of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) in the response to treatment for rheumatoid arthritis (RA) is not fully understood. Studies investigating changes in the levels of RF in response to synthetic and biological DMARDs have not been able to confirm a definitive relationship between decreased RF subtypes and clinical response, while studies investigating changes in anti-CCP levels have yielded conflicting results. In addition, to our knowledge the correlation between autoantibodies and tocilizumab treatment has been poorly investigated.
Objectives
This study investigates the relationship between the presence and levels of RF and anti-CCP and clinical response to tocilizumab in patients with RA.
Methods
This was an observational longitudinal study in 27 patients with active, long-standing RA despite previous treatment with >2 DMARDs and/or steroids. Patients were treated with tocilizumab 8 mg/kg every 4 weeks. All patients were assessed using approved clinical scales (VES, PCR, HAQ, DAS28-VES, DAS28-PCR, CDAI, and SDAI). IgM-, IgA- and IgG-RFs and anti-CCP antibodies were assessed using ELISA at baseline, 3 months (T1), 6 months (T2), and 12 months (T3).
Results
All patients showed significant and sustained clinical response to tocilizmuab treatment. All clinical scales with the exception of HAQ significantly decreased. There was a significant correlation (p=0.03) between anti-CCP and SDAI changes from baseline at T1 and T2. Likewise there were no significant correlations between antibody count at T0 and changes in the DAS-28 VES at T1 and at T2. No significant relationship between clinical scales and antibody levels RF-IgG, IgA, IgM and anti-CCP levels were observed.
Conclusions
Tocilizumab is effective in treating the clinical symptoms of RA, and the efficacy of this molecule was not correlated with either RF or anti-CCP levels. There is now a growing body of evidence suggesting that markers associated with clinical response may not be the same biomarkers that predict risk of further joint damage
References
MIKULS TR, O'DELL JR, STONER JA, ET AL: Association of rheumatoid arthritis treatment response and disease duration with declines in serum levels of IgM rheumatoid factor and anti-cyclic citrullinated peptide antibody. Arthritis Rheum 2004; 50: 3776–82. KARSDAL MA, WOODWORTH T, HENRIKSEN K, ET AL: Biochemical markers of ongoing joint damage in rheumatoid arthritis--current and future applications, limitations and opportunities. Arthritis Res Ther 2011; 13: 215 TAKEUCHI T, TANAKA Y, AMANO K, ET AL: Clinical, radiographic and functional effectiveness of tocilizumab for rheumatoid arthritis patients-REACTION 52-week study. Rheumatology 2011; 50: 1908–15.
The objective of this study was to evaluate the rates of previously undiagnosed rheumatic diseases during the first trimester of pregnancy and their impact on the pregnancy outcome.Pregnant women in their first trimester were screened using a two-step approach using a self-administered 10-item questionnaire and subsequent testing for rheumatic autoantibodies (antinuclear antibody, anti-double-stranded DNA, anti-extractable nuclear antigen, anticardiolipin antibodies, anti-β2-glycoprotein I antibodies and lupus anticoagulant) and evaluation by a rheumatologist. Overall, the complications of pregnancy evaluated included fetal loss, pre-eclampsia, gestational diabetes, fetal growth restriction, delivery at less than 34 weeks, neonatal resuscitation and admission to the neonatal intensive care unit.Out of the 2458 women screened, the authors identified 62 (2.5%) women with previously undiagnosed undifferentiated connective tissue disease (UCTD) and 24 (0.98%) women with previously undiagnosed definite systemic rheumatic disease. The prevalences were seven (0.28%) for systemic lupus erythematosus and Sjogren's syndrome, six (0.24%) for rheumatoid arthritis, three (0.12%) for antiphospholipid syndrome and one (0.04%) for systemic sclerosis. In multiple exact logistic regression, after adjustment for potential confounders, the OR of overall complications of pregnancy were 2.81 (95% CI 1.29 to 6.18) in women with UCTD and 4.57 (95% CI 1.57 to 13.57) in those with definite diseases, respectively, compared with asymptomatic controls.In our population approximately 2.5% and 1% of first trimester pregnant women had a previously undiagnosed UCTD and definite systemic rheumatic disease, respectively. These conditions were associated with significant negative effects on the outcome of pregnancy.
To delineate, within the framework of current clinical practice and criteria, the sustainability of first-line immuno-suppressive treatment discontinuation in rheumatoid arthritis (RA) and the impact of residual disease in remission on long-term drug-free (DF) outcomes. RA patients, referring to the Pavia early arthritis clinic (EAC) between 2009 and 2021 and achieving remission after Disease Activity Score-driven methotrexate (MTX) monotherapy, were recruited. Eligible patients underwent DF follow-up at 3-month intervals over 5 years after MTX discontinuation. Pre-selected clinical, serological and ultrasound (US) exposure variables at MTX withdrawal were analysed using multivariable Cox regression to predict time-to-flare. Of 761 EAC patients with RA, 132 started DF follow-up (person-months: 3678). 62 experienced a flare after a median (range) of 9 (3-60) months, resulting in a progressive decline in flare-free survival throughout the observation period. Whole-cohort multivariate Cox regression identified anti-citrullinated protein antibody (ACPA) positivity (HR: 4.20, 95% CI 2.37 to 7.44) and hands' joints with grey scale (US-GS) alterations (GS>1; HR: 2.18, 95% CI 1.20 to 3.93) as independent predictors. ACPA-positive patients in Simplified Disease Activity Index (SDAI) remission displayed a flare-free survival estimate at 5 years of 6.4% (95% CI 1.2 to 35.7) versus 78.2% (95% CI 67.4 to 90.8) for ACPA-negative patients in SDAI remission without residual US-GS alteration in hands' joints (n=59); the latter group showing no evidence of radiographic progression and functional deterioration. Long-term DF remission is attainable in a niche subset of ACPA-negative RA. Examining clinical and subclinical residual synovial abnormalities during remission allows for effective preemptive identification of this subset in real life.
The aim of the present study was to investigate the effect of long-term infliximab treatment on various autoantibodies in patients with rheumatoid arthritis. Serum samples from 30 consecutive patients, who were prospectively followed during infliximab and methotrexate therapy for refractory rheumatoid arthritis, were tested at baseline and after 30, 54 and 78 weeks. At these points, median values of the Disease Activity Score were 6.38 (interquartile range 5.30-6.75), 3.69 (2.67-4.62), 2.9 (2.39-4.65) and 3.71 (2.62-5.06), respectively. Various autoantibodies were assessed by standard indirect immunofluorescence and/or ELISA. Initially, 50% of patients were positive for antinuclear antibodies, and this figure increased to 80% after 78 weeks (P = 0.029). A less marked, similar increase was found for IgG and IgM anticardiolipin antibody titre, whereas the frequency of anti-double-stranded DNA antibodies (by ELISA) exhibited a transient rise (up to 16.7%) at 54 weeks and dropped to 0% at 78 weeks. Antibodies to proteinase-3 and myeloperoxidase were not detected. The proportion of patients who were positive for rheumatoid factor (RF) was similar at baseline and at 78 weeks (87% and 80%, respectively). However, the median RF titre exhibited a progressive reduction from 128 IU/ml (interquartile range 47-290 IU/ml) to 53 IU/ml (18-106 IU/ml). Anti-cyclic citrullinated peptide (CCP) antibodies were found in 83% of patients before therapy; anti-CCP antibody titre significantly decreased at 30 weeks but returned to baseline thereafter. In conclusion, the presence of anti-double-stranded DNA antibodies is a transient phenomenon, despite a stable increase in antinuclear and anticardiolipin antibodies. Also, the evolution of RF titres and that of anti-CCP antibody titres differed during long-term infliximab therapy.
To evaluate if the timing of appearance with respect to disease onset may influence the arthritis presentation pattern in antisynthetase syndrome (ASSD).The patients were selected from a retrospective large international cohort of ASSD patients regularly followed-up in centres referring to AENEAS collaborative group. Patients were eligible if they had an antisynthetase antibody testing positive in at least two determinations along with arthritis occurring either at ASSD onset (Group 1) or during the course of the disease (Group 2).445 (70%; 334 females, 110 males, 1 transsexual) out of the 636 ASSD we collected had arthritis, in the majority of cases (367, 83%) from disease onset (Group 1). Patients belonging to Group 1 with respect to Group 2 had an arthritis more commonly polyarticular and symmetrical (p=0.015), IgM-Rheumatoid factor positive (p=0.035), erosions at hands and feet plain x-rays (p=0.036) and more commonly satisfying the 1987 revised classification criteria for rheumatoid arthritis (RA) (p=0.004). Features such as Raynaud's phenomenon, mechanic's hands and fever (e.g. accompanying findings) were more frequently reported in Group 2 (p=0.005).In ASSD, the timing of appearance with respect to disease onset influences arthritis characteristics. In particular, RA features are more common when arthritis occurs from ASSD onset, suggesting an overlap between RA and ASSD in these patients. When arthritis appears during the follow-up, it is very close to a connective tissue disease-related arthritis. Also, the different prevalence of accompanying features between these two groups is in line with this possibility.
Abstract : This article will focus on the relationship between serum levels of anti‐citrullinated peptide antibodies (anti‐CCP) or rheumatoid factor (RF) and clinical response to TNF‐α blockers in order to evaluate whether these antibodies may have a role as serological markers of response to therapy in rheumatoid arthritis (RA). The changes induced in anti‐CCP levels after TNF blocking therapy still remain a controversial issue even though a marked reduction following conventional DMARDs has been reported in early disease. On the other hand, a drop in RF levels during treatment has been reported by many authors. Decreased IgM RF levels seem to parallel clinical response suggesting that this antibody can also be regarded as a marker of response to treatment. Pre‐treatment RF positivity or negativity does not influence response to TNF‐α blocking therapy while high pre‐treatment levels of IgA RF seem to be associated with a poor response rate.