Short-term outcome after anti-tumor necrosis factor-alpha therapy in rheumatoid arthritis: do we need to revise our assessment criteria?

OBJECTIVE: To evaluate the Disease Activity Score (DAS) using various aggregated dimensions to quantify treatment outcome in patients with rheumatoid arthritis (RA), in order to determine the best instrument to be used as an endpoint that indicates good response in terms of EULAR response criteria and DAS28 remission criteria, and which satisfies the demands of clinical rheumatology. METHODS: Using raw data for each patient subjected to anti-tumor necrosis factor-a therapy (81 patients), before and 6 months after treatment, DAS28 was calculated 4 times using the standard equation, as follows: (1) DAS 1 (the standard DAS28): tender joint count (TJC), swollen joint count (SJC), patient global assessment (PGA), erythrocyte sedimentation rate (ESR); (2) DAS 2: TJC, SJC, PGA, C-reactive protein (CRP); (3) DAS 3: TJC, SJC, physician global assessment (PhGA), ESR; and (4) DAS 4: TJC, SJC, PhGA, CRP. Disease activity was identified if DAS score exceeded 5.1. A clinically significant response was recorded if there had been improvement of > 1.2 of the DAS score. RESULTS: DAS 2, DAS3, and DAS4 were superior to the current DAS score used for assessment of RA activity (effect size differences were -0.35, -0.13, and -0.48, respectively). Assessment of disease activity using TJC, SJC, PhGA, and CRP was the best tool to assess response to therapy. ESR was marginally superior to CRP in its sensitivity to monitor disease activity changes (effect sizes 1.08 and 1.03, respectively). CONCLUSION: These results suggest that self-report indices on their own, such as PGA and pain score, are inadequate indicators of disease activity. The DAS might profitably be amended by one or 2 continuous measures for better quantification of the degree of improvement of patients on a given therapeutic modality. Using PhGA and CRP instead of PGA and ESR, respectively, in the DAS equation discriminated better between different patients' responses than the traditional DAS score.     

ESR or CRP,which inflammatory measure can accurately replace clinical measures in rheumatoid arthritis?

BackgroundESR and CRP are two commonly used laboratory inflammatory parameters. The controversy remains which of the two is a better measure to use and which parameter closely reflects the clinical measures of inflammation as well the disease process in Rheumatoid arthritis.MethodsWe used mountain plot analysis to find out the congruency of ESR and CRP individually with clinical measures namely Tender joint count (TJC), Swollen joint count (SJC) and Visual analogue scale for Pain (VAS). 303 RA patients who are in our regular follow-up were included in the study. There TJC, SJC and VAS pain and ESR and CRP were retrieved.Results242 were female and 61 were male patients. The mean age was 46.8 years (17–79 years), mean duration of illness was 70.81 (3–307) months. All of them were on conventional DMARD with majority on combination of methotrexate, Hydroxychloroquine and/or leflunomide. Both ESR and CRP correlated with all three measures such as TJC, SJC and VAS. The correlation was stronger with ESR than CRP. When the effectiveness of ESR vs CRP was compared for their overlapping on the clinical parameters TJC, SJC and VAS by using mountain plot method, CRP performed better than ESR and coincided with all three clinical parameters of the disease RA.ConclusionOur study emphasizes the fact that CRP is a better measure of inflammation than ESR and represents the information on the inflammatory component provided by both TJC and SJC, as appreciated by the close overlap. The CRP can replace the clinical measures (joint counts and Pain scale) more effectively than ESR, provided other causes for elevation of CRP are excluded.     

Disease activity score 28 as an instrument to measure disease activity in patients with early rheumatoid arthritis

OBJECTIVE: To examine the influence of components of the Disease Activity Score 28 (DAS28) [tender joint count (TJC), swollen joint count (SJC), patient's general health (GH), and erythrocyte sedimentation rate (ESR)] on the total DAS28 score, and overlapping of the 4 individual components in rheumatoid arthritis (RA) patients with low, moderate, or high disease activity. METHODS: The effect of each component was studied in the FIN-RACo trial patients at 6 months and in a "theoretical model," where each component of the DAS28 ranged as follows: TJC and SJC from 0 to 28, GH from 0 to 100, and ESR from 1 to 100, while the other 3 components were 0 (ESR1). Overlapping of the components was studied in the FIN-RACo trial patients at 6 months with low (DAS28 < or = 3.2), moderate (DAS28 > 3.2 and < or = 5.1), and high (DAS28 > 5.1) disease activity. The higher limit for overlapping was defined as the highest SJC in the low disease activity group, and the lower limit as the lowest SJC in the high disease activity group; the percentage of patients who fall between these limits represent overlapping in SJC. Overlapping was calculated similarly concerning TJC, ESR, and GH. RESULTS: ESR had the greatest effect on DAS28, followed by TJC, GH, and SJC, while in the "theoretical model" TJC had the greatest effect on the DAS28, followed by ESR, SJC, and GH. At 6 months, overlapping was present in 54%, 45%, 49%, and 31% of patients in SJC, TJC, GH, and ESR, respectively. CONCLUSION: In real-life patients, ESR had the greatest effect of the 4 components of DAS28 on the total DAS28 score. The values of the individual components of DAS28 overlap considerably among the 3 disease activity groups.     

Antibodies against cyclic citrullinated peptide don��t decrease after 6?months of infliximab treatment in refractory rheumatoid arthritis

Anti-citrullinated peptide antibodies (ACPA) and the rheumatoid factor (RF) are well-established serological markers for rheumatoid arthritis (RA). ACPA are very useful in the diagnosis of RA, especially at the early stages of the disease when ACPA have a greater diagnostic value than RF. The aim of the study was to assess the influence of infliximab treatment on RF IgM and ACPA serum levels and RA activity during 6 months of treatment. Thirty-two patients with refractory RA were treated with infliximab during a 6-month period. At baseline, 3 and 6 months of treatment the patients were examined for the number swollen and tender joints out of 28 (SJC, TJC) and the visual analogue scale of arthritis activity according to the patient (VAS). Serum samples were tested for erythrocyte sedimentation rate (ESR), C-reactive protein level (CRP), ACPA and RF IgM. The disease activity score (DAS-28) parameter was also calculated at the same time. During the course of our study, we observed statistically significant improvement in ESR, CRP, TJC, SJC, VAS DAS-28, and RF IgM after 3 and 6 months of infliximab treatment when compared to the baseline, whereas the ACPA level remained unchanged after 3 and 6 months of treatment (P = 0.96 and P = 0.85). The changes in the ACPA level are not a factor for evaluation of successful infliximab treatment but the changes in RF IgM are. According to different behavior of these antibodies during infliximab treatment, we suggest that the roles of ACPA and RF in the pathogenesis of RA are different.     

The relationship between disease activity and depression in Egyptian patients with rheumatoid arthritis

Aim of the workTo estimate the prevalence of depression and its relationship with disease activity parameters in Egyptian patients with RA.Patients and methodsA cross sectional study was conducted on 170 patients with RA. The following values were assessed for each patient: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), swollen and tender joint counts (SJC and TJC), disease activity score 28 (DAS28), health assessment questionnaire score (HAQ), visual analogue scale (VAS) of pain and hospital anxiety and depression scale-depression subscale (HADS-D).ResultsThe prevalence of depression was 15.29% (26 RA patients). In the depressed RA patients, positive significant correlations were found between HADS-D score and age, disease duration, HAQ score, VAS, DAS28 score and CRP. However, no significant correlation was found between HADS-D score and ESR, number of swollen and tender joints. No significant difference (P > 0.05) was found between depressed male and female patients with RA.ConclusionPatients with RA and co-morbid depression have worse health outcomes. RA cases should be monitored for accompanying depression during follow-up. The identification and treatment of depression in RA paramount to the overall management of RA.     

Serum matrix metalloproteinase 3 levels during treatment with sulfasalazine or combination of methotrexate and sulfasalazine in patients with early rheumatoid arthritis

OBJECTIVE: To determine the effects of treatment with sulfasalazine (SSZ) or the combination of methotrexate (MTX) and SSZ on serum matrix metalloproteinase 3 (MMP-3) levels in patients with early rheumatoid arthritis (RA). METHODS: Eighty-two patients with early RA (symptoms < 1 year and DMARD-naive at presentation) were selected who had been treated with SSZ (2000 mg/day) or with the combination of MTX (7.5-15 mg/week) and SSZ. Serum MMP-3 levels, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), swollen joint count (SJC), tender joint count (TJC), Ritchie articular index (RAI), and the Disease Activity Score (DAS) were determined at 4 week intervals during a followup of 28 weeks for each treatment group. Response was based on clinical grounds and CRP at 12, 20, and 28 weeks. RESULTS: SSZ responders (n = 52) had lower baseline values of serum MMP-3, CRP, and ESR, compared to partial/nonresponders (n = 30), but did not differ in joint scores and DAS. In the SSZ responder group all variables decreased. In the SSZ partial/nonresponders, CRP, ESR, and SJC decreased in contrast to serum MMP-3, TJC. RAI, and DAS-3. After addition of MTX all variables decreased in 24 of the 30 patients who had shown a partial or no response taking SSZ. In the SSZ responders there was a delayed decrease in serum MMP-3 compared to CRP. CONCLUSION: Serum MMP-3 levels decrease in patients with early RA who respond to SSZ or to the combination of MTX and SSZ. In patients who respond to SSZ the changes in serum MMP-3 levels indicate a delayed response compared to CRP.     

The association of anti-CCP antibodies with disease activity in rheumatoid arthritis

Antibodies to citrullinated proteins have been described in patients with rheumatoid arthritis (RA) and these appear to be the most specific markers of the disease. Our objective was to determine the frequency of antibodies to cyclic citrullinated peptides (CCPs) in patients with RA and the association of anti-CCP antibodies with disease activity, radiological erosions and HLA DR genotype. Forty patients with RA and 38 patients with fibromyalgia were included in this study. Serum samples were collected from both patient groups with RA and fibromyalgia. Anti-CCP was measured by the corresponding enzyme-linked immunosorbent assay. Additionally, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), disease activity score (DAS), visual analog scala (VAS), HLA genotype and radiographic information were determined in patients with RA. The rate of sensitivity and specificity of anti-CCP reactivity for the diagnosis RA were measured (sensitivity 50%, specificity 100%). There is no significant difference between anti-CCP (+) and anti-CCP (-) RA patients for DAS28, VAS, ESR, CRP, disease duration, HLA genotype, and radiological assessment of hand. However, there was a significant difference between anti-CCP (+) and anti-CCP (-) RA patients for RF and the radiological assessment of left and right wrists (respectively, P < 0.05, P = 0.04, P = 0.01). There was no significant correlation between anti-CCP antibody and ESR, CRP, VAS, DAS 28 or radiological assessment. A small but significant correlation was found between RF and anti-CCP antibody (P = 0.02, r = 0.35).     

Remission occurs still only in minority of rheumatoid arthritis while a tight control is achievable in a routine clinical practice – A cross section study

The current recommended target is to achieve remission, if not at least low disease activity (LDA) in management of rheumatoid arthritis (RA). We analysed the incidence of patients achieving LDA or in remission in a real time clinical situation in a tertiary referral rheumatology centre, at a given point of time.Materials and methodsWe reviewed 480 patients who fulfilled classification criteria for RA and who were assessed for 28 Tender Joint Count (TJC), Swollen Joint Count (SJC), ESR and CRP. Their DAS28 (3) CRP and DAS28 (3) ESR score were calculated and were classified into LDA, remission, low, moderate and high disease activity based on the DAS28 (3) score.Results5.9% and 21.9% were in remission and 12% and 10% were in LDA based on DAS28 (3) ESR and DAS28 (3) CRP respectively. There was no significant influence of duration of illness, treatment and age in attaining both LDA and remission in our population.Conclusion5.9% and 21.9% of RA were in remission based on DAS28 (3) ESR and DAS28 (3) CRP respectively and 12% and 10% of RA patients were in LDA based on DAS28 (3) ESR and DAS28 (3) CRP respectively at the point of our study. DAS (3) CRP overestimate remission compared to DAS28 (3) ESR.     

血清抗突变型瓜氨酸波形蛋白抗体在类风湿关节炎诊断中的价值

目的探讨抗突变型瓜氨酸波形蛋白(MCV)抗体在类风湿关节炎(RA)诊断中的价值。方法采用ELISA法测定68例RA患者(RA组)、62例关节疼痛及自身免疫性疾病患者(疾病对照组)、129例健康体检者(正常对照组)的抗MCV抗体、抗环瓜氨酸肽(CCP)抗体水平,计算抗MCV抗体与抗CCP抗体诊断RA的敏感性与特异性;速率散射比浊法检测CRP水平,记录压痛关节数(TJC)、肿胀关节数(SJC),并计算DAS28积分值。对抗MCV抗体与抗CCP抗体及DAS28积分(包括CRP、TJC、SJC三个变量)进行Spearman秩相关性分析。结果 RA组抗MCV抗体、抗CCP抗体、DAS28积分值显著高于疾病对照组及正常对照组;抗MCV抗体与抗CCP抗体诊断RA的敏感性分别为88.2%(60/68)、75.0%(51/68),P=0.026;特异性分别为97.3%(186/191)、95.8%(183/191),P=0.548。抗MCV与抗CCP抗体呈显著正相关(r=0.826,P<0.05);抗MCV与RA活动度指标DAS28积分及CRP、肿胀关节数间均有明显相关性。结论抗MCV抗体在RA诊断中较抗CCP抗体具有更高的敏感性和特异性,能为RA诊断提供良好的依据,且抗MCV抗体与RA病情活动度指标相关,高滴度的抗MCV可能在一定程度上提示RA的病情活动。     

Serum matrix metalloproteinase 3 levels in comparison to C-reactive protein in periods with and without progression of radiological damage in patients with early rheumatoid arthritis

OBJECTIVE: To evaluate serum matrix metalloproteinase 3 (MMP-3) levels in comparison to C-reactive protein (CRP) in periods with and without progression of radiological damage in patients with early rheumatoid arthritis (RA). METHODS: Thirty-two patients with RA and radiological progression (> or = 5 points according to the Sharp/van der Heijde method) during 6 months followed by a 6-month period without radiological progression (< or = 1 point) were selected from a prospective follow-up study of early RA patients. Serum MMP-3 levels, CRP, the erythrocyte sedimentation rate (ESR), disease activity index (DAS), swollen joint count (SJC), tender joint count (TJC), and Ritchie articular index (RAI) were measured monthly and results were transformed into mean values for the 6-month periods. RESULTS: During the period with radiological progression the mean serum MMP-3 correlated significantly with the mean CRP (r = 0.68, p < 0.001), ESR (r = 0.54, p = 0.001) and swollen joint count (r = 0.48, p = 0.006). In the period without radiological progression the mean serum MMP-3 only correlated with the mean CRP (r = 0.44, p = 0.012). Individual changes--expressed in percentages (%)--between the two periods showed a decrease in both the mean serum MMP-3 and CRP in 19 and an increase in 3 patients, in parallel with other markers of disease activity in these patients (69% of cases). The individual change (%) in mean serum MMP-3 or CRP did not correlate with the difference in radiological progression between the two periods. CONCLUSIONS: Serum MMP-3 and CRP are closely related and there seems to be no difference between serum MMP-3 and CRP with regard to the monitoring of the progression of radiological damage.     

Serum matrix metalloproteinase 3 in early rheumatoid arthritis is correlated with disease activity and radiological progression

OBJECTIVE: To analyze the clinical significance of serial measurements of serum matrix metalloproteinase 3 (MMP-3) levels in relation to markers of disease activity and radiological progression in early rheumatoid arthritis (RA). METHODS: In a 3 year prospective study of 33 patients with early RA (symptoms < 1 year at entry) monthly measurements of serum MMP-3 were transformed into time integrated values for 6 month periods for comparison with other markers of disease activity like swollen joint count (SJC), tender joint count (TJC), Ritchie articular index (RAI), the disease activity score (DAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and radiological progression, scored according to Sharp's method, in which erosions and joint space narrowing are scored separately and combined to a total Sharp score. RESULTS: Significant correlations were found between serum MMP-3 and SJC, ESR, and CRP during all periods and between 6 and 30 months with the DAS. There were no correlations between serum MMP-3 and TJC or the RAI. During the first 12 months serum MMP-3 was correlated only with the item joint space narrowing of the Sharp score. After 12 months of followup it was also correlated with the total Sharp score and after 18 months it was correlated with all 3 items of the Sharp score. There was a wide interindividual variation in the relation between serum MMP-3 and radiological progression but intraindividually this relation seemed to be rather constant. CONCLUSION: Time integrated values of serum MMP-3 are correlated with time integrated values of other markers of disease activity such as joint swelling, ESR, CRP, and the DAS. Of the radiological scores, as outcome measures, especially joint space narrowing correlated closely with cumulative serum MMP-3.     

Prevalence and predictive value of anti-cyclic citrullinated protein antibodies for future development of rheumatoid arthritis in early undifferentiated arthritis

The aim of this study is to evaluate the prevalence and predictive value of anti-cyclic citrullinated protein (CCP) antibodies as a diagnostic marker for future development of rheumatoid arthritis (RA) in a cohort of patients presenting with undifferentiated arthritis (UA). The study comprised 69 patients (22 males and 47 females) presenting with UA, and 66 healthy subjects as control group. For all patients the following parameters were assessed: swollen joint count (SJC), tender joint count (TJC), and duration of morning stiffness in minutes. Baseline laboratory investigations included erythrocyte sedimentation rate (ESR) first hour, C-reactive protein (CRP), complete blood count, complete liver and kidney function tests, urine analysis, anti-nuclear antibodies, rheumatoid factor (RF), and anti-CCP antibodies. Positive correlations were observed between anti-CCP versus SJC, TJC (p = 0.001), duration of morning stiffness (p = 0.04), ESR first hour, and bone erosive changes (p = 0.001). Anti-CCP showed sensitivity of 57%, specificity of 37.9%, positive predictive value of 65.1%, and negative predictive value of 39.3%. Sensitivity and positive predictive values of anti-CCP are close to those observed for RF. In patients presenting with UA, anti-CCP antibodies may allow prediction of RA, thereby allowing early individualized therapeutic decisions.     

The effectiveness of a traditional therapeutical approach in early psoriatic arthritis: results of a pilot randomised 6-month trial with methotrexate

Thirty-five patients with Early Psoriatic Arthritis (EPA) (17 female and 18 male; mean age 25.6 years) entered this randomised 6-month study. At the enrolment, all patients were on non-steroidal anti-inflammatory drug (NSAID) therapy on demand and were divided in two matched groups (A and B). Group A continued NSAID therapy at full dosage in the following 3 months and then added methotrexate (MTX) for another 3 months. Group B was under the combination of NSAID and MTX for the entire 6-month period. Clinical and laboratory assessment included the count of tender joints and/or entheses (TJC), the count of swollen joints and/or entheses (SJC), patient's global assessment (PGA), physician's global assessment (PhGA), patient's assessment of pain (VAS), erythrocyte sedimentation rate (ESR) and serum concentration of C-reactive protein (CRP). All variables were done at baseline (T0), at 3 (T3) and at 6 months (T6). In both group A and in group B, there was a significant improvement of all variables at T3 and T6. However, in comparison to the patients of group A, patients included in group B showed a more rapid and marked improvement of TJC and SJC, which was statistically significant at T3 (p < 0.05). In contrast, the improvement of PGA, PhGA, VAS, ESR and CRP was not significantly different between groups. The early use of MTX in EPA patients markedly improves TJC and SJC. In fact, at T3, other markers used to quantify EPA disease activity, in particular PGA, PhGA, VAS, ESR and CRP, did not show significant differences in EPA patients treated with either NSAIDs or MTX. This finding suggests an incomplete control under MTX of the pathogenetic process and stimulates further interest on early use of other therapeutical approaches capable of modifying the course of disease.     

Monotherapy with tocilizumab or TNF-alpha inhibitors in patients with rheumatoid arthritis: efficacy, treatment satisfaction, and persistence in routine clinical practice

This study aims to investigate the use of biological disease-modifying antirheumatic drugs (bDMARDs) as monotherapy in patients with rheumatoid arthritis (RA) in “real world” clinical settings and to compare tumor necrosis factor (TNF) inhibitors and tocilizumab monotherapy in terms of efficacy and patient and clinician satisfaction with treatment. This study made use of a retrospective, cohort-19 based study including included data from 254 patients (TNF inhibitors n?=?128; tocilizumab n?=?126) managed in 30 centers throughout Germany. Efficacy of monotherapy and patient and physician overall satisfaction with treatment were assessed at baseline, 3, and 6 months of monotherapy using a range of measures including Disease Activity Score 28 joint (DAS28), swollen joint count (SJC) and tender joint count (TJC), and visual analogue scales (VAS). Between 18 and 41 % of patients treated with bDMARDs received the agent as monotherapy. Intolerance to DMARDs, contraindications for combination therapy, and comorbidities were the most common reasons for introduction of bDMARD monotherapy. Mean DAS28 (erythrocyte sedimentation rate, ESR) was significantly lower at 3 and 6 months following tocilizumab vs. TNF inhibitors (p?≤?0.001). Joint counts improved from baseline to month 6 in both groups (SJC ?5.1 vs. ?3.7 and TJC ?5.6 vs. ?5.1, for tocilizumab and TNF inhibitors, respectively). Patient as well as physician satisfaction (VAS 100 mm scale) was significantly higher for tocilizumab vs. TNF inhibitors (75.3 vs. 66.8; p?=?0.001 and 74.9 vs. 67.1, p?=?0.003, respectively). Significantly more patients remained on tocilizumab monotherapy vs. TNF-inhibitor monotherapy (89.7 vs. 75.8 %; p?<?0.01). Monotherapy with bDMARDs is common in routine clinical practice. Tocilizumab monotherapy appeared to be superior over TNF-inhibitor monotherapy with respect to DAS28 and drug adherence.     

Presence of power Doppler synovitis in rheumatoid arthritis patients with synthetic and/or biological disease-modifying anti-rheumatic drug-induced clinical remission: experience from a Chinese cohort

The aim of this study was to evaluate the ultrasonographic synovitis in rheumatoid arthritis (RA) patients who reached clinical remission. Two hundred and two RA patients were enrolled into this study. One hundred and eleven RA patients achieved clinical remission with the treatment of synthetic and/or biologic disease-modifying anti-rheumatic drugs (DMARDs). Subclinical synovitis was assessed by power Doppler ultrasonography (PDUS). PD synovitis was semi-quantitatively recorded. Twenty-two joint regions were imaged: bilateral wrists, metacarpophalangeal (MCP) joints, and proximal interphalangeal (PIP) joints. PD remission was defined as a total PD score of 0. The subclinical synovitis in the RA patients who achieved clinical remission was evaluated. The correlations between PD total scores and clinical/laboratory parameters were analyzed. Among the 111 RA patients who achieved clinical remission, 110 (99.1 %), 67 (60.4 %), 55 (49.5 %), 50 (45.0 %), and 54 (48.6 %) patients, respectively, satisfied DAS28 (CRP), DAS28 (ESR), CDAI, SDAI, and 2010 ACR/EULAR remission criteria. However, only 54 (48.6 %) patients achieved PD remission. Subclinical synovitis was detectable in 57 (51.8 %), 30 (44.8 %), 22 (40.0 %), 19 (38.0 %), and 18 (33.3 %) patients accordingly. On the contrary, 11 (26.8 %) out of 41 patients who fulfilled all five clinical remission criteria had evidence of subclinical synovitis. In those 91 patients who did not achieved clinical remission, total PD score was correlated with swollen joint counts (SJC), tender joint counts (TJC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complex disease activity indexes (P?<?0.01), but not the titers of rheumatoid factor and anti-cyclic citrullinated peptide. Among those 57 patients with subclinical synovitis after reaching clinical remission, no correlation was found between PD total score and SJC, TJC, ESR, CRP, and complex disease activity indexes. Presence of subclinical synovitis is common in patients achieving clinical remission. The stricter clinical remission criteria may reflect less PD synovitis. In patients with active RA, PD total score of synovitis was positively correlated with disease activity.     

Calprotectin (a major leucocyte protein) is strongly and independently correlated with joint inflammation and damage in rheumatoid arthritis

OBJECTIVE: Calprotectin is a major leucocyte protein, shown to correlate well with laboratory and clinical assessments in several inflammatory rheumatic diseases, and large concentrations of calprotectin have been found in synovial fluid from patients with rheumatoid arthritis (RA). The objective of the present study was to examine correlations between calprotectin and joint damage. METHODS: 145 patients with RA were analysed cross sectionally with laboratory (calprotectin, C reactive protein (CRP), and erythrocyte sedimentation rate (ESR)), clinical (28 joint counts (tender, swollen), physician global VAS, DAS28 and RA Articular Damage score (RAAD)), and radiographic (plain hand radiographs; modified Sharp's method) measurements, on the same day. RESULTS: Calprotectin showed a highly significant correlation with measures of joint damage; modified Sharp score r = 0.43 (p<0.001) and RAAD r = 0.40 (p<0.001). The association with modified Sharp score and RAAD score was maintained after adjustment for CRP, ESR, rheumatoid factor, DAS28, sex, and age in a multiple regression analysis (p = 0.018 and p = 0.04, respectively), while neither CRP nor ESR showed any independent associations. Highly significant correlations (p<0.001) were also found between calprotectin and both laboratory and clinical markers of inflammation. CONCLUSION: Calprotectin was found to significantly and independently explain the variation in the radiological and clinical assessments of joint damage. Longitudinal studies are required to examine whether calprotectin may predict the progression of joint damage in RA.     

The effects of tobacco smoking and rheumatoid factor seropositivity on disease activity and joint damage in early rheumatoid arthritis

OBJECTIVE: To study the effect of tobacco smoking and rheumatoid factor (RF) isotypes on disease activity and joint damage in early rheumatoid arthritis (RA). METHODS: One hundred early RA patients were followed prospectively for 2 yr. They were evaluated at recruitment and at 6 and 24 months. Sociodemographic information included smoking history, and radiographs of hands and feet were obtained. RF was monitored by IgM- and IgA-specific RF enzyme-linked immunosorbent assay and by agglutination, and serial measurements were also obtained for C-reactive protein. The influence of tobacco smoking and RF positivity on disease outcome was evaluated using multivariate analysis. Covariates for the regression analysis included sex, age, coffee consumption and IgA-RF positivity. RESULTS: A gradient of increase in disease activity was observed from never smokers to former smokers to current smokers during the 2 yr of observation, defined by number of swollen joints (SJC), tender joints (TJC) and visual analogue scale for pain (P<0.001, P=0.02 and P=0.005, respectively), but smoking status did not influence radiological progression. Ever smokers were more often IgA RF positive (P<0.05). IgA RF-positive patients had more active disease (SJC P=0.002, TJC P=0.01) and showed more radiological progression (P<0.0001) compared with IgA RF-negative patients. Of the RF-positive patients 22% had elevated IgM RF without IgA RF and these patients showed similar disease activity and radiological joint progression to the RF-negative patients. None of these associations were explained by possible confounders. CONCLUSION: Tobacco smoking has an adverse effect on patients with early RA and this is possibly immunologically mediated. IgM RF does not predict poorer prognosis in RA unless it is associated with a concomitant elevation of IgA RF.     

Effect of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitor on Disease Activity in Patients With Rheumatoid Arthritis: A Meta-Analysis

HMG-CoA reductase inhibitors (also known as statins) are widely used as lipid-lowering agents in patients with rheumatoid arthritis (RA) to reduce their cardiovascular risk. However, whether they have an effect on RA disease activity is controversial.This study aimed to investigate the effect of statins on disease activity in RA patients.A systematic literature review was performed using the MEDLINE, EMBASE, Cochrane Library, ISI WEB of Knowledge, Scopus, and Clinical Trials Register databases.Only prospective randomized controlled trials or controlled clinical trials comparing the efficacy of statins with placebo on adult RA patients were included. The efficacy was measured according to the ACR criteria, EULAR criteria, DAS28, HAQ score, ESR, or CRP.The Jadad score was used for quality assessment. The inverse variance method was used to analyze continuous outcomes. A fixed-effects model was used when there was no significant heterogeneity; otherwise, a random-effects model was used. For stability of results, we performed leave-one-study-out sensitivity analysis by omitting individual studies one at a time from the meta-analysis. Publication bias was assessed using Egger test.A total 13 studies involving 737 patients were included in the meta-analysis; 11 studies were included in the meta-analysis based on DAS28, while the other 2 studies were only included in the meta-analysis based on ESR or CRP. The standardized mean difference (SMD) in DAS28 between the statin group and the placebo group was −0.55 (95% CI [−0.83, −0.26], P = 0.0002), with an I² value of 68%. Subgroup analysis showed that patients with more active disease tended to benefit more from statin therapy (SMD −0.73, P = 0.01) than patients with moderate or low disease activity (SMD −0.38, P = 0.03). Statin therapy also significantly reduced tender joint counts, swollen joint counts, ESR, and CRP compared with placebo, but the reduction in HAQ score and VAS was not significant (P > 0.05).This meta-analysis suggested that statin therapy might be effective in the reduction of RA disease activity measured by DAS28, TJC, SJC, as well as ESR and CRP.     

Relation of interleukin-6 in rheumatoid arthritis patients to systemic bone loss and structural bone damage

IL-6 plays a key role in local and systemic manifestation of RA. IL-6 is not only a pro-inflammatory cytokine, but also interacts in complex ways with the cells involved in bone remodeling. In RA, IL-6 may indirectly promote osteoclastogenesis by increasing the release of RANK-L by osteoblasts, and it diminishes the proliferation of osteoblasts at late differentiation stages. The aims of this work were to evaluate the level of serum IL-6 and to correlate it with the activity, severity, early development of osteoporosis, and early structural bone damage in RA patients. The following parameters were investigated in 40 RA patients and 20 healthy controls: IL-6 level, BMI, ESR, CRP, CBCs, serum ionized calcium, blood urea, serum creatinine, AST, ALT, anti-CCP, and RF. Bone mineral density was measured by dual-energy X-ray absorptiometry at lumbar spines and femoral neck. Drug history was taken stressing on steroid therapy. Data were processed and analyzed using computer-based program. IL-6 was significantly positively correlated with HAQ1, PTGA, grade of pain, ESR, platelet count, blood urea, AST level, and anti-CCP level; IL-6 showed an inverse significant correlation with T-score. IL-6 was positively correlated with TGC, DAS-28 score, and RF level. No correlation was found between T-score and morning stiffness duration, BMI, CRP, RBC, serum creatinine, and ALT. There was an inverse significant correlation between T-score and HAQ1, SJC, pain grade, DAS-28 score, PTGA, ESR, RF, anti-CCP, and IL-6. Patients with RA on steroid therapy had significantly higher TJC, SJC, and DAS-28 score, anti-CCP, and IL-6 than patients with RA not on steroid therapy. Patients with RA on steroid therapy had significantly lower T-score and lower serum ionized calcium than patients with RA not on steroid therapy. IL-6 has an important role in increasing osteoclastic activity and subsequent bone resorption in the patients with RA. Blocking IL-6 by using IL-6 inhibitors and anti-RANK-L therapy may be effective in inhibiting the inflammatory process and preventing the bone complications of RA disease.