The impact of metabolic syndrome on rheumatoid arthritis in a cohort of Egyptian patients

Aim of the work

To assess the impact of metabolic syndrome (MetS) on the pattern and clinical presentation of rheumatoid arthritis (RA), and its relation to disease activity and functional status of the patients.

Assessment of health-related quality of life,anxiety and depression in patients with early rheumatoid arthritis

Aim of the workTo assess the effect of clinical manifestations, disease activity and medications on health-related quality of life (HRQoL) among patients with early rheumatoid arthritis (RA).Patients and methodsTwenty-six early RA patients (mean age 43.31 ± 10.51 years, disease duration: 16.5 ± 5.2 months) diagnosed according to the 2010 RA classification criteria were recruited from the outpatient clinic of the Rheumatology and Rehabilitation Department, Sohag University, and 22 age and sex matched healthy persons participated in a case control study. Demographic data were taken from all participants in the study. The 36-item short-form health survey (SF-36) and Hamilton Anxiety Rating Scale (HAM-A) were assessed as measures of HRQoL and psychiatric comorbidity for both patients and controls. Disease activity in RA was assessed using the disease activity score (DAS28). Scoring algorithms were applied to produce the physical and mental component scores (PCS and MCS).ResultsThere was statistically significant difference in the total SF36 score, anxiety and depression scores of HAM-A scale between patients and controls. The PCS showed the highest significant difference (p < 0.0001), followed by SF36 (p = 0.01) and MCS (p = 0.024). There were no significant differences according to the age, gender, occupation or level of education of the patients. Anxiety and depression scores significantly correlated with the bodily pain and DAS28 scores and inversely with the PCS and MCS. The DAS28 strongly negatively correlated with the PCS and MCS.ConclusionRheumatoid arthritis has a major impact on many areas of an individual’s life and tends to have a profound impact on the health-related quality of life.     

Development and validation of handy rheumatoid activity score with 38 joints (HRAS38) in rheumatoid arthritis patients receiving infliximab

The parameters involved in the Disease Activity Score of 28 joints (DAS28) are not mutually independent, and the evaluation excludes ankle and foot joints. We developed a new quantitative and comprehensive assessment of the activity of rheumatoid arthritis (RA), called the handy rheumatoid activity score, with 38 joints (HRAS38), to overcome these disadvantages of DAS28. Forty-six RA patients who recently completed a 1-year infliximab therapy were evaluated for DAS28 (C-reactive protein; CRP) and HRAS38 at 0, 2, 6, 14, 22, 30, 38, 46, and 54 weeks. The 38-joint evaluation in HRAS38 includes 28 joints of DAS28 except for the shoulder joints, with the addition of ankle and metatarsophalangeal joints. The extent of joint swelling was rated on a scale of 0–3. The HRAS38 score is the cumulative sum of three parameters including: (1) a global assessment of disease activity [visual analog scale (VAS) 0–100 mm] by the patient, (2) swollen joint score based on a 38-joint assessment by a physician (0–114), and (3) serum concentration of CRP (mg/l). Scatter plots of HRAS38 and DAS28(CRP), and subsequent linear regression analysis demonstrated a statistically significant correlation between methodologies (r = 0.846, P < 0.0001). Infliximab treatment resulted in a statistically significant (P < 0.001) decrease in the mean HRAS38 score from 130.5 to 56.5 within 2 weeks of treatment and at 52 weeks of therapy scores were still reduced at 52.5. The mean DAS28(CRP) was also significantly (P < 0.001) reduced from a baseline value of 5.8 to 3.7 after 2 weeks treatment with a final value of 3.2 after 52 weeks of therapy. Infliximab reduced the progression of joint destruction by 85%, for terms before infliximab as determined by radiographic analyses. The degree of progression appeared to be associated with the mean HRAS38, although this observation was not shown to be statistically significant by regression analysis (r = 0.307). The HRAS38 score comprises minimal and independently acquired parameters and is an effective and comprehensive measure of disease activity in RA patients.     

Development and validation of handy rheumatoid activity score with 38 joints (HRAS38) in rheumatoid arthritis patients receiving infliximab

Abstract

The parameters involved in the Disease Activity Score of 28 joints (DAS28) are not mutually independent, and the evaluation excludes ankle and foot joints. We developed a new quantitative and comprehensive assessment of the activity of rheumatoid arthritis (RA), called the handy rheumatoid activity score, with 38 joints (HRAS38), to overcome these disadvantages of DAS28. Forty-six RA patients who recently completed a 1-year infliximab therapy were evaluated for DAS28 (C-reactive protein; CRP) and HRAS38 at 0, 2, 6, 14, 22, 30, 38, 46, and 54 weeks. The 38-joint evaluation in HRAS38 includes 28 joints of DAS28 except for the shoulder joints, with the addition of ankle and metatarsophalangeal joints. The extent of joint swelling was rated on a scale of 0–3. The HRAS38 score is the cumulative sum of three parameters including: (1) a global assessment of disease activity [visual analog scale (VAS) 0–100?mm] by the patient, (2) swollen joint score based on a 38-joint assessment by a physician (0–114), and (3) serum concentration of CRP (mg/l). Scatter plots of HRAS38 and DAS28(CRP), and subsequent linear regression analysis demonstrated a statistically significant correlation between methodologies (r = 0.846, P < 0.0001). Infliximab treatment resulted in a statistically significant (P < 0.001) decrease in the mean HRAS38 score from 130.5 to 56.5 within 2 weeks of treatment and at 52 weeks of therapy scores were still reduced at 52.5. The mean DAS28(CRP) was also significantly (P < 0.001) reduced from a baseline value of 5.8 to 3.7 after 2 weeks treatment with a final value of 3.2 after 52 weeks of therapy. Infliximab reduced the progression of joint destruction by 85%, for terms before infliximab as determined by radiographic analyses. The degree of progression appeared to be associated with the mean HRAS38, although this observation was not shown to be statistically significant by regression analysis (r = 0.307). The HRAS38 score comprises minimal and independently acquired parameters and is an effective and comprehensive measure of disease activity in RA patients.     

Improvement of the HAQ score by infliximab treatment in patients with RA: its association with disease activity and joint destruction

Abstract

We conducted a two-year prospective study to clarify the efficacy of infliximab at improving the health assessment questionnaire (HAQ) score and associated factors in 67 patients with advanced rheumatoid arthritis (RA). All patients were scheduled to receive infliximab at a dose of 3 mg/kg at weeks 0, 2, 6 and every eight weeks thereafter through to week 102, and were fully examined at the time of each infusion. Parameters of disease activity such as the serum level of C-reactive protein (CRP), the serum level of matrix metalloproteinase-3 (MMP-3) and the 28-joint disease activity score (DAS28) were obtained, and the functional capabilities of the patients were assessed using the HAQ score. The serum CRP, the MMP-3, the DAS28(CRP) level, and the mean HAQ score decreased rapidly at two weeks after the start of infliximab treatment (CRP from 3.7 to 0.9 mg/dl, MMP-3 from 362.3 to 192.8 ng/ml, DAS28(CRP) from 5.6 to 3.7, and HAQ score from 1.5 to 0.9). Compared with the baseline values, the mean progression of the modified van der Heijde (vdH)–Sharp score after one year was 4.4 ± 5.8 (median: 3.0), and that after two years was 3.1 ± 6.9 (median: 1.0). A 93% reduction in the rate of joint destruction, as measured using the vdH–Sharp score, was estimated after infliximab therapy. Patients with less joint damage (shorter disease duration or lower vdH–Sharp score) regained more of their daily activities. The present study demonstrated the importance of activity control before the progression of irreversible factors, such as joint destruction, for maintaining the functional capacities of RA patients.     

Changes in serum interleukin-6 levels as possible predictor of efficacy of tocilizumab treatment in rheumatoid arthritis

Objectives: We aimed to evaluate the association between the change in serum IL-6 during the clinical course of tocilizumab (TCZ) therapy and rheumatoid arthritis (RA) disease activity or occurrence of adverse events.

Methods: General laboratory data including serum IL-6 levels and physical findings were obtained every 4 weeks, and, in addition, at the time when any adverse events occurred.

Results: The proportion achieving Clinical Disease Activity Index (CDAI) remission at 52 weeks was significantly lower in 20 patients with serum IL-6?≥?30?pg/ml at 12 weeks than 24 patients with serum IL-6?Conclusion: Serum IL-6 levels from 12 to 24 weeks after TCZ initiation better reflect the efficacy of TCZ at 52 weeks.     

Improvement of the HAQ score by infliximab treatment in patients with RA: its association with disease activity and joint destruction

We conducted a two-year prospective study to clarify the efficacy of infliximab at improving the health assessment questionnaire (HAQ) score and associated factors in 67 patients with advanced rheumatoid arthritis (RA). All patients were scheduled to receive infliximab at a dose of 3 mg/kg at weeks 0, 2, 6 and every eight weeks thereafter through to week 102, and were fully examined at the time of each infusion. Parameters of disease activity such as the serum level of C-reactive protein (CRP), the serum level of matrix metalloproteinase-3 (MMP-3) and the 28-joint disease activity score (DAS28) were obtained, and the functional capabilities of the patients were assessed using the HAQ score. The serum CRP, the MMP-3, the DAS28(CRP) level, and the mean HAQ score decreased rapidly at two weeks after the start of infliximab treatment (CRP from 3.7 to 0.9 mg/dl, MMP-3 from 362.3 to 192.8 ng/ml, DAS28(CRP) from 5.6 to 3.7, and HAQ score from 1.5 to 0.9). Compared with the baseline values, the mean progression of the modified van der Heijde (vdH)–Sharp score after one year was 4.4 ± 5.8 (median: 3.0), and that after two years was 3.1 ± 6.9 (median: 1.0). A 93% reduction in the rate of joint destruction, as measured using the vdH–Sharp score, was estimated after infliximab therapy. Patients with less joint damage (shorter disease duration or lower vdH–Sharp score) regained more of their daily activities. The present study demonstrated the importance of activity control before the progression of irreversible factors, such as joint destruction, for maintaining the functional capacities of RA patients.     

Differences between the Health Assessment Questionnaire Disability Index (HAQ-DI) and the modified HAQ (mHAQ) score before and after infliximab treatment in patients with rheumatoid arthritis

Abstract

We conducted a 1-year prospective study to clarify differences between the Health Assessment Questionnaire disability index (HAQ-DI) and the modified HAQ (mHAQ) score among rheumatoid arthritis (RA) patients treated with infliximab. A total of 87 patients were scheduled to receive infliximab infusion at a dose of 3 mg/kg at weeks 0, 2, and 6, and every 8 weeks thereafter for 54 weeks; all patients received a full examination at each infusion appointment. The 28-joint disease activity score (DAS28) and functional capability of each patient was assessed at each visit, using the HAQ-DI and the mHAQ score. A strong correlation was observed between the HAQ-DI and the mHAQ score at baseline (r = 0.892). Over the course of the treatment, the mean mHAQ score changed similarly to the HAQ-DI, but the mean HAQ-DI was significantly higher than the mean mHAQ score at each time-point (for the HAQ-DI vs. mHAQ score, baseline: 1.5 ± 0.7 vs. 0.9 ± 0.6, p < 0.0001; 6 weeks: 1.1 ± 0.7 vs. 0.6 ± 0.5, p < 0.0001; 30 weeks: 1.0 ± 0.7 vs. 0.6 ± 0.5, p < 0.0001; 54 weeks: 0.9 ± 0.7 vs. 0.6 ± 0.6, p = 0.0006). In the categories of “eating”, “reaching”, and “other activities”, the scores for several items excluded from the mHAQ score were significantly higher than those included in the mHAQ score over the year-long study period. We identified items contributing to significant differences between the HAQ-DI and the mHAQ score among RA patients treated with infliximab.     

The impact of fibromyalgia on disease assessment in rheumatoid arthritis patients

Aim of workTo explore the influence of the presence of concomitant fibromyalgia (FM) on the evaluation of disease activity score assessing 28 joints (DAS28), clinical disease activity index (CDAI) and modified health assessment questionnaire (MHAQ) in Egyptian patients with rheumatoid arthritis (RA).Patients and methodsThis study included 50 female RA patients; out of which 25 had concomitant FM (RAF group), the other 25 RA patients who served as controls did not have concomitant FM (RA group). All patients were subjected to an assessment of disease activity using the DAS 28 and the CDAI and assessment of functional outcome using MHAQ score.ResultsThe mean DAS 28 was significantly higher in RAF than RA patients (5.6 ± 1.1 versus 4.5 ± 1.3, P = 0.009). Also, the mean CDAI score was significantly higher in the RAF group (mean 23.3 ± 12.1 versus 13.7 ± 11.0, P = 0.002). The difference was attributed to significantly higher subjective items such as Tender joint count (TJC) and patient’s global assessment of general health (VAS-GH) in the RAF group. Mean MHAQ score was also higher in the RAF group (0.7 ± 0.6 versus 0.31 ± 0.4, P = 0.006).ConclusionFM is related to worse scores on the DAS28, CDAI and MHAQ in patients with RA. The presence of FM may have major implications in the interpretation of the DAS28 and CDAI scores because it is related to higher scores independently of objective evidence of RA activity.     

Factors associated with functional disability in patients with rheumatoid arthritis

To determine factors associated with functional disability in patients with rheumatoid arthritis (RA). A total of 100 RA patients were reviewed retrospectively. Multiple regression analysis was used to investigate associations between the dependent variable (health assessment questionnaire) and independent variables (age, disease duration, hand grip strength values, VAS and DAS-28 scores). Main factors associated with functional disability were disease activity score as reflected in a high score on the DAS-28 (r = 0.68, p < 0.001) and disease duration (r = 0.23, p < 0.05). Increased age, decreased grip strength and high pain level were associated with lower functional ability, but none of these was a predictor of disability in the regression model. The results indicate that age, disease duration, disease activity, pain intensity and hand grip strength are related to physical disability in patients with RA. However, only disease activity has an impact on physical function. Thus, treatment of RA patients should focus on early inhibition of disease activity in order to achieve a good functional outcome.     

Efficacy of total joint arthroplasty in patients with established rheumatoid arthritis: improved longitudinal effects on disease activity but not on health-related quality of life

Abstract

Though excellent clinical results have been reported for total joint arthroplasty (TJA) in rheumatoid arthritis (RA) patients, the longitudinal effects of TJA on pain, physical function, and health-related quality of life in RA patients remain unknown. This study aimed to assess changes in disease activity and health-related quality of life after TJA in patients with established RA. We analyzed the effect of total knee arthroplasty (TKA) and total hip arthroplasty (THA) on RA disease activity in an observational cohort of RA patients. Of the registered RA patients, 333 TKA and 77 THA patients were followed for 5 years after surgery. RA disease activity and health-related quality of life were measured using the Disease Activity Score 28 (DAS28) and a Japanese version of the Stanford health assessment questionnaire (J-HAQ). The mean DAS28 in TKA patients decreased from 4.66 (preoperatively) to 4.02 (3 years postoperatively) and to 3.94 (5 years postoperatively); the mean DAS28 in THA patients decreased from 4.41 (preoperatively) to 3.99 (3 years postoperatively) and to 3.92 (5 years postoperatively). The mean J-HAQ for TKA remained essentially unchanged, ranging from 1.48 (preoperatively) to 1.45 (3 years postoperatively) and to 1.47 (5 years postoperatively); the mean J-HAQ for THA also remained unchanged, ranging from 1.74 (preoperatively) to 1.74 (3 years postoperatively) and to 1.73 (5 years postoperatively). Of the total J-HAQ score, the lower limb score improved while the upper limb score worsened. Although TKA and THA improve clinical outcomes in damaged knees and hips and have a positive secondary systemic effect on RA disease activity, they have not had a continuously good effect on the measures of health-related quality of life. We conclude that tight control of RA disease activity is indicated for those patients with TKA and/or THA.     

Diagnostic value and clinical significance of anti-carbamylated protein (anti-CarP) antibodies in Egyptian patients with rheumatoid arthritis

Aim of the workThe study was performed to assess the diagnostic potential of anti-carbamylated proteins (anti-CarP) antibodies in Egyptian patients with RA and their relation to clinical manifestations, laboratory findings and radiological damage.Patients and methodsThe study involved 90 RA patients and 90 matched healthy controls. Disease activity score (DAS28) and health assessment questionnaire (HAQ) were assessed. Plain x-ray hands and feet were performed and assessed by modified Larsen’s score. Laboratory investigations including acute phase reactants, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) and anti-CarP antibodies were estimated.ResultsThe patients mean age was 42.6 ± 10.4 years (20–60 years), disease duration was 4.3 ± 3.3 years and were 82 females (91.1%) and 8 males (8.9%). The mean DAS28 was 4.9 ± 1.2, HAQ was 1.6 ± 0.7 and Larsen score 33.8 ± 12.2. 29/90 (32.2%) patients were positive for anti-CarP antibodies and were significantly associated with extra-articular manifestations and deformity (p < 0.001), but not with acute phase reactants. Anti-CarP antibodies significantly associated with modified Larsen’s (p < 0.001), but not DAS28 (p = 0.13). The sensitivity and specificity were 32.2% and 96.7% for anti-CarP antibodies, 61.1% and 97.8% for anti-CCP antibodies, 66.7% and 91.1% for RF respectively. 25.7% of anti-CCP negative patients showed anti-CarP positivity, and radiological damage was significantly associated with anti-CarP in them.ConclusionThe sensitivity of anti-CarP antibodies was low in comparison to both RF and anti-CCP; however, they showed high specificity and were detected in anti-CCP negative patients, so they could be useful to test beside anti-CCP and RF. Anti-CarP antibodies may reflect disease radiological damage.     

Twenty-four-week follow-up examination of a leukocytapheresis therapy in rheumatoid arthritis

Several clinical trials have demonstrated that leukocytapheresis (LCAP) is a safe and effective therapy for patients with refractory rheumatoid arthritis (RA). However, most of those reports were limited to short-term clinical observation. We have treated 11 RA patients with LCAP and observed them for 24 weeks after the final administration. The 11 cases included 3 diabetes patients, 2 patients with interstitial pneumonia, 1 patient with diffuse panbronchiolitis, and 1 patient with old pulmonary tuberculosis. Alternative therapies for all of these patients were considered difficult. Once-a-week LCAP administration was added for 5 weeks to the previous therapeutic regime in all patients, and the treatment efficacy was prospectively qualified. At 4 weeks after the final LCAP therapy, 8 of the 11 patients (73%) had achieved an American College of Rheumatology (ACR) 20% response, and 3 of the 11 (27%) had achieved both ACR 50% and ACR 70% responses. Although the efficacy decreased after the observation periods, an ACR 20% response was maintained in 5 patients (45%) at 24 weeks. Although only a limited number of patients were examined in this study, the results suggested that LCAP therapy will be beneficial to RA patients, including patients who cannot be treated with tumor necrosis factor inhibitors or conventional disease-modifying antirheumatic drugs.     

Twenty-four-week follow-up examination of a leukocytapheresis therapy in rheumatoid arthritis

Abstract

Several clinical trials have demonstrated that leukocytapheresis (LCAP) is a safe and effective therapy for patients with refractory rheumatoid arthritis (RA). However, most of those reports were limited to short-term clinical observation. We have treated 11 RA patients with LCAP and observed them for 24 weeks after the final administration. The 11 cases included 3 diabetes patients, 2 patients with interstitial pneumonia, 1 patient with diffuse panbronchiolitis, and 1 patient with old pulmonary tuberculosis. Alternative therapies for all of these patients were considered difficult. Once-a-week LCAP administration was added for 5 weeks to the previous therapeutic regime in all patients, and the treatment efficacy was prospectively qualified. At 4 weeks after the final LCAP therapy, 8 of the 11 patients (73%) had achieved an American College of Rheumatology (ACR) 20% response, and 3 of the 11 (27%) had achieved both ACR 50% and ACR 70% responses. Although the efficacy decreased after the observation periods, an ACR 20% response was maintained in 5 patients (45%) at 24 weeks. Although only a limited number of patients were examined in this study, the results suggested that LCAP therapy will be beneficial to RA patients, including patients who cannot be treated with tumor necrosis factor inhibitors or conventional disease-modifying antirheumatic drugs.     

CD14++CD16+ monocyte subset expansion in rheumatoid arthritis patients: Relation to disease activity and interleukin-17

Aim of the workMonocytes are divided into three major subsets based on the expression of the cluster of differentiation CD14 and CD16. The aim of this work was to determine which of the CD16⁺ monocyte subpopulations is expanded in rheumatoid arthritis (RA) and its association with disease activity and interleukin-17 (IL17) levels.Patients and methodsFifty-three RA patients and 20 controls were enrolled in this study. Flow cytometry was performed to detect monocyte subsets and IL17 was measured by ELISA. Disease activity score (DAS28) was assessed.ResultsCD14⁺⁺CD16⁺ monocyte percentage was significantly higher in long standing RA patients compared with early patients and controls (p < 0.01, p < 0.001 respectively). It was significantly higher in patients with RA disease activity and remission compared with the controls (p < 0.001, p < 0.01 respectively). It was not significantly associated with resistance to disease modifying antirheumatic drugs (DMARDs), C-reactive protein, rheumatoid factor and anti-CCP positivity (p > 0.05). It significantly correlated with IL17 (p < 0.002). CD14⁺CD16⁺ monocyte percentage was not significantly correlated with any of the above parameters. IL17 level was significantly higher in patients with early and long standing RA compared to controls (p < 0.01, p < 0.001 respectively). IL17 was higher in RA patients with active disease compared to those in remission and controls (p < 0.01, p < 0.001 respectively). It was higher in RA patients resistant to DMARDs than in responding patients (p < 0.017).ConclusionCD14⁺⁺CD16⁺ monocyte subpopulation was expanded in long standing RA and was correlated with IL17 levels indicating its potential pathogenic importance in RA and may represent an attractive target for future therapeutic interventions.     

Achieving simplified disease activity index remission in patients with active rheumatoid arthritis is associated with subsequent good functional and structural outcomes in a real-world clinical setting under a treat-to-target strategy

Objective: To verify predictive validity of simplified disease activity index (SDAI) remission for subsequent functional and structural outcomes in real-world clinical settings under a treat-to-target strategy (T2T).

Methods: In this multicenter, prospective cohort study, T2T was implemented in rheumatoid arthritis (RA) patients with moderate-to-high disease activity. SDAI or clinical disease activity index (CDAI) was assessed every 12 weeks, and treatment was adjusted to achieve clinical remission or low disease activity (LDA). Multivariate logistic regression models were used to examine the associations of SDAI remission (≤3.3) at week 24 with the health assessment questionnaire-disability index (HAQ-DI)?≤?0.5 or with the delta van der Heijde-modified total Sharp score (ΔvdH-mTSS)?Results: Of 318 patients enrolled, 271 completed the follow-up for 72 weeks and were subjects of the analyses. Factors [odds ratio (95% confidence interval)] significantly associated with the HAQ-DI ≤0.5 were SDAI remission at week 24 [2.99 (1.42–6.28), p?=?0.004], baseline HAQ-DI [0.28 (0.18–0.45), p?=?1.3?×?10^?7], and baseline vdH-mTSS [0.986 (0.976–0.996), p?=?0.009]. A factor associated with ΔvdH-mTSS?p?=?0.002].

Conclusion: Predictive validity of SDAI remission for good outcomes was verified in a T2T-implementing cohort in the current clinical settings.