Reem Hamdy A . Mohammed

Background: Inhibitors of tumor necrosis factor alpha (TNF-α) are current mainstay of therapies for rheumatoid arthritis (RA). The decision when to withdraw TNF-α inhibitors after achieving remission and the incidence of relapse rates with elective discontinuation are both important questions that demand intense survey in these patients. In this meta-analysis we aimed to estimate the magnitude of relapse rate after elective TNF-α inhibitor discontinuation in RA patients with remission.

Methods: Systematic searches of PubMed/MEDLINE, Cochrane Library databases, grey literature (unpublished and ongoing trials) from the WHO International Clinical Trials Registry Platform and the US National Institutes of Health were performed for studies reporting the outcomes of elective discontinuation of TNF-α inhibitor in RA patients after remission. Random-effects models for meta-analyses were conducted on extracted data.

Results: Out of 390 references screened, 16 RCTs were included. Meta-analysis of 1264 patient data revealed a relapse rate of 0.47 (95% CI 0.41-0.54). Sensitivity analysis showed that none of the studies had higher influence on the results.

Conclusions: Almost half of all the RA patients in remission relapse after elective TNF-α inhibitor discontinuation. This information might be useful when considering this management option with individual patients.

PURPOSE: This study aimed at investigating the prevalence of crystal deposits with knee osteoarthritis (OA) by ultrasonography and measure the inflammatory burden associated with crystal deposits in OA using WOMAC score.

METHODS: Adult patients with primary knee OA diagnosed according to the American College of Rheumatology criteria were included. Participants were subjected to history taking, clinical examination, knee US, and plain radiography. The EULAR and the OMERACT ultrasonography definitions and scanning protocols were used.

RESULTS: Fifty-three patients (44 females, 9 males) were enrolled. Mean values were 53.5 years ± 8.3 SD for age and 42.5 months ± 49.5 SD for disease duration. Crystals were detected by US in 73/106 knees (68.9%). Plain radiography revealed chondrocalcinosis in three patients. Mean values for WOMAC pain, stiffness, and disability scores were 14.38 ± 3.99, 4.93 ± 2.06, and 49.61 ± 13.06, respectively, with insignificant differences relative to presence of crystals (P > 0.05). Regression analysis revealed a 4.1-fold increase in the incidence of sonographic crystals with bursitis (OR = 4.13, CI = 1.5-11.2, p = 0.01) and a 3.2-fold increase in the incidence of sonographic crystals with synovial effusion (OR = 3.16, CI = 1.34-7.44, p = 0.01).

CONCLUSION: Subclinical crystals were detected in a considerable number of patients with primary knee OA. The incidence of crystal deposits was significantly higher in patients with bursitis and knee effusion.

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AIM: The goal of the present study was to prospectively assess the long-term clinical outcome of biologic modifying drug therapy in a population of Saudi rheumatoid arthritis (RA) patients.

PATIENTS AND METHODS: This is the first prospective, long-term report on the efficacy and safety of biologic therapy in Saudi RA patients. It is a single center, observational study with a follow-up period of 3 years. Enrolled were 120 biologic naïve patients (94 women, 78.3 %; mean age 48.4 ± 17.9 years, mean disease duration 7.3 ± 3.9 years) with the diagnosis of RA (ACR/EULAR, 2010 criteria) who were inadequate responders to methotrexate and synthetic DMARDs.

RESULTS: After 3 years, the mean Disease Activity Index-28 (DAS-28), Health Assessment Questionnaire (HAQ), Pain Score, ESR, and CRP values improved significantly. Of the 99 patients completing the 3-year follow-up, 35.3 % of patients achieved DAS-28 remission and 53.5 % achieved low disease activity, and 11.1 % of patients had moderate to high activity scores. At the 3-year follow-up, 80 % of patients had no evidence of significant radiographic progression (achieved < 0.5 of the mean total Sharp score). Infections were reported in 11.7 % and significantly correlated with conjugate use of oral prednisolone at doses above 5 mg/day, with chest infections being the most common type of infection (6.7 %).

CONCLUSION: The results of this study can be understood as real-life clinical experience displaying the incremental benefit of biologic therapy in refractory disease when it is added to other optimal strategies. The study showed satisfying clinical and functional benefit with considerable safety.

STUDY OBJECTIVE: The goal of the present study was to investigate patient outcome when using the TNF receptor fusion protein etanercept in addition to conventional immunosuppressive drugs in ameliorating disease intensity and reducing relapses in refractory Behçet's disease (BD).

PATIENTS AND METHODS: A single center, prospective study was conducted over 1 year. A total of 15 patients with the established diagnosis of BS were enrolled (mean age: 36.5 ± 6.75 years, mean disease duration: 3.86 ± 1.30 years). Clinical features were classified as refractory if the patients failed to achieve the desired response within 6 months of immunosuppressive and oral glucocorticoid therapy or flare of lesions developed while on the maximum tolerable doses of these drugs. The study included 2 patients who were on previous infliximab therapy for refractory disease. Inflammatory biomarkers (ESR and CRP) were investigated.

RESULTS: Baseline clinical features in the study prior to inclusion showed recurrent oro-genital ulcers were observed in 100 % of patients, the pathergy test was positive in 17.6 %, ocular involvement was observed in 86.7 %, and acne lesions were recorded in 73.3 %. The following values were also recorded: mean ESR 22 ± 16.97 mm/h, mean CRP level 6.87 ± 4.44 mg/l, mean visual analog score 5.46 ± 1.55, and mean patient global score 5.13 ± 1.30. At the beginning of the study, all patients were on oral prednisolone (mean dose: 20.16 ± 11.81 mg/day), azathioprine (mean dose: 126.66 ± 25.81 mg/day), and oral colchicine (mean dose: 1.08 ± 0.10 mg/day), then etanercept was added at a regular weekly dose of 50 mg subcutaneously for 1 year. By 8 weeks, 100 % of the patients achieve the primary endpoint, which included clinical resolution of refractory mucocutaneous, joint, and active ocular lesions with normalization of the acute phase symptoms.

CONCLUSION: Patients with refractory BD who received a 12-month treatment with etanercept in addition to conventional immunosuppressive therapy achieved a good therapeutic response with successful reduction of oral prednisolone to a mean dose of 6.66 ± 2.24 mg/day. No serious infections or drug-related adverse events reported.

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To investigate the sensitivity and specificity of sero-positivity to antibodies against modified citrullinated vimentin antibodies (anti-MCV) in comparison with anti-CCP2- in rheumatoid arthritis (RA) among Egyptians, considering the possible correlation to demographic and disease related features in the study group.

Patients and methods: This study included forty patients with Rheumatoid arthritis (RA) and thirty matching healthy controls. Patients’ assessment measures involved the disease activity score (DAS-28), visual analogue scale (VAS) and health assessment questionnaire (HAQ). Thirty healthy subjects matched for age and sex served as a control group. Blood samples were obtained from patients and controls for erythrocyte sedimentation rate (ESR), C reactive protein (CRP), rheumatoid factor (RF). Anti-CCP2 and anti-MCV were determined using ELISA technique.

Results: Estimated serum levels of anti-CCP2 and anti-MCV were significantly higher in patients compared to controls (p<0.001). Serum levels of anti-MCV didn’t show any significant variations with age, disease duration, duration of morning stiffness, number of swollen and tender joints, HAQ or ESR in patients with RA, yet serum levels of anti-MCV correlated significantly with DAS28, VAS and CRP (p<0.05). Anti-CCP2 correlated significantly with DAS28, VAS and CRP and ANA (p<0.05). Serum levels of anti-MCV and anti-CCP2 showed a consistently significant correlation with each other (r=0.483; p<0.001). Statistical analysis showed that anti-MCV had diagnostic specificity, sensitivity of 93.3%, 75.5%, respectively, while anti-CCP2 specificity, sensitivity of 98.1%, 85%, respectively.

Conclusion: Serum anti-MCV as well as the anti-CCP-2 assay perform comparably well in the diagnosis of RA. In the high-specificity range, however, the anti-CCP2 assay appears to be superior to the anti-MCV test.

d: Behcet's disease (BD) is a chronic relapsing multisystem inflammatory where Tumor necrosis factor alpha is believed to play a pivotal role.[1-3]
Objectives: Investigate the benefit of one year treatment with etanercept, a TNF- receptor fusion protein in ameliorating disease intensity and reducing relapses in patient refractory to conventional immunosuppressive drugs.
Methods: Single center prospective study over a period of one year. Patients with the established diagnosis of BD based on the criteria of the international study group [4] who were classified as having refractory ocular or muco-cutaneous disease while on conventional immuno-suppressive therapy were enrolled. Laboratory workup including markers of acute inflammatory disease including erythrocyte sedimentation rate ESR and C- reactive protein CRP.
Results: The study included 15 patients with the established diagnosis of BS, they included 14 males and 1 female, their ages ranged between 24-45 (mean 36.5+-6.75years), disease duration 2-7 years (mean 3.86+-1.30years). Baseline clinical assessment showed recurrent oro-genital ulcers in 100% of patients, pathergy test was positive in 17.6%, recurrent uveitis (> 1attack/year) and refractory retinitis in 86.7% of cases, acne lesions in 73.3%, deep venous thrombosis in 33.3%. Laboratory investigations showed ESR a mean of (22+-16.97) a range from 4-65mm/hr, mean CRP 6.87+-4.44 mg/l, medication history showed 100% of the patients were on oral prednisolone 10-60mg/day (mean 20.16+-11.81mg/day), azathioprine 100-150mg/day (mean126.66+-25.81mg/day) and oral colchicine 1-1.2mg/day (1.08+-0.10), 20% were on cyclophosphamide pulse therapy (750 mg), 17.6% were on oral cyclosporine (5-10mg/kg/day) in addition to topical steroids, oral anticoagulants in 33,3%. Etanercept was initiated at regular weekly dose of 50mg subcutaneously over a period of one year. Assessment at the end of study period showed 86.6% (13 patients) to have <1 attack of recurrent oro-genital ulcers, acne lesions, arthralgias/arthritis, with 100% of the patients having 0 recurrences of uveitis and remission of retinal vasculitic lesions. Laboratory markers of inflammation revealed a mean ESR of 6.2+-3.82 mm/hr(2-14mm/hr), a mean CRP 2.90+-2.11mg/l (0.2-5.6mg/l). The dose of oral prednisolone was successfully reduced with etanercept reaching a mean of 6.66+-2.24 mg/day (5-10mg/day) with a statistically significant difference between the pre-post TNF-I therapy inflammatory markers including mean ESR (t= 4.13, P= 0.001), mean CRP (t= 3.9, P= 0.008), and mean prednisolone dose (t= 4.39, P= 0.001).
Conclusions: Patient with refractory BD received a 12-month treatment with etanercept achieved a good therapeutic response. No serious infections or drug related adverse events reported.