Rheumatoid Arthritis: Damjanov N

Damjanov N, Vojinović J. · No affiliation provided · Srp Arh Celok Lek. · Pubmed #19459571 No free full text.

Abstract: Rheumatoid arthritis (RA) and juvenile idiopathic/rheumatoid arthritis (JIA) are chronic, inflammatory, systemic, autoimmune diseases characterized by chronic arthritis leading to progressive joint erosions. The individual functional and social impact of rheumatoid arthritis is of great importance. Disability and joint damage occur rapidly and early in the course of the disease. The remarkably improved outcomes have been achieved initiating biologic therapy with close monitoring of disease progression. Biologic agents are drugs, usually proteins, which can influence chronic immune dysregulation resulting in chronic arthritis. According to the mechanism of action these drugs include: 1) anti-TNF drugs (etanercept, infiximab, adalimumab); 2) IL-1 blocking drugs (anakinra); 3) IL-6 blocking drugs (tocilizumab); 4) agents blocking selective co-stimulation modulation (abatacept); 5) CD 20 blocking drugs (rituximab). Biologics targeting TNF-alpha with methotrexate have revolutionized the treatment of RA, producing significant improvement in clinical, radiographic, and functional outcomes not seen previously. The new concept of rheumatoid arthritis treatment defines early diagnosis, early aggressive therapy with optimal doses of disease modifying antirheumatic drugs (DMARDs) and, if no improvement has been achieved during six months, early introduction of biologic drugs. The three-year experience of biologic therapy in Serbia has shown a positive effect on disease outcome.

Mandić D, Curcić R, Radosavljević G, Damjanov N, Stefanović D, Mitić I, Dimić A. · No affiliation provided · Srp Arh Celok Lek. · Pubmed #19459572 No free full text.

Abstract: Patients with an autoimmune disease, such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn's disease, ulcerative colitis, uveitis or psoriasis, and treated with the anti-tumour necrosis factor (TNF) alpha inhibitors are at high risk of developing various infections including tuberculosis (TB). Serious infections are the result of the patients' immunocompromised status that is caused by the primary disease itself, as well as by previous immunosuppressive therapy. In order to decrease the risk of developing TB, prior to the introduction of the anti-TNF alpha therapy, all patients should undergo screening for TB. Experiences from the countries that have already implemented recommendations for TB screening show a significant decrease in TB occurrence in the anti-TNF alpha treated patients. The PPD skin test result is considered positive if in duration is of size > or =5 mm. The BCG vaccine applied at birth has no effect on interpretation of PPD test results in adults. The diagnosis of active TB is contraindicated for the introduction of the anti-TNF alpha therapy; first, such patients should receive the TB treatment; and 6 months after the completion of the TB treatment, the introduction of the anti-TNF alpha therapy may be considered. The patients with the diagnosis of the latent TB infection (LTBI) should not immediately start with the anti-TNF alpha therapy, but they should first receive the TB chemoprophylaxis; not earlier than a month upon the introduction of the TB chemoprophylaxis, the anti-TNF alpha therapy may be introduced. The first TB follow-up screening during the anti-TNF alpha therapy is recommended 6 months after the anti-TNF alpha therapy has been introduced and the next one should be scheduled after 12 months.

Damjanov N, Kauffman RS, Spencer-Green GT. · Belgrade University School of Medicine, Belgrade, Serbia. · Arthritis Rheum. · Pubmed #19404957 No free full text.

Abstract: OBJECTIVE: To assess the efficacy and safety of VX-702, a p38 MAPK inhibitor, in patients with active, moderate-to-severe rheumatoid arthritis (RA). METHODS: Two 12-week, double-blind, placebo-controlled studies of VX-702 were conducted in patients with active, moderate-to-severe RA. In the VeRA study, 313 patients received placebo or 2 daily doses of VX-702. In Study 304, 117 patients received placebo, daily VX-702, or twice weekly VX-702 in addition to concomitant methotrexate (MTX). Study end points included the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (an ACR20 response), ACR50 and ACR70 responses, changes in the serum levels of biomarkers of inflammation, and safety assessments. RESULTS: The numerically superior ACR20 response rates among patients receiving VX-702 compared with those receiving placebo in both studies did not reach pairwise statistical significance at the highest doses in either study. At week 12 in the VeRA study, ACR20 response rates were 40%, 36%, and 28% among patients receiving 10 mg of VX-702, 5 mg of VX-702, and placebo, respectively. In Study 304, the response rates were 40%, 44%, and 22% for patients receiving 10 mg VX-702 daily plus MTX, 10 mg VX-702 twice weekly plus MTX, and placebo, respectively. Reductions in the levels of C-reactive protein, soluble tumor necrosis factor receptor p55, and serum amyloid A were observed as early as week 1 in both studies, but these levels rapidly returned to baseline values by week 4. The overall frequency of adverse events was similar between the VX-702 and placebo groups. In the VeRA study, serious infections were more frequent in the VX-702 groups compared with the placebo group (2.4% versus 0%) but not in Study 304 (2.6% versus 4.9%). CONCLUSION: The modest clinical efficacy plus the transient suppression of biomarkers of inflammation observed in this study suggest that p38 MAPK inhibition may not provide meaningful, sustained suppression of the chronic inflammation seen in RA.

Cohen SB, Cheng TT, Chindalore V, Damjanov N, Burgos-Vargas R, Delora P, Zimany K, Travers H, Caulfield JP. · Metroplex Clinical Research, Dallas, Texas 75235, USA. · Arthritis Rheum. · Pubmed #19180516 No free full text.

Abstract: OBJECTIVE: To determine the efficacy and safety of pamapimod (a selective inhibitor of the alpha-isoform of p38 MAP kinase) as monotherapy in comparison with methotrexate (MTX) treatment in adult patients with active rheumatoid arthritis (RA). METHODS: Patients were randomly assigned to 1 of 4 treatment groups and received 12 weeks of double-blind treatment. One group received MTX (7.5 mg/week with planned escalation to 20 mg/week), and 3 groups received pamapimod (50, 150, or 300 mg) once daily. The primary efficacy end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at 12 weeks. Secondary end points included ACR50 and ACR70 responses, change from baseline in the Disease Activity Score in 28 joints (DAS28), categorical analyses of DAS28/European League Against Rheumatism response, and change from baseline in each parameter of the ACR core set of measures. Safety monitoring included recording of adverse events (AEs), laboratory testing, immunology assessments, administration of electrocardiograms, and assessment of vital signs. RESULTS: Patients assigned to receive MTX and pamapimod had similar demographics and baseline characteristics. At week 12, fewer patients taking pamapimod had an ACR20 response (23%, 18%, and 31% in the 50-, 150-, and 300-mg groups, respectively) compared with patients taking MTX (45%). Secondary efficacy end points showed a similar pattern. AEs were typically characterized as mild and included infections, skin disorders, and dizziness. Pamapimod was generally well tolerated, but the 300-mg dose appeared to be more toxic than either the 2 lower doses or MTX. CONCLUSION: The present results showed that pamapimod was not as effective as MTX in the treatment of active RA.

Pavlov-Dolijanović S, Damjanov N, Ostojić P, Susić G, Stojanović R, Gacić D, Grdinić A. · Institute of Rheumatology-Belgrade, Resavska, Belgrade, Serbia and Montenegro. · Pediatr Dermatol. · Pubmed #17014637 No free full text.

Abstract: To assess the prognostic value of capillaroscopy findings for the development of connective tissue disease in children and adolescents with Raynaud phenomenon, we followed up a group of 250 (mean age 15 years) for 1 to 6 years after the first capillaroscopy was performed. Every 6 months they were screened for signs and symptoms of connective tissue disease. Analysis was performed on capillary changes registered 6 months before the development of connective tissue disease. Capillary changes were classified into three types: normal, nonspecific, and sclerodermatous. At the end of the follow-up period, 191 (76%) subjects had primary Raynaud phenomenon, 27 (10.8%) were diagnosed as having undifferentiated connective tissue disease, and 32 (12.8%) fulfilled the criteria for a diagnosis of a specific connective tissue disease. Systemic lupus erythematosus was found in nine (3.6%) patients, rheumatoid arthritis in 10 (4%) patients (six of them with juvenile onset rheumatoid arthritis), and scleroderma spectrum disorders in 13 (5.2%). The mean time for the evolution of Raynaud phenomenon into undifferentiated connective tissue disease or a form of the disease was 2 years. Most of the subjects with primary Raynaud phenomenon (173/191, 91%), undifferentiated connective tissue disease (22/27, 81%), juvenile onset rheumatoid arthritis/rheumatoid arthritis (7/10, 70%), and systemic lupus erythematosus (6/9, 67%) had normal capillary findings. Nonspecific capillary changes occurred in 3 of 10 (30%) patients with rheumatoid arthritis, 2 of 9 (22%) with systemic lupus erythematosus, 4 of 27 (15%) with undifferentiated connective tissue disease, and 18 of 191 (9%) with primary Raynaud phenomenon. Of all the subjects, only 10 (4%) showed sclerodermatous disease type capillary changes 6 months before the expression of a particular disease: eight (62%) of these developed scleroderma spectrum disorders, one expressed systemic lupus erythematosus, and one had undifferentiated connective tissue disease. We concluded that there were no specific capillary changes predictive for future development of systemic lupus erythematosus, juvenile onset rheumatoid arthritis/rheumatoid arthritis, and undifferentiated connective tissue disease in children and adolescents with Raynaud phenomenon. Most of our study subjects with Raynaud phenomenon who developed these diseases had normal capillary findings or nonspecific changes. Children and adolescents who developed scleroderma spectrum disorders showed a sclerodermatous type of capillary changes 6 months before the expression of the disease, indicating that this type of capillary changes in children and adolescents with Raynaud phenomenon highly correlated with further development of scleroderma spectrum disorders.