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ID PMID Title PublicationDate abstract
19070549 Patient barriers to pain management may contribute to poor pain control in rheumatoid arth 2009 Mar We have examined the characteristics of the pain experience as well as barriers to optimal pain management in 60 patients with rheumatoid arthritis (RA) consecutively attending a specialist rheumatology practice. Pain was reported to be moderate to severe in 32 (53%) and mild to absent in 28 (47%). Sixty-five percent of all patients, including almost half of those with moderate to severe pain, reported satisfaction with current pain control. The average number of barriers to pain management for individual patients was 2.6 +/- 1.5, with 33 patients (55%) reporting 3 or more barriers. Specific barriers included concern about side effects of medications in 80%, dislike for "too many pills" in 63%, concern about drug interactions in 57%, fear of addiction in 35%, and fear of masking disease in 27% of the patients. More barriers were significantly associated with higher pain level (r = .33, P = .011) and pain intensity on a visual analogue scale (r = .29, P = .024). Other than the regular use of nonsteroidal anti-inflammatory drugs in 37% of the patients and acetaminophen in 37%, analgesics or other modalities to reduce pain were seldom used. PERSPECTIVE: Moderate to severe pain was present in over half of patients with RA with many reporting the presence of considerable barriers to pain control. These barriers likely contribute to sub optimal pain management. RA patients tolerate pain and use limited mechanisms to deal with the symptom of pain.
16819695 Skin protection underneath the pneumatic tourniquet during total knee arthroplasty: a rand 2006 Jun BACKGROUND: The use of a pneumatic tourniquet to obtain a bloodless field during a total knee arthroplasty (TKA) allows the surgeon to work with greater technical precision in a safe, clear environment. Despite the benefits of surgical tourniquets and many advances in tourniquet equipment, their use is not without risk and complications may still occur. The primary aim of this study was to determine whether there are any differences between an elastic stockinette, cast padding, and no protective material at all regarding skin injuries after a primary TKA in a bloodless field using a pneumatic tourniquet. METHODS: 92 patients were randomized to 1 of 3 groups. In the first group, the limb underneath the pneumatic tourniquet was protected by a two-layer elastic stockinette (E). In the second group, it was protected by cast padding (C), and no protective material (N) was used in the third group. The presence of major skin injuries (blisters) was recorded when the tourniquet was removed after surgery. RESULTS: The two groups with skin protection had fewer skin injuries (p = 0.007). The elastic stockinette was significantly better than having no protective material and there was a trend towards better results in the elastic stockinette group than in the cast padding group. INTERPRETATIONS: Our findings indicate that protective material underneath the tourniquet cuff reduces the risk of skin injuries, i.e. blisters. An elastic stockinette appears to be best.
17612407 Expression and function of junctional adhesion molecule-C in human and experimental arthri 2007 Junctional adhesion molecule-C (JAM-C) is an adhesion molecule involved in transendothelial migration of leukocytes. In this study, we examined JAM-C expression in the synovium and investigated the role of this molecule in two experimental mouse models of arthritis. JAM-C expression was investigated by reverse transcriptase-polymerase chain reaction and immunohistochemistry. The effects of a monoclonal anti-JAM-C antibody were assessed in antigen-induced arthritis (AIA) and K/BxN serum transfer-induced arthritis. JAM-C was expressed by synovial fibroblasts in the lining layer and associated with vessels in the sublining layer in human and mouse arthritic synovial tissue. In human tissue, JAM-C expression was increased in rheumatoid arthritis (RA) as compared to osteoarthritis synovial samples (12.7 +/- 1.3 arbitrary units in RA versus 3.3 +/- 1.1 in OA; p < 0.05). Treatment of mice with a monoclonal anti-JAM-C antibody decreased the severity of AIA. Neutrophil infiltration into inflamed joints was selectively reduced as compared to T-lymphocyte and macrophage infiltration (0.8 +/- 0.3 arbitrary units in anti-JAM-C-treated versus 2.3 +/- 0.6 in isotype-matched control antibody-treated mice; p < 0.05). Circulating levels of the acute-phase protein serum amyloid A as well as antigen-specific and concanavalin A-induced spleen T-cell responses were significantly decreased in anti-JAM-C antibody-treated mice. In the serum transfer-induced arthritis model, treatment with the anti-JAM-C antibody delayed the onset of arthritis. JAM-C is highly expressed by synovial fibroblasts in RA. Treatment of mice with an anti-JAM-C antibody significantly reduced the severity of AIA and delayed the onset of serum transfer-induced arthritis, suggesting a role for JAM-C in the pathogenesis of arthritis.
18270853 Comparison of three anti-CCP antibody tests and rheumatoid factor in RA and control patien 2008 Feb It was the aim of this study to compare the diagnostic properties of two second generation anti-CCP antibodies assays (Quanta Lite CCP, Inova and EliA CCP, Phadia) with an assay containing a new antigen mixture (Quanta Lite CCP 3, Inova) and RF IgM. METHODS: Sera from 86 RA patients and 90 control patients with other diseases, such as infections, connective tissue diseases, or other rheumatic diseases, were analysed using the four different methods. Specificity (84.4%) and PPV (80.3%) were lowest for RF IgM and highest for EliA CCP (specificity 97.8%, PPV 96.7%), the other values being close to those of EliA CCP. Sensitivity was highest for Quanta Lite CCP (73.3%). Efficiency was highest for Quanta Lite CCP (84.1%) at the lower cut off followed by EliA CCP at both cut offs (83.0%). The discrimination between RA sera (mean value 407.67 U/ml) and control sera (4.54 U/ml) and the relative risk (23.34) were best for EliA CCP. The results of this study reveal that there was no advantage of the anti-CCP antibodies assay applying a new antigen mixture (Quanta Lite CCP 3 ELISA) compared to two second generation anti-CCP antibodies assays (Quanta Lite CCP ELISA and EliA CCP).
17068699 Femoral head diameter affects the revision rate in total hip arthroplasty: an analysis of 2006 Oct BACKGROUND: In a previous study concerning 1,660 ScanHip THAs that were followed for up to 12 years, the cumulative revision rate was not found to be dependent on whether a 22-mm or a 32-mm head size had been used. We have re-examined these patients to see whether a longer follow-up time (9-21 years) would disclose an effect of head size on the revision rate. PATIENTS AND METHODS: We analyzed the cumulative revision rate for 1,720 Scan Hip arthroplasties with either 22-mm or 32-mm femoral heads. The patients were followed for 9-21 years. RESULTS: Arthroplasties with 32-mm head had 2.8-times higher cumulative revision rate than those with a 22-mm head. Older age reduced the risk of revision while male sex increased the risk. INTERPRETATION: We found that head size affects revision risk, but that even in a reasonably large material a long follow-up time is required to disclose the effects of head size--and thus wear--on survival.
18548358 [Results of extensor indicis transfer for reconstruction of the extensor pollicis longus t 2008 Jun Rupture of the extensor pollicis longus tendon is a frequent complication after distal radius fractures or other traumatic and non-traumatic events. Typical is the loss of the function of extension in the thumb. The extensor indicis transfer is a simple and effective technique for reconstruction of the extension with a low donor-site morbidity. We report on 38 patients with extensor indicis transfer. Postoperatively the patients received a dynamic motion splint for 4 weeks. For evaluation we have done pre- and postoperative ultrasound scans of the thumb, evaluated the DASH score and carried out a clinical examination.
17367694 Rheumatic diseases in the elderly: dealing with rheumatic pain in extended care facilities 2007 Feb Pain in elderly patients is often underreported, underdiagnosed, and undertreated. Increased understanding of the experience of pain in older persons, strategies for assessment, and appropriate use of pharmacologic and nonpharmacologic approaches is necessary to improve management of pain in this population. This article discusses how issues related to pain in the elderly should be approached, how elderly people perceive pain, how pain in the elderly is assessed, and the various pharmacologic and nonpharmacologic approaches for relieving pain. Finally, the article discusses how pain care for the elderly might be improved.
18407769 The recombinant humanized anti-IL-6 receptor antibody tocilizumab, an innovative drug for 2008 May BACKGROUND: IL-6 is a pro-inflammatory cytokine with multiple roles in the pathogenesis of rheumatoid arthritis (RA). Targeting IL-6 with the humanized anti IL-6 receptor antibody tocilizumab was effective in several placebo-controlled clinical studies in RA. OBJECTIVES: To address how clinically efficacious blockade of IL-6 signalling with inteleukin-6 receptor antibody is in RA patients and what the potential mode of action explaining tocilizumab activity in RA treatment could be. RESULTS/CONCLUSION: IL-6 induces autoantibody-producing plasma cells and effector T cells and is implicated in the development of clinical signs and symptoms, including increased synthesis of acute phase reactants, fatigue, anaemia and anorexia. Its effects also included significant improvements in American College of Rheumatology (ACR)20, ACR50 and ACR70 values, as well as in health-related quality of life measures, compared with controls. Tocilizumab also prevents radiographic progression of joint damage. Tocilizumab is generally well tolerated and efficacious in patients refractive to conventional DMARD therapies.
17404735 Synovial fluid and peripheral blood immune complexes of patients with rheumatoid arthritis 2007 Aug The destruction of cartilage is an important characteristic of rheumatoid arthritis (RA). Immune complexes (IC) are usually found in high amounts in RA synovial fluids (SF) and in the superficial layers of RA cartilage. The objective of this study was to investigate if IC have a direct influence on proliferation, survival and production of nitric oxide (NO) of cytokine-activated chondrocytes. Primary bovine chondrocytes were incubated with cytokines (huIL-1alpha, bovIFN-gamma, huTNF-alpha) and IC containing precipitates of peripheral blood (PB) and/or synovial fluid (SF) of 14 RA patients, 5 osteoarthritis (OA) patients and 10 healthy age and sex-matched controls. After 48 h, chondrocyte viability, proliferation, apoptosis, NO production and oxygen radical levels were measured. Staining with May-Grünwald-Giemsa after incubation with IC of RA PB and SF, showed apoptotic chondrocytes with condensation of the nuclei. The proliferation rates of cytokine-activated chondrocytes, incubated with sera and SF IC of RA patients were significantly decreased compared to chondrocytes, incubated with sera and SF IC of OA patients and compared to sera of controls. Quantitative evaluation of apoptotic cells by annexin-V/propidium iodide and TUNEL assays revealed a significant increase after incubation with sera and SF IC of RA patients, compared to control sera and OAs sera and SF. In all TUNEL positive samples, active-caspase-3-positive cells were found. There was a significant increase of chondrocyte NO production, after incubation with SF IC of RA patients, compared to OA SF. These results support the hypothesis that IC, present in serum and SF of RA patients, have a profound influence on chondrocyte growth, NO production and apoptosis, contributing to cartilage destruction in RA.
17694265 Higher maximal serum concentration of methotrexate predicts the incidence of adverse react 2007 Weekly pulsed low-dose methotrexate (MTX) is a standard regimen for rheumatoid arthritis (RA). Severe adverse reactions to MTX, such as pneumonia and cytopenia, sometimes occur; however, it is difficult to predict the development of these adverse reactions. In this article, we examine the serum concentrations of orally administered MTX of 69 Japanese patients with RA in the clinical setting. The maximum serum concentration (C (max)) after the first dose of the weekly administration and the time at which C (max) was obtained (T (max)) were analyzed. C (max) correlated with the administered dose before measurement. The average T (max) was 2.0 +/- 0.8 h, and none of the patients showed a T (max) of more than 4 h. In addition, we demonstrated that the weekly MTX dosage and the mean dosage of steroids were significantly higher in patients with adverse reactions than in those without them, and the C (max) after the first dose of the weekly administration particularly correlated with the incidence of adverse reactions (P < 0.001). In fact, the cut-off point of C (max) (0.16 micromol/l) was a sensitive predictor of the adverse reactions (sensitivity 81% and specificity 67%). We concluded that C (max) after the first dose of weekly administration is a useful parameter for predicting the development of adverse reactions to MTX.
16436036 Anti-TNF-alpha agents in the treatment of psoriatic arthritis. 2006 Feb Psoriatic arthritis (PsA) is a potentially debilitating disease that may affect small and large peripheral joints, entheses and the axial skeleton. The different clinical manifestations of PsA have been accounted for by various proposals of subdividing the patients into different subgroups. According to the predominant clinical symptoms, most patients can be classified as belonging to the spectrum of spondyloarthritides (SpA) or rheumatoid arthritis (RA). The conventional therapeutic approach comprises non-steroidal anti-inflammatory drugs, systemic and intra-articular corticosteroids, and disease-modifying antirheumatic drugs such as sulfasalazine, methotrexate, ciclosporin and leflunomide. Similar to RA, recent trials in PsA have shown excellent results with the tumour necrosis factor (TNF) blockers etanercept, infliximab and adalimumab, which have positive effects not only on joints, but also on the skin when affected by psoriasis, quality of life, function and slowing of disease progress, as evidenced radiologically. Anti-TNF therapy has been generally safe in clinical trials of PsA. Taken together, there has been definite recent progress in the treatment of PsA, especially for severely affected patients.
18050382 Clinical evidence for utilization of the A3 adenosine receptor as a target to treat rheuma 2008 Jan OBJECTIVE: Adenosine exerts antiinflammatory effects via activation of the A3 adenosine receptor (A3AR), a Gi protein-associated cell-surface receptor, overexpressed in synovial tissue and peripheral blood mononuclear cells (PBMC) in patients with active rheumatoid arthritis (RA). CF101 is a highly specific orally bioavailable A3AR agonist. METHODS: This was a multicenter study, blinded to dose, designed to assess the clinical activity and safety of CF101 in active RA. Seventy-four patients were randomized to receive 0.1, 1.0, or 4.0 mg CF101 bid for 12 weeks. The primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at Week 12. A3AR expression levels were analyzed in PBMC from 18 patients. RESULTS: . Maximal responses were observed with 1.0 mg bid, lower at 0.1 and 4.0 mg bid. At 12 weeks, 55.6%, 33.3%, and 11.5% of the patients receiving 1.0 mg CF101 achieved ACR20%, 50%, and 70% responses, respectively. CF101 was generally well tolerated, with mild headache (4.1%), nausea (2.7%), and rash (2.7%) being the most common treatment-related adverse events. Statistically significant correlations between A3AR overexpression at baseline and ACR50 and ACR70 responses were observed. CONCLUSION: CF101 administered bid for 12 weeks resulted in improvement in signs and symptoms of RA that did not achieve statistical significance, and was safe and well tolerated. The expression level of A3AR was directly correlated with patient responses to CF101, suggesting its utilization as a biomarker for the pharmacodynamic and therapeutic effects of this novel agent. These findings require confirmation in a double-blind randomized placebo-controlled trial, currently under way.
17405193 The early history of hand surgery in the Philippines and highlights in my experience at th 2006 Several years ago, while attending a Philippines Orthopaedic Association (PDA) Annual Convention, held at the Westin Philippine Plaza Hotel, Manila in December, I had the opportunity to meet with Professor Yoshikazu Ikuta, a well-known microsurgery and hand surgeon from Japan and one of the foreign guest speakers. I had been invited to work with him at the Armed Forces of the Philippines (AFP) Medical Center on the case of a high ranking general of the AFP, with a hand contracture disability problem. The case was referred to him by Dr. Evaristo Sanchez, Chief of Orthopaedics and the Commanding General of the AFP Medical Center. He had been pre-scheduled for surgery the next day, a Sunday morning, the day before Prof. Ikuta was due to return to Japan. After a brief examination and evaluation of the generals affected hand, in the operating room with Prof. Ikuta, just before he was placed under general anaesthesia, we performed the operation together. The operation did not involve microsurgery. The procedures done were multiple combined Bunnell-Zancolli pulley advancements and MP-joint volar capsulorraphies plus flexor tendon releases in the volar forearm, which although quite extensive, were only palliative, to minimise and improve on the contracture deformities, in preparation for a final re-evaluation for possible later, more definitive tendon transfers for hand function. However, I never received any further information regarding the results of our surgery. Recently, I have been honoured and invited again by Prof. Ikuta, presently the Editor-in-Chief of the Hand Surgery Journal (Asian Volume), this time to write the history of hand surgery in the Philippines and add to it, "Highlights in my experience at the National Orthopaedic Hospital, Mandaluyong, and the Our Lady of Lourdes Hospital, Manila", the last portion of which is on paralytic disabilities of the Hand. I am deeply grateful to Prof. Ikuta for giving me this honour and opportunity to present the total experience, favourable and unfavourable, of a hand surgeon from a developing country, like the Philippines. Furthermore, this would afford me also, the chance to be able to make known to readers of this now prestigious journal, the philosophical thoughts which led me to unwittingly originate or come up with and develop a few of my own "Long Tendon Rerouting Procedures" which may possibly and hopefully merit as this author's title contribution to surgery of the hands.
19046922 NF-kappaB modulators in osteolytic bone diseases. 2009 Feb Osteoclasts are responsible for bone resorption and play a pivotal role in the pathogenesis of osteolytic disorders. NF-kappaB is a set of nuclear factors that bind to consensus DNA sequences called kappaB sites, and is essential for osteoclast formation and survival. NF-kappaB signalling pathways are strictly regulated to maintain bone homeostasis by cytokines such as RANKL, TNF-alpha and IL-1, which differentially regulate classical and/or alternative NF-kappaB pathways in osteoclastic cells. These pathways are also modulated by NF-kappaB mediators, including TRAF6, aPKC, p62/SQSTM1 and deubiquitinating enzyme CYLD that are involved in the ubiquitin-proteasome system during RANK-mediated osteoclastogenesis. Abnormal activation of NF-kappaB signalling in osteoclasts has been associated with excessive osteoclastic activity, and frequently observed in osteolytic conditions, including periprosthetic osteolysis, arthritis, Paget's disease of bone, and periodontitis. NF-kappaB modulators such as parthenolide and NEMO-binding domain peptide demonstrate therapeutic effects on inflammation-induced bone destruction in mouse models. Unravelling the structure and function of NF-kappaB pathways in osteoclasts and other cell types will be important in developing new strategies for treatments of bone diseases.
16641042 Drug survival and reasons for discontinuation of intramuscular methotrexate: a study of 21 2006 Mar OBJECTIVES: To assess the drug survival and reasons for discontinuation of intramuscular methotrexate (imMTX) in rheumatological patients who had switched to imMTX from oral methotrexate (oMTX). METHODS: Data from 212 consecutive patients who switched from oMTX to imMTX therapy at our outpatient clinic between April 1997 and January 2004 were collected retrospectively through survey of case records. Data included reason for discontinuation of oMTX, disease activity parameters, duration of imMTX therapy, and, in patients who withdrew, the reason for discontinuation of imMTX. RESULTS: The main reasons for switching from oMTX to imMTX were lack of efficacy (66%) and adverse events (28%). After 6 months, 114 patients (54%) were still receiving imMTX therapy, and their median serum C-reactive protein (CRP) and the percentage of patients who had received glucocorticoids during the previous 6 weeks had decreased (p<0.001). The median survival of imMTX therapy was 7.5 months (interquartile range 3-17). Twenty per cent of the patients received imMTX for more than 24 months. Of the 212 patients, 41% and 9% stopped imMTX therapy because of lack of efficacy and adverse events, respectively. Of the patients who had stopped oMTX because of adverse events, 22% also withdrew from imMTX because of adverse events. CONCLUSION: Half of the patients benefited from switching from oral to intramuscular methotrexate for at least 6 months, but only a minority adhered to the treatment for years. Lack of efficacy was the most frequent reason for discontinuation, while adverse events were rare.
16360554 An investigation of clinical studies suggests those with multiple objectives should have a 2006 Jan BACKGROUND AND OBJECTIVES: Many clinical studies have more than one objective, either formally or informally, but this is not usually taken into account in the determination of the sample size. We investigated the overall power of a study, that is, the probability that all the objectives will be met. METHODS: We calculated the overall power in the case that the study has two primary outcome variables and in the case that one outcome variable is evaluated on two subsets, in particular, the Per Protocol group and the Intention to Treat group. RESULTS: A power of 80% for each of the two end points leads to poor power for the end points combined. However, a power of 90% preserves better the overall power. The power of the Per Protocol analysis can be higher or lower than the power of the Intention to Treat analysis. CONCLUSION: Power should be calculated for all end points combined, and it should be at least 90% for each primary end point. If the sample size for the intention-to-treat analysis is determined by adding a percentage of "nonevaluable subjects" to the sample size required for the per protocol analysis, then this may lead to an underpowered study.
16431349 Developing the concept of adoptive cellular gene therapy of rheumatoid arthritis. 2006 Feb Progressive destruction of articular cartilage and bone is the pivotal problem of rheumatoid arthritis (RA). Joint destruction is the cause of severe disability and determines the long-term outcome of disease. Conventional therapy does not control this destructive process sufficiently and the anti-rheumatic drugs available today can cause severe systemic adverse effects. Local application of chondroprotective and osteoprotective agents by means of gene therapy would be an attractive alternative to conventional therapy of RA and could provide long-term expression of the therapeutic agents and minimize systemic adverse effects. For this purpose, we have developed the concept of adoptive cellular gene therapy. This treatment strategy is based on using genetically engineered cells that home specifically to sites of autoimmune inflammation and thus allow local delivery of therapeutic gene products. Ex vivo transduction of these cells avoids systemic exposure of the host to the transgene-encoding vector and thus adds to the safety of this approach. In this article of the CIS Spring School in Autoimmune Diseases 2005 proceedings, we review our work on developing the strategy of adoptive cellular gene therapy and summarize recent advances in the evaluation of therapeutic effects and the identification of novel therapeutic targets.
16980409 Aberrant MHC class II expression in mouse joints leads to arthritis with extraarticular ma 2006 Sep 26 Genetic susceptibility to rheumatoid arthritis (RA) is associated with certain MHC class II molecules. To clarify the role of these determinants in RA, we generated the D1CC transgenic mouse that expressed genes involved in antigen processing and presentation by the MHC class II pathway in joints. The class II transactivator, which was transcribed from the rat collagen type II promoter and enhancer, directed the expression of these genes. In D1CC mice congenic for the H-2(q) (DBA/1) background, small amounts of bovine collagen type II in adjuvant induced reproducibly an inflammatory arthritis resembling RA. Importantly, these stimuli had no effect in DBA/1 mice. Eighty-nine percent of D1CC mice developed chronic disease with joint swelling, redness, and heat in association with synovial proliferation as well as pannus formation and mononuclear infiltration of synovial membranes. Granulomatous lesions resembling rheumatoid nodules and interstitial pneumonitis also were observed. As in patients with RA, anticyclic citrullinated peptide antibodies were detected during the inflammatory stage. Finally, joints in D1CC mice displayed juxtaarticular demineralization, severe joint space narrowing, and erosions, which led to ankylosis, but without the appearance of osteophytes. Thus, aberrant expression of MHC class II in joints facilitates the development of severe erosive inflammatory polyarthritis, which is very similar to RA.
16308341 Long term efficacy and safety of adalimumab plus methotrexate in patients with rheumatoid 2006 Jun OBJECTIVE: To evaluate the efficacy and safety of adalimumab plus methotrexate (MTX) given for up to 4 years in patients with active, longstanding rheumatoid arthritis. METHODS: Patients responding inadequately to MTX were entered into a 24 week, controlled study (ARMADA) with adalimumab plus MTX or placebo plus MTX, and some were enrolled in a subsequent open label extension. The efficacy and safety of treatment were evaluated. Additional analyses were made for those patients whose corticosteroid and/or MTX dosages were adjusted during the extension. RESULTS: Of 271 patients in the original ARMADA trial, 262 received at least one dose of adalimumab and were evaluated. At the time of analysis, 162/262 (62%) patients had remained in the study and received treatment for a mean of 3.4 years. Withdrawals were for lack of efficacy (8%), adverse events (12%), and other reasons (18%). In 147 patients who completed 4 years' treatment, efficacy achieved at 6 months was maintained. At 4 years, 78%, 57%, and 31% had achieved ACR20/50/70; 43% achieved clinical remission (DAS28 <2.6); and 22% had no physical function abnormalities (HAQ = 0). Results were similar for 196 patients who received treatment for 2-4 years. Efficacy was maintained in many patients when dosages were decreased (corticosteroids (51/81 (63%) patients), MTX (92/217 (42%)), or both (25/217 (12%))). Serious adverse events were comparable during open label treatment and the controlled phase. Serious infections occurring during open label treatment and the blinded period were similar (2.03 v 2.30 events per 100 patient-years, respectively). CONCLUSIONS: Adalimumab plus MTX sustained clinical response and remission in patients with RA during 4 years. The safety profile during the first 6 months was similar to that after 4 years' follow up. Reduction of corticosteroid and/or MTX dosages did not adversely affect long term efficacy.
16684367 Local treatment with the selective IkappaB kinase beta inhibitor NEMO-binding domain pepti 2006 Nuclear factor (NF)-kappaB is a key regulator of synovial inflammation. We investigated the effect of local NF-kappaB inhibition in rat adjuvant arthritis (AA), using the specific IkappaB kinase (IKK)-beta blocking NF-kappaB essential modulator-binding domain (NBD) peptide. The effects of the NBD peptide on human fibroblast-like synoviocytes (FLS) and macrophages, as well as rheumatoid arthritis (RA) whole-tissue biopsies, were also evaluated. First, we investigated the effects of the NBD peptide on RA FLS in vitro. Subsequently, NBD peptides were administered intra-articularly into the right ankle joint of rats at the onset of disease. The severity of arthritis was monitored over time, rats were sacrificed on day 20, and tissue specimens were collected for routine histology and x-rays of the ankle joints. Human macrophages or RA synovial tissues were cultured ex vivo in the presence or absence of NBD peptides, and cytokine production was measured in the supernatant by enzyme-linked immunosorbent assay. The NBD peptide blocked interleukin (IL)-1-beta-induced IkappaB alpha phosphorylation and IL-6 production in RA FLS. Intra-articular injection of the NBD peptide led to significantly reduced severity of arthritis (p < 0.0001) and reduced radiological damage (p = 0.04). This was associated with decreased synovial cellularity and reduced expression of tumor necrosis factor (TNF)-alpha and IL-1-beta in the synovium. Incubation of human macrophages with NBD peptides resulted in 50% inhibition of IL-1-beta-induced TNF-alpha production in the supernatant (p < 0.01). In addition, the NBD peptide decreased TNF-alpha-induced IL-6 production by human RA synovial tissue biopsies by approximately 42% (p < 0.01). Specific NF-kappaB blockade using a small peptide inhibitor of IKK-beta has anti-inflammatory effects in AA and human RA synovial tissue as well as in two important cell types in the pathogenesis of RA: macrophages and FLS. These results indicate that IKK-beta-targeted NF-kappaB blockade using the NBD peptide could offer a new approach for the local treatment of arthritis.