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ID PMID Title PublicationDate abstract
11199413 [Is open synovectomy of the metacarpophalangeal joint in chronic polyarthritis worthwhile? 2000 Nov PURPOSE/METHODS/PATIENTS: This work retrospectively analysed 252 synovectomies performed on 153 patients from 1958 to 1995 at the Balgrist University Orthopaedics Clinic, and evaluated the short-term and long-term benefits of open synovectomy of the metacarpo-phalangeal joint in rheumatoid arthritis. RESULTS: Rheumatoid arthritis (n = 182) was by far the most common of the 21 different diagnoses involved, and the metacarpo-phalangeal joint (n = 101) was by far the most frequently operated of the 7 different joint types in question. In the short tenn (n = 97), after a mean of 5.5 months, open synovectomy of a metacarpo-phalangeal joint in rheumatoid arthritis patients provided a benefit in terms of mobility in 85% of cases and in terms of joint swelling and pain in 93% of cases. Among one-third of the originally operated cases (n = 38), long-term benefit, i.e. after a mean of 6.9 years, was obtained in 89% of cases with regard to joint mobility, 87% with regard to swelling and 97% with regard to pain relief. Two-thirds of the joints presented normal mobility and swelling, and three-quarters were pain-free. CONCLUSIONS: The metacarpo-phalangeal joint is very important for maintaining the independence of a patient (gripping). Open synovectomy of the metacarpo-phalangeal joint in rheumatoid arthritis patients is an effective therapeutic procedure with little morbidity and very good long-term benefit in the management of metacarpo-phalangeal pain, swelling and stiffness refractory to conservative therapy.
10589367 Combination cyclosporine and (hydroxy)chloroquine in rheumatoid arthritis. 1999 Nov Antimalarials are attractive candidates for combination therapy. In vitro experiments have revealed a synergistic mode of action of cyclosporine and chloroquine which could not, however, be confirmed in a clinical trial.
9598881 Effect of vitamin D receptor gene alleles on bone loss in early rheumatoid arthritis. 1998 May OBJECTIVE: Rheumatoid arthritis (RA) is a polygenic disease characterized by localized joint destruction and generalized osteoporosis resulting in increased fracture risk. The pathogenetic mechanisms that determine the severity of generalized bone loss in RA are poorly understood. Polymorphisms in the vitamin D receptor (VDR) gene have been described as a significant determinant of bone turnover and mass. In this prospective study we describe VDR gene allele effects on bone loss in patients with early RA. METHODS: We recruited 232 patients with early RA. Bone mineral density measurements were repeated in 167 patients. Serial clinical and laboratory measures were recorded during the period of followup. DNA extraction, polymerase chain reaction amplification, and restriction fragment length polymorphism analysis of VDR alleles were performed using standard techniques. Presence of the Taq restriction site for both alleles was denoted "tt", and absence "TT". RESULTS: In women with RA the tt genotype group lost bone more rapidly than subjects with TT genotype at both the lumbar spine (-0.1 vs -4.9% p.a, respectively; p < 0.05) and femoral neck (-3.9 vs -9.6%, respectively; p < 0.01). The effect was independent of other disease characteristics. CONCLUSION: The presence of the VDR gene "t" allele in female patients with RA was associated with accelerated bone loss.
9926388 Dynamic motion analysis of normal and unstable cervical spines using cineradiography. An i 1999 Jan 15 STUDY DESIGN: Cervical motion patterns were analyzed in a normal population and in patients with cervical instability by using cineradiography. OBJECTIVES: To determine normal and pathologic motion patterns in the cervical spine through an in vivo continuous motion analysis. SUMMARY OF BACKGROUND DATA: Cineradiographic techniques have been used in a limited number of studies to quantify spinal motion. There is a paucity of information regarding dynamic motion patterns in normal and pathologic cervical spines. METHODS: Ten healthy subjects and 12 patients with unstable cervical spines (C1-C2 subluxation caused by rheumatoid arthritis, n = 10; instability below C2, n = 2) were studied. Cervical motion during flexion from the maximum extension position was recorded using cineradiography. Cervical segmental motions (C1-C2 to C5-C6) were continuously measured through quantifying cineradiographic images projected on a digitizer. RESULTS: Normal cervical spines showed a well-regulated stepwise motion pattern that initiated at C1-C2 and transmitted to the lower segments with time lags. Pathologic spines showed a different order of onset of segmental motion. In patients with rheumatoid arthritis who had atlantoaxial subluxation, C1-C2 motion initiated significantly earlier than C2-C3 motion. In patients with segmental instability below C2, motion in the unstable segments preceded that in the upper intact segments. CONCLUSIONS: Different motion patterns were observed between normal and pathologic cervical spines. Cineradiographic motion analysis is a valuable adjunctive technique, especially in diagnosis or evaluation of conditions that cannot be identified through conventional radiographic examination.
9776108 Efficacy of radiosynovectomy of the knee in rheumatoid arthritis: evaluation with magnetic 1998 The intra-articular injection of a radiopharmaceutical agent (radiosynovectomy) produces a reduction of the synovial inflammatory process. The inflammed synovial membrane can be identified with magnetic resonance imaging after the intravenous administration of gadolinium (MRI-Gd). A 6-month prospective study was carried out in 10 patients with rheumatoid arthritis after radiosynovectomy of the knee. The efficacy was evaluated with clinical parameters and MRI-Gd. A progressive amelioration of synovial effusion, pain, articular range of mobility, total leucocytes count in synovial fluid and synovial membrane thickness through MRI-Gd was observed. The global efficacy was considered to be good in six patients, fair in three and bad in one. The study shows for the first time that MRI-Gd allows the evaluation of the response of the synovial membrane to radiosynovectomy.
11764206 Comparative responsiveness of four elbow scoring instruments in patients with rheumatoid a 2001 Dec OBJECTIVE: This prospective study investigated the comparative responsiveness to change of 4 different elbow scoring instruments: 2 Hospital for Special Surgery elbow assessment scales, the Mayo Clinic Elbow Performance Index, and the Elbow Functional Assessment (EFA) Scale. METHODS: A group of patients with rheumatoid arthritis (RA) (median age 60 yrs) undergoing either elbow arthroplasty (22 elbows) or synovectomy with radial head excision (3 elbows) were evaluated both before and after surgery (median 7 mo postoperatively). Changes in the scores obtained using the scales under study were calculated and analyzed. The patient's opinion of global perceived effect of the intervention was used as an external criterion to classify them as "improved" or "non-changed." Responsiveness was evaluated with 3 different statistical approaches: using paired t statistics (pre and postsurgery scores), effect size statistics (standardized response mean, effect size, and responsiveness ratios), and receiver operator characteristic curves. Minimal clinically important difference was estimated using patient satisfaction as the external criterion. RESULTS: Each of the elbow rating measures under study proved to be responsive to change when evaluating patients with RA undergoing elbow arthroplasty or synovectomy. The EFA scale had the highest power to detect a clinically meaningful difference and had the best discriminative ability to distinguish improved from no-change patients, as shown by all responsiveness statistics applied. CONCLUSION: Using the EFA scale requires smaller sample sizes to achieve a fixed level of statistical power than the other scales we studied.
9588174 Isolation and characterization of a rheumatoid arthritis-specific antigen (RA-A47) from a 1998 Apr 28 Two types of 47 kDa antigen specifically recognized by sera from rheumatoid arthritis (RA) patients were isolated from the membrane fraction of a human chondrosarcoma-derived chondrocytic cell line (HCS-2/8) by a 2-step procedure: preparative SDS-PAGE and reverse-phase HPLC. An N-terminal amino acid sequence in one of the 47 kDa antigens, named RA-A47, had 81% homology to that deduced from the DNA sequence of the colligin gene which is reported as human hsp47 gene, and 100% homology to that deduced from the DNA sequence of colligin-2 gene, a homologue of colligin. The RA-A47 cross-reacted with a monoclonal antibody raised against chick heat shock protein (Hsp) 47 and bound to gelatin. The expression of the ra-a47 gene was enhanced by heat shock treatment and TGF-beta stimulation. These findings suggest that RA-A47 is a Hsp47-like protein, presumably the product of the colligin-2 gene, and that a collagen-specific molecular chaperone(s) such as Hsp47 and/or RA-A47 is involved in cartilage destruction in RA.
10410262 Evidence of disordered symptom appraisal in fibromyalgia: increased rates of reported como 1999 May OBJECTIVE: Using a large series of unselected consecutive patients, to investigate whether patients with fibromyalgia differ from those with rheumatoid arthritis (RA) or osteoarthritis (OA) in the number of reported comorbid conditions and in their perceived importance, and thereby to investigate differences in symptom appraisal and somatization. METHOD: In a clinical care setting, 1,298 patients with fibromyalgia and 2,396 with RA or OA participating in longitudinal data bank research as part of their routine medical care completed questionnaires concerning the presence or absence of 23 comorbid conditions, and then rated the current importance of each condition to them. Additional information concerning psychological factors and disease severity was also obtained. RESULTS: In analyses adjusted for age and sex, patients with fibromyalgia reported more conditions (4.5 vs. 3.1) than those with RA or OA. In 17 of 23 conditions, the condition was more commonly reported in fibromyalgia than in RA or OA. In 20 of the 23 conditions, the importance attached to the conditions by fibromyalgia patients exceeded that of the importance attributed by RA/OA patients. After adjustment for anxiety, statistical differences between the groups for importance was lost for 6 conditions. CONCLUSIONS: Fibromyalgia patients report more medical conditions and report that they are more important to them than do patients with RA or OA. These differences extend to conditions that might be expected to cause symptoms, as well as to those that are usually symptom free. These data suggest that, on average, patients with fibromyalgia appraise medical symptoms and their importance differently from patients with other rheumatic conditions.
10449169 Dendritic cells and the pathogenesis of rheumatoid arthritis. 1999 Aug Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease in which unknown arthrogenic autoantigen is presented to CD4+ T cells. The strong association of the disease with an epitope within the HLA-DR chain shared between various alleles of HLA-DR4 and DR1 emphasizes the importance of antigen presentation. This immune response predominantly occurs in the synovial tissue and fluid of the joints and autoreactive T cells are readily demonstrable in both the synovial compartment and blood. Circulating dendritic cells (DC) are phenotypically and functionally identical with normal peripheral blood (PB) DC. In the synovial tissue, fully differentiated perivascular DC are found in close association with T cells and with B cell follicles, sometimes containing follicular DC. These perivascular DC migrate across the activated endothelium from blood and receive differentiative signals within the joint from monocyte-derived cytokines and CD40-ligand+ T cells. In the SF, DC manifest an intermediate phenotype, similar to that of monocyte-derived DC in vitro. Like a delayed-type hypersensitivity response, the rheumatoid synovium represents an effector site. DC at many effector sites have a characteristic pattern of infiltration and differentiation. It is important to note that the effector response is not self-limiting in RA autoimmune inflammation. In this article, we argue that the presentation of self-antigen by DC and by autoantibody-producing B cells is critical for the perpetuation of the autoimmune response. Permanently arresting this ongoing immune response with either pharmaceutical agents or immunotherapy is a major challenge for immunology.
10833466 Cell cycle implications in the pathogenesis of rheumatoid arthritis. 2000 Jun 1 Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by hyperplasia of the synovial lining cells, angiogenesis, and infiltration of mononuclear cells resulting in pannus formation, cartilage erosion and ultimately joint destruction. Synovial tissue (ST) fibroblast hyperplasia is reminiscent of tumor-like proliferation and is a major cause of cartilage destruction in the RA joint. The RA joint is replete with cytokines and growth factors which exert a synergistic mitogenic effect on ST fibroblasts. As a result, RA ST fibroblasts exhibit elevated gene expression of proto- oncogenes, such as c-Myc, c-Ras, and c-Jun and apoptosis inhibitors such as Bcl-2. At the same time, RA ST fibroblasts contain mutations in tumor suppressor genes such as p53. The altered rates of proliferation and apoptosis of RA synovial cells result in the hyperplasia of synovial tissue and in concert with the chronic inflammatory environment ultimately lead to the destruction of the RA joint.
10796419 Cyclophosphamide for rheumatoid arthritis. 2000 OBJECTIVES: To estimate the short-term effects of cyclophosphamide for the treatment of rheumatoid arthritis. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's Register, the Cochrane Controlled Trials Register, Medline and Embase up to and including July 1997. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing oral cyclophosphamide against placebo (or an active drug at a dosage considered to be ineffective) in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: Data abstraction was carried out independently by two reviewers. The same two reviewers using Jadad's scale (Jadad 1995) assessed the methodological quality of the RCTs and CCTs. Rheumatoid arthritis outcome measures were extracted from the publications for baseline and end-of-study. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout. MAIN RESULTS: A total of 70 patients were included in the pooled analysis of two trials, 31 receiving cyclophosphamide. A statistically significant benefit was observed for cyclophosphamide when compared to placebo for tender and swollen joint scores: SMDs were -0.57 and -0.59 respectively. The difference in ESR also favoured the active drug but did not reach statistical significance (-12 mm, 95%CI: -26 to 2.5). One trial reported the number of patients developing new or worse erosions: the OR for cyclophosphamide compared to placebo was 0.17 (95% CI: 0.05 to 0.57). Patients receiving placebo were six times more likely to discontinue treatment because of lack of efficacy than patients receiving cyclophosphamide. Withdrawals from adverse reactions were higher in the cyclophosphamide group (Odds ratio=2.9), although this difference was not statistically significant. Side effects from cyclophosphamide included hemorrhagic cystitis, nausea, vomiting, leucopenia, thrombocytopenia, alopecia, amenorrhea and herpes zoster infections. REVIEWER'S CONCLUSIONS: Cyclophosphamide appears to have a clinically and statistically significant benefit on the disease activity of patients with RA, similar to some disease modifying antirheumatic drugs (DMARDs) such as antimalarials or sulfasalazine, but lower than methotrexate. Toxicity however is severe, limiting its use given the low benefit-risk ratio compared to other antirheumatic agents.
10332966 Arachidonate 15-lipoxygenase of reticulocyte-type in human rheumatoid arthritis type B syn 1999 May OBJECTIVE: Lipoxygenases (LOX) are lipid-peroxidating enzymes that are implicated in the pathogenesis of a variety of inflammatory disorders such as arthritis, psoriasis, and asthma. 15-LOX catalyzes the oxygenation of free arachidonic acid to 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE), which is reduced to 15-hydroxyeicosatetraenoic acid (15-HETE). The biological role of 15-HETE is less clear. We sought to determine if cultured human rheumatoid synovial cells were able to express 15-LOX mRNA, leading to the synthesis of 15-HETE, and to examine the effect of different cytokines on 15-LOX activity. METHODS: Adherent synovial cells were obtained by enzymatic digestion of rheumatoid synovium, isolated from patients with rheumatoid arthritis (RA) undergoing hip synovectomy. Between passages 4 and 8, reticulocyte-type 15-LOX expression in these cells was determined by reverse transcription-polymerase chain reaction (RT-PCR) in situ and confirmed by classical RT-PCR analysis followed by enzymatic digestion. The PCR fragment was purified, amplified, and sequenced. Cultured synovial cells were incubated with or without different cytokines and exogenous [1-(14)C] arachidonic acid metabolism of synoviocytes was analyzed by reverse phase high performance liquid chromatography (RP-HPLC). RESULTS: RT-PCR results showed that human RA type B synoviocytes expressed a reticulocyte-type 15-LOX. By sequence analysis, the PCR fragment (474 bp) was determined to be 100% identical to that of reticulocyte-type 15-LOX cDNA. Other results associated specific inflammatory cytokines with the activity of 15-LOX in these cells. RP-HPLC analysis showed that interleukin 4 (IL-4) increased 15-HETE production (2.4-fold); we also observed an increase in 15-HETE production (1.2-fold) after incubation of the cells with IL-1beta. CONCLUSION: Human RA type B synoviocytes are able to express 15-LOX mRNA leading to the synthesis of 15-HETE, which is modulated by various cytokines that play a major role in the pathophysiology of RA, especially IL-4 and IL-1.
9709183 Decreased serum apolipoprotein AII/AI ratio in systemic amyloidosis. 1998 Apr OBJECTIVE: To investigate if serum apolipoprotein A-I and A-II (apoAI and apAII) concentrations change in subjects with systemic amyloidosis secondary to underlying disorders. METHODS: Serum concentrations of apoAI and apoAII were measured in 21 multiple myeloma patients, including eight with amyloidosis; 95 rheumatoid arthritis patients, including 45 with amyloidosis; and 73 haemodialysis patients, including 32 with amyloidosis. RESULTS: ApoAII values tended to be reduced in subjects with amyloidosis in each group, but could not effectively distinguish amyloidosis. However, apoAII/AI ratios were significantly lower in subjects with amyloidosis in all groups. The ratio of 0.2 had diagnostic sensitivity and specificity for amyloidosis; 50% and 100%, respectively, in multiple myeloma; 80% and 78%, respectively, in rheumatoid arthritis; and 46% and 90%, respectively, in patients requiring long term haemodialysis. CONCLUSION: The apoAII/AI ratio can be a useful biochemical marker of suspect amyloidosis in patients with underlying diseases, especially those with rheumatoid arthritis.
10229396 Intraarticular variability of synovial membrane histology, immunohistology, and cytokine m 1999 Apr OBJECTIVE: To assess the variability of synovial histology, immunohistology, and cytokine mRNA expression at different sites within the knee joints of subjects with rheumatoid arthritis receiving slow acting antirheumatic drugs. The effects of intraarticular bupivacaine and adrenaline, and a comparison of synovial fluid cell and synovial membrane cytokine expression, were also investigated. METHODS: Arthroscopically directed synovial biopsies were taken at 3 or 4 predetermined sites from the knee joints of 11 patients. Histology for synovial lining layer, sublining cellularity and vascularity, and immunohistology for T cells, T cell subsets, and macrophages were assessed. Messenger RNA expression of interleukins 1beta, 2, 4, 6, 8, 10, granulocyte-monocyte colony stimulating factor, tumor necrosis factor-alpha, and interferon-gamma was detected using the reverse transcription/polymerase chain reaction technique. RESULTS: Synovial histology, immunohistology, and cytokine mRNA expression did not vary significantly. CD8 cell immunohistology was variable. Intraarticular bupivacaine and adrenaline did not change synovial characteristics. Synovial fluid cell and membrane cytokine expression did not match in 35% of comparisons. CONCLUSION: Biopsies from the suprapatellar pouch, medial gutter, and cartilage-pannus junction will provide a representative sample of synovial membrane pathology in patients with rheumatoid arthritis.
9546451 Non-constrained elbow arthroplasty for mutilans deformity in rheumatoid arthritis: a repor 1998 Mar Six highly unstable elbows with severe bone loss due to rheumatoid arthritis were replaced by a non-constrained, unlinked prosthesis. Bone defects were filled with autogenous bone grafts. The mean follow-up was 4.5 years (2 to 8). The clinical results were excellent in four elbows and good in two, with good varus-valgus stability in all. Radiological follow-up showed no appreciable signs of loosening, and the bone grafts had retained most of their original size, with minimal resorption. There were no major complications such as dislocation, skin necrosis, infection or ulnar neuropathy. The study has shown that the so-called mutilans elbow can be successfully replaced using a properly selected type of non-constrained, unlinked prosthesis with bone grafting of the major defects.
10955325 Longterm methotrexate use in rheumatoid arthritis: 12 year followup of 460 patients treate 2000 Aug OBJECTIVE: To extend our observations on the longterm tolerability of methotrexate (MTX) and reasons for discontinuation in a cohort of 460 patients with rheumatoid arthritis (RA). METHODS: We studied all patients with RA who started MTX before June 1986 and attended the community based private practices of 6 rheumatologists in Melbourne. Information to at least April 1, 1995, or within one year of death was updated from the patient's medical records to include MTX discontinuation and reasons for discontinuation. Addition of disease modifying antirheumatic drugs (DMARD) concomitant with MTX was noted. Survival analyses based upon life table methods were used with MTX discontinuation as the observable endpoint. Three different definitions of MTX discontinuation were used (1) according to whether the patient was taking the drug at last followup irrespective of any periods of temporary discontinuation; (2) MTX discontinuation for > 3 months considered to be a treatment endpoint; and (3) addition of concomitant DMARD considered to be only partial success of MTX (as a need for additional therapy to meet treatment goals). RESULTS: At 12 years, 53% of patients were continuing to take MTX (irrespective of any periods of temporary discontinuation). If discontinuation of the drug for 3 or more months was considered a treatment termination then 38% were still taking the drug at 12 years, and if addition of concomitant DMARD was regarded as a treatment endpoint only 17% of patients were continuing MTX at 12 years. Withdrawal for gastrointestinal toxicity declined over time but the risk of other adverse effects appeared to persist over time. CONCLUSION: MTX in RA is well tolerated over the longer term, with > 50% of patients starting MTX in a community based rheumatology private practice continuing to take it 12 years later. However, a substantial number of patients had 2nd line therapies added over this time. Monitoring for toxicity should continue throughout the course of therapy.
10525317 Flow cytometric detection of type 1 (IL-2, IFN-gamma) and type 2 (IL-4, IL-5) cytokines in 1999 Oct Type 1 cytokines (a.o. IL-2 and IFN-gamma) play an important role in the pathogenesis of rheumatoid arthritis. On the other hand, IgE-mediated diseases such as allergic asthma and atopic dermatitis show a type 2 cytokine (amongst others IL-4 and IL-5) profile. This study examined simultaneously the intracellular production of IL-2, IFN-gamma, IL-4 and IL-5 in T-lymphocytes of patients with rheumatoid arthritis during treatment with methotrexate or salazopyrin, patients with allergic asthma or atopic dermatitis under stable treatment, compared to healthy controls.A three-colour flow cytometric analysis was used for cytokine detection in T-helper cells and T-suppressor/cytotoxic cells. Compared to controls, patients with symptomatic atopic dermatitis showed an increased number of IL-4-producing T-helper lymphocytes in basal circumstances (P=0.001), in contrast to asymptomatic allergic asthma patients. Compared to controls, rheumatoid arthritis patients, treated with salazopyrin, showed an increased number of IL-2-producing T-helper and T-suppressor/cytotoxic lymphocytes after in vitro stimulation with PMA and ionomycin (P=0.01). In contrast, rheumatoid arthritis patients, treated with methotrexate, a more potent disease modifying drug, did not show this type 1 cytokine profile. A positive correlation was found between the number of IFN-gamma producing T-helper cells and disease activity (Ritchie Index and number of swollen joints) in both rheumatoid arthritis patient groups. Active atopic dermatitis patients showed a type 2 cytokine profile, whereas stable asthma patients with lower disease activity did not show a predominance of type 2 cytokines. Rheumatoid arthritis patients under treatment with salazopyrin had a type 1 cytokine profile, which could not be demonstrated in patients treated with methotrexate. This imbalance between type 1 and type 2 cytokines in different immune mediated disorders can be related with treatment and the grade of disease activity. These results stress the need for further investigation of the influence of therapy on cytokine profiles.
10949718 Clinical effects of actarit in rheumatoid arthritis: improvement of early disease activity 2000 Jul OBJECTIVE: We previously reported the presence of high serum concentrations of nitric oxide (NO) in patients with rheumatoid arthritis (RA). In this study we evaluated the effect of actarit on patients with early and advanced stages of RA and the relationship between RA activity and serum NO levels. METHODS: Thirty-seven RA patients who were undergoing care at Sasebo Chuo Hospital were entered into the study. Patients were divided into two groups based on the severity of their disease: group I (stages I and II) and group II (stages III and IV). NO concentrations in serum samples were measured by the chemiluminescence method. RESULTS: Morning stiffness, the number of tender and swollen joints, grip strength, pain score, modified Health Assessment Questionnaire score (mHAQ), ESR, CRP and the Lansbury index significantly improved during 24 weeks of treatment in group I. Patients in group II did not show improvement in morning stiffness, pain score, ESR or CRP during treatment. The concentrations of NO in group I were significantly reduced at 8 weeks after administration of actarit. Those in group II showed a delayed response; a significant decrease in NO occurred at 20 weeks. The improvement in the number of tender and swollen joints, grip strength, pain score, mHAQ and Lansbury index noted in group I preceded the fall in NO concentrations. CONCLUSION: Our results demonstrate that actarit improves disease activity in early phase RA by suppressing serum NO levels. The results suggest that NO is a useful marker for monitoring improvement in the early stages of RA.
9458199 Flare during drug withdrawal as a method to support efficacy in rheumatoid arthritis: amip 1998 Jan OBJECTIVE: To evaluate the use of a randomized, double blind, drug withdrawal design as a means to test the efficacy of longterm therapy with antirheumatic drugs. METHODS: We evaluated 286 patients with rheumatoid arthritis (RA) treated with amiprilose hydrochloride for 1-3 years, with response, with or without other antirheumatic therapy, in a double blind, 12 week withdrawal study that compared patients randomized to continue amiprilose therapy vs patients randomized to placebo. The primary efficacy variable was preventing a predefined degree of clinical reactivation, or flare; the statistical tests of success were a difference in the proportion of flares and in the mean time to flare. RESULTS: Thirty percent of patients taking amiprilose and 43% of placebo patients experienced flare (p = 0.026). Patients taking amiprilose had a longer flare-free interval compared to placebo patients (p = 0.027), with the time to reactivation or flare becoming statistically different 73 days after withdrawal. CONCLUSION: Placebo controlled withdrawal designs are useful as evidence to support the longterm effectiveness of therapy in a proportion of patients with RA.
10220832 Gly-X-Y repeat sequences in the treatment of active rheumatoid arthritis. 1999 The aim of the present study was to examine if oral administration of Gly-X-Y repeat sequences alleviates disease activity in rheumatoid arthritis (RA). The study had a randomized, placebo controlled and double blind design with a wash-out/cross-over between the two 3-months long treatment periods. A total of 40 patients entered and 36 patients fulfilled the study, among them 16 started with the active drug and 20 with a placebo. Disease activity score (DAS) was used as the primary outcome measure with several secondary outcome variables. Type I or alpha error of 0.05 was accepted and the power (= 1-beta) was set to 80%, which according to the power analysis was also achieved. With active drug treatment, joint swelling score (54 count; P < 0.001), Ritchie's index (P < 0.01) and DAS (P < 0.001) improved. HAQ also improved (P < 0.05), but there was no improvement in the subjective condition of the patients as measured with the self-reported Pain Disability Index and Comprehensible Psychopathological Rating scale questionnaires. Apparently, 5/36 patients had a response of > or = 1.2 in DAS and 33/36 changed for the better; DAS impaired only in 3/36 patients during the active drug treatment When the stringent EU response criteria were applied and the results were compared to the placebo group, the response was not clinically significant. We conclude that Gly-X-Y repeat sequences are not effective as used in the present study. However, this does not definitely disprove the value of the Gly-X-Y repeat sequences, because confounding effects of dosage, concomitant medication and excessive degradation of the linear Gly-X-Y sequences in the stomach, gut or by phagolysosomes could not be adequately controlled. The discrepancy between the favourable effects in the preliminary, open pilot study and the controlled clinical trial emphasizes the value of the DAS, EU response criteria and adequately administered controlled clinical studies.