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Biomedical subjects

R Rau

Publications and source records attributed to R Rau.

At least 55 records · Page 3Linked to original sources
PubMed2000

HLA-DRB1 genes, rheumatoid factor, and elevated C-reactive protein: independent risk factors of radiographic progression in early rheumatoid arthritis. Berlin Collaborating Rheumatological Study Group.

OBJECTIVE: To evaluate the prognostic value of HLA-DRB1 antigens, rheumatoid factor (RF), and C-reactive protein (CRP) with the radiographic outcome of rheumatoid arthritis (RA). METHODS: In total, 139 patients with early RA (< 2 years) were followed up. At the end of 3 year treatment with disease modifying antirheumatic drugs (DMARD) HLA genotyping and external radiographic scoring were performed. The time up to the first development of erosive disease [Ratingen radiographic score (RS) > 0, > 5, > 10] was compared by methods of survival analysis. RESULTS: At 4 years' disease duration, DRB1*04 or DRB1*01 positive patients had RS > 0 or > 10 (73% and 27%, respectively) significantly more frequently than DRB1*04 or DRB1*01 negative patients (37% and 7%, respectively). Nearly independently of the genetic predisposition, RF and elevated CRP at the start of DMARD treatment were predictive for erosive RA at 4 years. Elevated CRP (> or = 15 mg/l) increased the probability of erosive RA in DRB1*04 or DRB1*01 positive patients from 64.0% (in patients with CRP < 15 mg/l) to 83.9%, and in DRB1*04 and DRB1*01 negative patients from 18.8% to 70.1%. The corresponding figures for RF+ and RF- patients were 58.2% and 82.5% in HLA predisposed patients and 23.5% and 60.2% in those who were negative for DRB1*04 and DRB1*01. The probability of a RS > 10 was 40.9% for HLA predisposed patients with elevated CRP. In contrast, no case with RS > 10 was found in 43 patients who had neither of these 2 risk factors. CONCLUSION: Our findings support that HLA predisposition plays an important role with regard to radiographic progression. However, this effect is modified by RF serum concentration and disease activity.

Arthritis, Rheumatoid↗
PubMed2000

The effect of HLA-DRB1 genes, rheumatoid factor, and treatment on radiographic disease progression in rheumatoid arthritis over 6 years.

OBJECTIVE: To investigate the relationship between radiographic disease progression in the presence or absence of rheumatoid arthritis (RA) linked HLA-DRB1 alleles after early introduction of disease modifying antirheumatic drug therapy in patients with RA over a study period of 6 years. METHODS: One hundred nine patients of a trial comparing intramuscular (im) gold sodium thiomalate (GSTM) and im methotrexate (MTX) in early erosive RA were followed for 6 years with regular assessments of clinical and laboratory data and yearly radiographs of hands and feet, and they were typed for HLA-DRB1 genes. Radiographic progression was analyzed for an influence of rheumatoid factor (RF) status and HLA-DRB1 genes. RESULTS: Twenty-seven patients (25%) were positive for two, 46 (42%) for one, and 36 (33%) for none of the disease linked alleles. A decrease of the rate of radiographic disease progression with treatment in this group of patients was reflected by the decline in the slope of the radiographic score. Seropositive patients (n = 71, 68%) had a significantly more destructive disease course than RF negative patients. In seropositive disease, patients with a "double dose" of RA linked alleles showed a tendency to greater progression during the first 12-24 mo of treatment, but no significant difference in the longterm radiographic outcome could be detected between subgroups defined by the presence or absence of HLA-DRB1 genes. There was no significant difference throughout the study period with respect to the clinical disease course as assessed by joint swelling, C-reactive protein, and erythrocyte sedimentation rate. The majority of the seronegative population (n = 38, 32%) had a benign disease course with the exception of patients (n = 6) with the double allele; they had radiographic disease progression comparable with the seropositive patients. CONCLUSION: Our data do not provide evidence for a more aggressive disease course in patients bearing double RA linked HLA-DRB1 alleles.

Alleles↗
PubMed1999

Reliability and sensitivity to change of a simplification of the Sharp/van der Heijde radiological assessment in rheumatoid arthritis.

OBJECTIVE: To determine the reliability and sensitivity to change of a simplified radiological scoring method [simple erosion narrowing score (SENS)] for rheumatoid arthritis (RA). SENS was compared to the Sharp/van der Heijde score (SHS) as a gold standard. METHODS: Sets of seven radiographs of hands and feet were taken of 20 RA patients with a wide spectrum of radiological damage. For 14 patients, these seven radiographs were taken during a follow-up period of 5 yr, and for six patients during a follow-up of 10 yr. Each set of radiographs was scored twice by the same observer (DvdH). Erosions and joint space narrowing were scored with SHS (range 0-448) in 32 and 30 joints in the hands, respectively, and both in 12 joints in the feet. SENS gives a score of 1 if there is any erosion in a joint and also 1 if there is any narrowing in the joint (range 0-86). In each case, SENS was derived from SHS. To analyse data, generalizability theory and repeated measurements ANOVA were used. RESULTS: The overall reliability coefficient was 0.81 for SHS and 0.80 for SENS. Intra-observer reliability [intraclass correlation coefficient (ICC)] was 0.99 and 0.98 for SHS and SENS, respectively. The ICC for the sensitivity to change was 0.84 for SHS and 0.88 for SENS. The smallest detectable difference (SDD) could be determined for both methods. The presence of progression based on this SDD was very comparable between the two methods. CONCLUSION: The measurement properties of SENS are good and comparable to SHS. This makes SENS suitable for use in clinical practice and in large (epidemiological) studies, especially in the first years of disease.

Adult↗
PubMed1999

Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components.

OBJECTIVES: To investigate the potential clinical benefit of a combination therapy. METHODS: 205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying antirheumatoid drugs previously, with an early (< or = 1 year duration), active (Disease Activity Score (DAS) > 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68). RESULTS: The mean changes in the DAS during the one year follow up of the study was -1.15, -0.87, -1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007). CONCLUSION: This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable.

Antirheumatic Agents↗
PubMed1999

Prospective six year follow up of patients withdrawn from a randomised study comparing parenteral gold salt and methotrexate.

OBJECTIVE: To confirm the impression of a better outcome of patients withdrawn from parenteral gold salt therapy compared with those withdrawn from methotrexate. METHODS: Patients with early, active, and erosive RA were randomised for a double blind trial to receive either weekly 15 mg intramuscular methotrexate or 50 mg goldsodiumthiomalate. If the drug had to be withdrawn because of side effects treatment was continued with the other drug in still active disease. Patients with insufficient response were treated with a combination of both drugs. All patients were followed up by an extended clinical and radiographic evaluation. RESULTS: 64 patients each were allocated to methotrexate and gold treatment. After 72 months a complete record was available for 88% of patients. Within the first 36 months 38 patients withdrew from gold treatment (95% because of side effects) and 23 patients withdrew from methotrexate (57% because of side effects). A significant 40% to 70% improvement of all parameters (erythrocyte sedimentation rate, C reactive protein, swollen and tender joints, radiological progression) compared with baseline was observed in patients completing their randomised treatment with gold or methotrexate. The same improvement over three years was seen in patients who withdrew from gold treatment, while patients withdrawing from methotrexate experienced a deterioration of their disease. CONCLUSION: Withdrawals represent the majority of patients in long term drug trials. Patients with early RA stopping gold because of side effects show almost the same sustained improvement as patients continuing gold or methotrexate. Patients withdrawn from methotrexate experience a reactivation of their disease.

Antirheumatic Agents↗
PubMed1999

Imaging in rheumatoid arthritis: results of group discussions.

None of the current scoring methods for radiological damage in rheumatoid arthritis (RA) is ideal. The objective for RA imaging at OMERACT IV was to start discussion about the problems and applicability of the current scoring methods for radiological damage and to start discussion on the challenge of new imaging techniques. The RA imaging module comprised preconference reading material, plenary sessions, small group discussions, and a plenary report of the group sessions, combined with interactive voting. The OMERACT filter guided the discussions. Priorities for further research in imaging studies were: (1) pathologies versus features on radiographs; (2) relation with longterm outcome; and (3) definition of minimum clinically important difference.

Arthritis, Rheumatoid↗
PubMed1998

Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist.

OBJECTIVE: To evaluate the efficacy and safety of interleukin-1 receptor antagonist (IL-1Ra) in patients with rheumatoid arthritis (RA). METHODS: Patients with active and severe RA (disease duration <8 years) were recruited into a 24-week, double-blind, randomized, placebo-controlled, multicenter study. Doses of nonsteroidal antiinflammatory drugs and/or oral corticosteroids (< or =10 mg prednisolone daily) remained constant throughout the study. Any disease-modifying antirheumatic drugs that were being administered were discontinued at least 6 weeks prior to enrollment. Patients were randomized to 1 of 4 treatment groups: placebo or a single, self-administered subcutaneous injection of IL-1Ra at a daily dose of 30 mg, 75 mg, or 150 mg. RESULTS: A total of 472 patients were recruited. At enrollment, the mean age, sex ratio, disease duration, and percentage of patients with rheumatoid factor and erosions were similar in the 4 treatment groups. The clinical parameters of disease activity were similar in each treatment group and were consistent with active and severe RA. At 24 weeks, of the patients who received 150 mg/day IL-1Ra, 43% met the American College of Rheumatology criteria for response (the primary efficacy measure), 44% met the Paulus criteria, and statistically significant improvements were seen in the number of swollen joints, number of tender joints, investigator's assessment of disease activity, patient's assessment of disease activity, pain score on a visual analog scale, duration of morning stiffness, Health Assessment Questionnaire score, C-reactive protein level, and erythrocyte sedimentation rate. In addition, the rate of radiologic progression in the patients receiving IL-1Ra was significantly less than in the placebo group at 24 weeks, as evidenced by the Larsen score and the erosive joint count. IL-1Ra was well tolerated and no serious adverse events were observed. An injection-site reaction was the most frequently observed adverse event, and this resulted in a 5% rate of withdrawal from the study among those receiving IL-1Ra at 150 mg/day. CONCLUSION: This study confirmed both the efficacy and the safety of IL-1Ra in a large cohort of patients with active and severe RA. IL-1Ra is the first biologic agent to demonstrate a beneficial effect on the rate of joint erosion.

Adolescent↗
PubMed1998

[Is H15 (resin extract of Boswellia serrata, "incense") a useful supplement to established drug therapy of chronic polyarthritis? Results of a double-blind pilot study].

BACKGROUND: Leukotrienes and prostaglandines are important mediators of inflammation. While prostaglandine synthesis can be influenced by NSAIDs therapeutical approaches to the 5-lipoxygenase pathway are rare. Resinous extracts of Boswellia serrata (H15, indish incense), known from traditional ayurvedic medicine, decrease leukotriene synthesis in vitro. Case reports suggest a clinical role for that drug. METHODS: Outpatients with active RA have been enrolled into a multicenter controlled trial. Patients received 9 tablets of active drug (3600 mg) or placebo daily in addition to their previous therapy. Doses of NSAIDs could be adjusted on demand. Efficacy parameters, Ritchies Index for swelling and pain, ESR, CRP, pain on VAS and NSAID dose were documented at baseline and 6 and 12 weeks after initiation. Mean values and medians were calculated to compare the groups for significant or clinically relevant change from baseline or difference between both groups at any time point of observation. RESULTS: A total of 78 patients were recruited in 4 centers, the data have been published in abstract form. Only 37 patients (verum 18, placebo 19), enrolled in Ratingen were available for detailed efficacy and safety analysis. All evaluations in these patients were performed by one investigator (G.H.). There was no subjective, clinical or laboratory parameter showing a significant or clinically relevant change from baseline or difference between both groups at any time point of observation. The mean NSAID dose reduction reached levels of 5.8% (H15) and 3.1% (placebo). One patient in each group showed a good response in all parameters but 4 patients in each group worsened. The others showed no alteration of their disease. CONCLUSION: Treatment with H15 showed no measurable efficacy. Controlled studies including a greater patient population are necessary to confirm or reject our results.

Adult↗
PubMed1998

[Concomitant manifestation of ochronosis and chronic polyarthritis in a patient].

Ochronosis is rare disorder of tyrosin catabolism with an autosomal, recessive trait. Clinical signs predominantly affect the locomotor system. Inflammatory episodes in large joints can mimick Rheumatoid Arthritis (RA). Brownish discoloration of sclerae and cartilage is characteristic, diagnosis is confirmed by typical changes of spinal X-rays and the findings of homogentisic acid in urine samples. We describe a case of a 53 year old female patient with ochronosis and a second diagnosis of RA.

Arthritis, Rheumatoid↗
PubMed1998

[Therapy of refractory chronic polyarthritis with tumor necrosis factor alpha receptor fusion proteins (TNFR55-IgG1)--results of double-blind placebo-controlled studies over 3 months].

UNLABELLED: AIM OF STUDIES: To determine the optimal dose regimen for i.v. TNFR55-IgG1 in refractory rheumatoid arthritis. METHODS: 218 patients with refractory rheumatoid arthritis were enrolled for two double-blind placebo-controlled multicenter trials (Europe and USA). They were treated with monthly i.v. placebo, 0.01, 0.05, 0.1 or 0.5 mg/kg TNFR55-IgG1 after a 4 week wash-out of DMARDs. An additional German trial compared biweekly i.v. 20 mg TNFR55-IgG1 and monthly 50 mg following a loading does of 100 mg in 60 patients. RESULTS: TNFR55-IgG1 induced a substantial improvement already apparent one day after the first infusion. A maximal, dose dependent effect was reached after two weeks. Later, efficacy declined in parallel to an increase in anti-TNFR55-IgG1 antibodies resulting in an increased drug clearance. The drug was well tolerated with predominantly mild or moderate adverse events. CONCLUSION: Intravenous TNFR55-IgG1 was well tolerated and effective in refractory rheumatoid arthritis but the treatment schedules tested could not stabilise the initial improvement.

Adult↗
PubMed1998

[Therapy of refractory chronic polyarthritis with tumor necrosis factor alpha receptor fusion protein (TNFR55-IgG1)--long term follow-up of 80 personal cases].

AIM OF THE STUDY: To investigate the long-term effect of TNFR55-IgG1 in patients with severe rheumatoid arthritis refractory to multiple previous DMARD treatments. METHODS: Between 1994 and 1995 we recruited 80 patients for two double blind, placebo-controlled multicenter trials. All patients were treated for 2-30 months with a glycosylated fused protein consisting of two human p55 TNF receptors linked to a human IgG1-Fc. The dose range was 2.5-100 mg/month given i.v. with cumulative doses from 40-940 mg. All patients were followed-up prospectively for 24-36 months after initiation of therapy. The evaluations included a 48 swollen and tender joint count, ESR. CRP, RF, ANA, ENA, and safety parameters at 6 month intervals. In addition, pharmacokinetics, TNF, and anti-TNFR55-IgG1 antibody levels were available after the first and third injection. RESULTS: Data from 80 patients are available representing an experience of more than 170 patient years; 11 patients are still being treated. Predominant reasons for treatment withdrawal were restrictions in treatment protocol. Six patients died (1 during treatment, 5 in the post-treatment follow-up). All deaths were related to preexisting cardiovascular disease except one post-surgery septic arthritis 6 months after the last dosing (during vacation in another country). No malignancies were detected. Anti-TNFR55-IgG1 antibodies correlated with a decrease in drug half-time. Shifts in the TNFR55-IgG1 glycosylation pattern affected pharmacokinetics and efficacy. A lupus nephritis occurred 18 months after the last dosing in one patient with erosive RA (ANA and dsDNS positive already before TNFR55-IgG1 initiation). Continued treatment for 3 years in 11 patients resulted in an 81% reduction in swollen joint count, less morning stiffness, less pain, and a reduction in steroids. CONCLUSION: Treatment with TNFR55-IgG1 is safe and efficacious over the long-term in patients with severe refractory RA.

Adult↗
PubMed1998

[Quality management in the interdisciplinary specialty hospital].

The aim of quality management in rheumatology is to improve care and outcome in patients with rheumatic diseases. This can be achieved by means of prospective long-term observation of the patient with regular documentation of clinical, radiological, biochemical and functional data using certain validated scoring methods (DAS, radiological score, ADL score Hanover or Health assessment questionnaire, SF36, etc.). Long-term observation and documentation including radiographs have been performed in the rheumatology hospital in Ratingen for 20 years without even knowing the term quality management. Quality management in a hospital for rheumatic diseases begins with certain structural prerequisites: possibility of direct admission of a patient to the hospital by the family physician, outpatient clinic to investigate and to follow patients over a long period of time, multidisciplinary team with specialists in rheumatology, orthopedic surgery, physiotherapy, ergotherapy, special care, psychological, and social services, close cooperation with specialists in neurology, dermatology, ophthalmology, etc., department of radiology, special laboratory, facilities for internal diagnostic and treatment. The hospital needs a training program for the qualification of rheumatologists and orthopaedic surgeons. The hospital staff should closely cooperate with the doctors in private practice who admit patients and should continuously support patient organizations. The quality of outcome is influenced by the process quality which depends on the following factors: selection, training and motivation of the hospital staff; supervision of clinical assessment and documentation by senior physicians, daily x-ray demonstrations and case reports, interdisciplinary case demonstrations at least every week in addition to daily consultation, team reports, regular education including review of actual literature for physicians, education programs exchanging knowledge with physiotherapists and nurses, and regular education programs for patients. Process quality can only be achieved by an interdisciplinary approach and regular communication between all participants including the patient, whose opinion must be noted and regarded. As far as possible, the same doctor who treats the patient in the hospital should follow her/him in the outpatient clinic. The quality of outcome can be improved by regular reinvestigation of the patient with control of medication, side effects, efficacy, documentation of clinical, biochemical, radiological, and functional data. Decisions for further treatment have to be based on these follow-up data. A standardized follow up and documentation system for all rheumatology units with prompt feedback could definitely improve the quality of rheumatologic care in Germany.

Aftercare↗