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Biomedical subjects

R Rau

Publications and source records attributed to R Rau.

At least 19 recordsLinked to original sources
PubMed2000

Response to methotrexate treatment is associated with reduced mortality in patients with severe rheumatoid arthritis.

OBJECTIVE: This study investigated whether efficacious methotrexate (MTX) treatment has an impact on mortality of patients with severe rheumatoid arthritis (RA). METHODS: In this prospective, observational, one-center study, patients with severe RA refractory to other disease-modifying antirheumatic drugs started MTX treatment between 1980 and 1987. Patients were divided into 4 different groups according to their response to MTX treatment after 1 year (>50% improvement [n = 99], 20-50% improvement [n = 70], no improvement [n = 52], and discontinued treatment [n = 35]). After a followup of 7.5-15.3 years (mean 10 years), the numbers of deaths were assessed in the different groups. Standardized mortality ratios (SMR) were calculated by comparing the number of observed deaths in the study with the number of expected deaths in an age- and sex-matched sample of the general population. RESULTS: Two hundred seventy-one patients entered the study between 1980 and 1987. In 1995/1996, outcomes for 256 patients (94.5%) could be documented; 88 patients (34.4%) had died. In patients with >50% improvement after 1 year, the SMR was 1.47, while in patients with 20-50% improvement, the SMR was 1.85. In both groups combined, the SMR was 1.64 (95% confidence interval [95% CI] 1.11-2.17), compared with 4.11 (95% CI 2.56-5.66) in patients without improvement. Patients who had discontinued MTX treatment during the first year had an SMR of 5.56 (95% CI 3.29-7.83). CONCLUSION: Patients with severe RA who do not respond to MTX treatment have a poor prognosis, with >4-fold increased mortality compared with the general population, while RA patients who respond to MTX treatment have only a moderately increased mortality rate.

Antirheumatic Agents↗
PubMed2000

[Concept for nationwide cooperation in planning and implementing multicenter studies].

In Germany, good clinical multicenter studies that are not supported by pharmaceutical companies are rarely performed. Good supranational industry-sponsored studies are usually aimed at the registration of new (expensive) drugs. The preconditions for co-operation in conducting industry-independent studies which are of interest for the scientific community have been improved substantially in Germany by instituting the working group of co-operating arthritis centers, the so-called core documentation where 32,000 patients with rheumatic conditions were documented in 1997 and the institution of a sophisticated information system ("RheumaNet"). The executive board of the German Rheumatology Association has set up an "ad hoc commission" that agreed to institute a "Committee for the Coordination of Clinical Studies in Rheumatic Diseases". In this committee rheumatologists subspecialized from medicine, orthopedic, pediatrics working in universities, hospitals and private practice as well as specialists in statistics and epidemiology shall be represented. In principle this committee is independent of the co-operating arthritis centers and the RheumaNet. All members of the German Rheumatology Association are invited to cooperate with this committee by contributing to the clinically important questions and participating in clinical studies. The committee has to define key questions in rheumatology and shall plan and organize multicenter studies to answer these questions. In addition, study protocols of pharmaceutical companies may be examined as to their importance, quality, and feasibility.

Antirheumatic Agents↗
PubMed2000

Low dose prednisolone therapy (LDPT) retards radiographically detectable destruction in early rheumatoid arthritis--preliminary results of a multicenter, randomized, parallel, double blind study.

OBJECTIVE: To test if continuous LDPT decreases radiographically detectable joint destruction in early RA. METHODS: Patients with active RA (< 2 years from symptom onset) were treated with prednisolone 5 mg daily or placebo for 2 years in a double blind, randomized, multi-center study. At the same time in all patients DMARD treatment with either gold sodium thiomalate (GSTM) or methotrexate (MTX) was started; in the case of side effects or inefficacy the medication could be switched to the other DMARD. Radiographs of hands and forefeet were taken at baseline and after 6, 12 and 24 months. All radiographs were evaluated by one observer (S.W.) knowing the time sequence of the film but unaware of the patient identity or treatment using the Ratingen score and van der Heijde's modification of Sharp's method. RESULTS: 196 patients were included; 76 patients completed the study per protocol. Of these patients 34 were treated with prednisolone, 42 with placebo, 48 initially with GSTM, 28 with MTX. 17 patients switched from GSTM to MTX, 1 from MTX to GSTM. The mean values of the radiographic scores of both groups are given in the table. During the first year, especially during the first 6 months, the radiographic progression within the prednisolone group was significantly lower than in the placebo group: the Sharp erosion score increased by 0.4% of the maximum possible score during the first and the second 6 months in the prednisolone group, while in the placebo group there was an increase of 1.8% during the first 6 months and 0.8% during the second 6 months. During the second year the progression was significantly lower (-0.1% in the prednisolone group, 0.2% in the placebo group). After 24 months the total score had increased by 2.6% of the maximum score in the placebo group and by 1.1% in the prednisolone group. The results of the completers were confirmed by the intention-to-treat analysis (80 patients in the prednisolone group, 86 patients in the placebo group). CONCLUSION: Continuous low dose prednisolone treatment with 5 mg daily over 2 years administered in addition to conventional DMARD treatment with MTX or GSTM decreases radiographic progression in early RA. The results of the study also show that in the placebo group there is a sharp decrease of the progression after 6-12 months as a result of the DMARD treatment. During the second year there is nearly no progression in this group. The data of the "completers" are confirmed by the analysis of the "intention to treat" population.

Adult↗
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↗