The efficacy of anti-TNF in rheumatoid arthritis, a comparison between randomised controlled trials and clinical practice.

BACKGROUND: Randomised controlled trials (RCTs) evaluating the efficacy of antagonists to tumour necrosis factor alpha (TNFalpha) showed high response percentages in the groups treated with active drugs. OBJECTIVE: To compare the efficacy of anti-TNF treatments for rheumatoid arthritis (RA) patients in RCTs and in daily clinical practice, with an emphasis on the efficacy for patients eligible and not eligible for RCTs of anti-TNF treatments. METHODS: First, randomised placebo-controlled trials written in English for etanercept, infliximab and adalimumab for patients with RA were selected by a systematic review. Second, the DREAM (Dutch Rheumatoid Arthritis Monitoring) register with patients starting for the first time on one of the TNF-blocking agents was used. Patient characteristics, doses of medication and co-medication as well as the ACR20 response percentages were compared between RCTs and DREAM data, stratified for trial eligibility. RESULTS: In 10 of 11 comparisons, the ACR20 response percentages were lower in daily clinical practice than in the RCT active drug group, which was significant in five of 11 comparisons. Only 34-79% of DREAM patients fulfilled the selection criteria for disease activity in the several RCTs examined. DREAM patients eligible for RCTs had higher response percentages than ineligible DREAM patients. ACR20 response percentages of eligible DREAM patients were comparable with the ACR20 response percentages of the RCT active drug group in 10 of 11 comparisons. CONCLUSION: The efficacy of TNF-blocking agents in RCTs exceeded the efficacy of these drugs in clinical practice. However, in clinical practice more patients with lower disease activity were treated with TNF-blocking agents compared with those treated in RCTs. For daily practice patients who were eligible for RCTs, responses were more similar to responses reached in RCTs.

Evidence for familial aggregation of hand, hip, and spine but not knee osteoarthritis in siblings with multiple joint involvement: the GARP study.

OBJECTIVE: To evaluate whether familial aggregation of osteoarthritis differs by joint site in a sibling pair study (GARP) of patients with osteoarthritis at multiple sites. SUBJECTS: White Dutch probands aged 40 to 70 years and their siblings with primary osteoarthritis at multiple sites. METHODS: The diagnosis of knee, hip, and spine osteoarthritis was based on a combination of pain or stiffness on most days of the previous month and osteophytes or joint space narrowing on x ray. Hand osteoarthritis was defined by ACR criteria. Odds ratios (OR) were calculated for siblings and probands sharing disease in the same joints. RESULTS: 191 sibling pairs were included (85% women; mean age 60 years). In the probands, osteoarthritis was present in spine (76%), hands (77%), knees (37%), and hips (26%). The most common combinations in probands were spine-hand (59%), spine-knee (27%), and hand-knee (25%). The OR adjusted for age, sex, and body mass index for siblings to be affected in the same joint sites as the proband were increased in osteoarthritis of the hand (OR = 4.4 (95% confidence interval, 2.0 to 9.5)), hip (OR = 3.9 (1.8 to 8.4)), spine (OR = 2.2 (1.0 to 5.1)), hip-spine (OR = 4.7 (2.1 to 10.4)), and hand-hip (OR = 3.4 (1.1 to 10.4)). Siblings of probands with osteoarthritis in the knee did not have an increased likelihood of knee osteoarthritis. CONCLUSIONS: In middle aged patients with familial osteoarthritis at multiple sites, familial aggregation of osteoarthritis was most striking for hand and hip but remarkably absent for the knee.

Long term high intensity exercise and damage of small joints in rheumatoid arthritis.

OBJECTIVE: To investigate the effect of long term high intensity weightbearing exercises on radiological damage of the joints of the hands and feet in patients with rheumatoid arthritis (RA). METHODS: Data of the 281 completers of a 2 year randomised controlled trial comparing the effects of usual care physical therapy (UC) with high intensity weightbearing exercises were analysed for the rate of radiological joint damage (Larsen score) of the hands and feet. Potential determinants of outcome were defined: disease activity, use of drugs, change in physical capacity and in bone mineral density, and attendance rate at exercise sessions. RESULTS: After 2 years, the 136 participants in high intensity weightbearing exercises developed significantly less radiological damage than the 145 participants in UC. The mean (SD) increase in damage was 3.5 (7.9) in the exercise group and 5.7 (10.2) in the UC group, p = 0.045. Separate analysis of the damage to the hands and feet suggests that this difference in rate of increase of damage is more pronounced in the joints of the feet than in the hands. The rate of damage was independently associated with less disease activity, less frequent use of glucocorticoids, and with an improvement in aerobic fitness. CONCLUSION: The progression of radiological joint damage of the hands and feet in patients with RA is not increased by long term high intensity weightbearing exercises. These exercises may have a protective effect on the joints of the feet.

Differences between participants and nonparticipants in an exercise trial for adults with rheumatoid arthritis.

OBJECTIVE: To investigate the generalizability of the results of a randomized controlled trial on the effectiveness of long-term, high-intensity exercises in the rheumatoid arthritis patients in training (RAPIT) trial by comparing the characteristics of the participants with the nonparticipants. METHODS: Participants and nonparticipants were mailed questionnaires on sociodemographic characteristics, health status, reasons not to participate, and attitudes toward intensive exercise. RESULTS: The questionnaires from 892 (75%) nonparticipants and 299 (97%) participants were collected. The nonparticipants were slightly older, more often male, and had longer disease duration than the participants. The nonparticipants perceived their disease as more serious, used fewer disease-modifying antirheumatic drugs, had a lower level of education, and a more negative attitude toward intensive exercise. CONCLUSION: The results of the RAPIT trial might not be generalizable to the entire target population. To promote participation in long-term, high-intensity exercises, health professionals should more actively discuss the potential benefits of exercise with their RA patients while taking into consideration specific factors related to participation.

Lack of effect of doxycycline on disease activity and joint damage in patients with rheumatoid arthritis. A double blind, placebo controlled trial.

OBJECTIVE: To investigate the effects of doxycycline on disease activity and joint destruction in patients with rheumatoid arthritis (RA). METHODS: A 36 week double blind, placebo controlled crossover trial was conducted. Patients (n = 66) received 50 mg doxycycline or placebo twice a day during 12, 24, or 36 weeks. Patient assessments were performed before the treatment was administered, at 6, 12, 24 and 36 weeks of treatment, and finally at 4 weeks after cessation of treatment. Patient assessments, swollen and tender joint counts, duration of morning stiffness, erythrocyte sedimentation rate, and Modified Disease Activity Score were used as measures of disease activity. Effects on joint destruction were assessed by urinary excretion of the pyridinolines hydroxylysylpyridinoline and lysylpyridinoline and by scoring radiographic damage of hands and feet before and after treatment. RESULTS: The changes of clinical or laboratory disease activity measures, pyridinoline excretion, or progression of radiographic joint damage during doxycycline or placebo treatment did not differ significantly. CONCLUSION: The results indicate that 50 mg doxycycline twice a day provided no therapeutic benefit for patients with RA.

Catastrophic manifestation of the antiphospholipid syndrome.

We describe a young woman who displayed the "malignant" variant of the antiphospholipid syndrome (APS), also known as the "catastrophic APS." Renal insufficiency, retinopathy, cerebral infarcts, bone marrow necrosis, skin ulcers, and nasal septum perforation were the result of widespread thrombotic microangiopathy. She recovered during high intensity anticoagulation.