Additive effect of combined naproxen and paracetamol in rheumatoid arthritis. Non-steroidal anti-inflammatory drugs as the first step in cancer pain therapy: double-blind, within-patient study comparing nine drugs. Bumadizone calcium in the treatment of rheumatoid arthritis. [Clinical study on a new acetylsalicylic acid/paracetamol preparation with gastric acid resistant coating (Safapryn), and on two various phenylbutazone dosages in patients with primary chronic polyarthritis as based on a new evaluation method]. Patient Preference for Placebo, Acetaminophen (paracetamol) or Celecoxib Efficacy Studies (PACES): two randomised, double blind, placebo controlled, crossover clinical trials in patients with knee or hip osteoarthritis. Evaluation of information given to rheumatology patients using non-steroidal anti-inflammatory drugs. Endocrine control of inflammation: rheumatoid arthritis double-blind, crossover clinical trial. [A double blind trial of alfacalcidol on patients with rheumatoid arthritis (RA)]. Nonsteroidal anti-inflammatory drugs and the incidence of Parkinson disease.
The clinical effect and plasma naproxen levels were studied in 20 patients with RA receiving three doses of naproxen and two naproxen doses combined with paracetamol (acetaminophen) in a randomized, double-blind, comparison in five 2-wk treatment periods. A significant dose-concentration effect relationship was found for the three naproxen doses (500, 1000 and 1500 mg daily). The following variables were measured: global clinical effect, joint index, morning stiffness, activity of daily living (ADL), pain during movement and at rest. The naproxen dose-concentration effect relationship curve was moved to the left by the addition of 4 g paracetamol daily. No major side effects were observed, but complaints concerning the gastrointestinal tract were fewer on lower naproxen doses and these were not increased by concomitant paracetamol treatment. The results show that the clinical effect of naproxen in RA may be significantly increased by concomitant paracetamol administration. The efficacy and tolerability of acetylsalicylic acid, paracetamol, diclofenac, ibuprofen, indomethacin, pirprofen, sulindac, naproxen and suprofen were compared in the treatment of cancer pain. In a double-blind, within-patient randomized study, each drug was given for 1 week to eight patients and for another week to a further eight patients. A total of 65 patients were effectively treated; only 48 completed week 1 and 41 completed week 2. Naproxen, diclofenac and indomethacin were highly effective in pain relief (tested by means of a 100 mm visual analogue scale) and were relatively well tolerated. It is concluded that these non-steroidal anti-inflammatory drugs can be considered as first choice in the treatment of cancer pain. A double-blind crossover trial of bumadizone calcium (Eumotol), a non-steroidal anti-inflammatory drug, has been carried out in 56 patients with rheumatoid arthritis. On both objective and subjective criteria bumadizone was superior to placebo and paracetamol at a statistically highly significant level (P less than 0,01). When tested against acetylsalicylic acid, bumadizone was more effective in 13 patients and less effective in 4 patients. Although this does not represent a statistically significant difference it does suggest that its anti-inflammatory and analgesic qualities are at least equal to those of salicylate in high dosages. There were no serious side-effects in the patients who received bumadizone and the drug was better tolerated than either acetylsalicylic acid or paracetamol. The authors describe a simple non-crossover-blind test for the evaluation of subjective indices. A table for recording pains during the 14 days' study is described. The patient's satisfaction with the treatment and the number of days until withdrawal from the trial are recorded. The statistical procedure takes into consideration differences between the treatment groups and makes possible a valuable comparison with drugs tested in other clinical trials. The three dose schedules of antirheumatic treatment were tested on 122 patients and the results compared with those of 342 patients treated with the 6 other antirheumatic drugs (enteric-coated aspirin, paracetamol, indomethacin, flurbiprofen, mefenamic acid, and prednisolone) and those of 41 patients who received placebos. The results show that Safapryn (3,6 g aspirin + 3.0 g paracetamol daily) compared with 3.9 g enteric coated aspirin does not offer any advantage in its analgesic effect, although it gives rise to fewer side effects. Phenylbutazone (3000 mg) was almost as effective as 15 mg prednisolone daily. Between the effects of this dosage of phenylbutazone and other non-steroidal antirheumatic drugs, however, no significant difference could be detected. 50 mg phenylbutazone daily and placebo treatment could not be distinguished. The authors thank the Arthritis and Rheumatism Council for Research in Great Britain for its financial support. One of the authors (PL) was a Merck, Sharp, and Dohme Research Fellow and another one (PMB) received a Robins research scholarship. Acetaminophen (paracetamol) is recommended as the initial pharmacological treatment for knee or hip osteoarthritis. However, survey and clinical trial data indicate greater efficacy for non-steroidal anti-inflammatory drugs and cyclo-oxygenase-2 specific inhibitors.
                Two randomised, double blind, placebo controlled, crossover multicentre clinical trials, Patient Preference for Placebo, Acetaminophen or Celecoxib Efficacy Studies (PACES).Patients: Osteoarthritis of knee or hip.Intervention: "Wash out" of treatment; randomisation; 6 weeks of celecoxib 200 mg/day, acetaminophen 1000 mg four times a day, or placebo; second "wash out;" crossover to 6 weeks of second treatment.Measurements: Western Ontario McMaster Osteoarthritis Index (WOMAC), visual analogue pain scale, patient preference between two treatments.
                Celecoxib was more efficacious than acetaminophen in both periods in both studies; WOMAC and pain scale scores differed at p<0.05 in period II and both periods combined of PACES-a and in periods I and II and both periods combined in PACES-b, but not in period I of PACES-a. Acetaminophen was more efficacious than placebo, generally p<0.05 in PACES-b, and >0.05 in PACES-a. Patient preferences were 53% celecoxib v 24% acetaminophen in PACES-a (p<0.001) and 50% v 32% in PACES-b (p = 0.009); 37% acetaminophen v 28% placebo in PACES-a (p = 0.340) and 48% v 24% in PACES-b (p = 0.007). No clinically or statistically significant differences were seen in adverse events or tolerability among the three treatment groups.
                Greater efficacy was seen for celecoxib v acetaminophen v placebo, while adverse events and tolerability were similar. Variation in results and statistical significance in the two different trials are of interest. This paper reports the findings of a study of information given to rheumatology patients using non-steroidal anti-inflammatory drugs. One hundred and twenty patients were randomized to three groups. Group A received an information leaflet, Group B received both a leaflet and a verbal explanation and Group C received only a verbal explanation. Information was gathered on demography, knowledge base, sources of information, satisfaction with the leaflet and further information requirements. Data were collected by questionnaires which were completed before randomization and 8-12 weeks later. Analysis indicates the potential benefits of giving information to patients although the full implications of these benefits are not clear and further research is indicated in this important area. A dysfunction in the endocrine control system for inflammation in rheumatoid arthritis serves as the theoretical basis for chronic inflammation in the study design described. Eighteen patients with rheumatoid arthritis, who acted as their own controls, were brought to a minimum symptom state through conventional means, trained, and allowed to control subsequent flares by a patient-initiated, flare-response prednisone regimen. The six-month trial was double-blind with a crossover at midpoint. While continuing stable non-steroidal anti-inflammatory and disease modifying antirheumatic drug therapies, the patients averaged additional 57% and 75% reductions from baseline in tender joint count and total pain score, respectively, on the prednisone therapy. The prednisone therapy was differentiated by improvement from that of a placebo by six of the nine parameters evaluated. The adverse events were no more frequent with prednisone than with placebo use. The efficacy of prednisone was increased threefold while reducing consumption by 40% when compared to the predecessor 5-mg prednisone/day clinical trial. A double blind comparative trial was performed in order to study the efficacy and safety of alfacalcidol (1 alpha-OH-D3) in a total of 140 patients with RA admitted to 31 institutes, using a placebo as the control. The treatment period was 16 weeks. The doses of 1 alpha-OH-D3 were 1.0 microgram/day and 2.0 micrograms/day. It was permissible to use non-steroid anti-inflammatory drugs for basic treatment and oral steroidal preparations for maintenance treatment without changing the doses of these drugs during the study period in patients who had been treated with them before participating in the study (for oral steroidal preparations, the dose was limited to 5 mg/day or less as prednisolone). The percentage of patients with slight improvement was about 10% higher in 1 alpha-OH-D3 groups than in placebo group, but the difference between them was not significant. The results tended to be better in the treated groups than in the placebo group, but there was no significant difference between them with regard to duration of morning stiffness, number of joints with pain, number of joints with swelling and Lansbury's index. The effects of 1 alpha-OH-D3 on various immunological parameters including lymphocyte subsets were not clearly demonstrated. However, interestingly, the ratio of OKT-4/OKT-8 was found not to change in patients whose initial value was normal, while it tended to decrease after 1 alpha-OH-D3 treatment in patients whose initial value was abnormally high. The improvement of bone atrophy was judged by microdensitometry (MD) method using X-ray picture of hands. The indexes of bone density (GS max, GS min and sigma GS/D) demonstrated that 1 alpha-OH-D3 prevents reduction in bone density. 1 alpha-OH-D3 did not trigger hypercalcemia in any case. However there was a slight but significant increase of serum Ca value in the group with higher dose (2.0 micrograms/day). Taking the efficacy into consideration, the dose of 1.0 microgram/day was judged to be suitable for long-term treatment. Animal and epidemiologic studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the incidence of Parkinson disease (PD). The authors studied 1,258 PD cases and 6,638 controls from the General Practice Research Database. The odds ratios (95% CI) for ever vs never use were 0.93 (0.80 to 1.08) for nonaspirin NSAIDs, 1.29 (1.05 to 1.58) for aspirin, and 1.16 (1.00 to 1.35) for acetaminophen. Nonaspirin NSAID use was associated with a higher risk in women and a lower risk in men.
When considering the trade off between the benefits and harms of non-steroidal anti-inflammatory drugs and paracetamol/acetaminophen, it is not known whether one is better than the other for rheumatoid arthritis. But people with rheumatoid arthritis and the researchers in the study did prefer non-steroidal anti-inflammatory drugs more than acetaminophen/paracetamol. There is a need for a large trial, with appropriate randomisation, double-blinding, test of the success of the blinding, and with explicit methods to measure and analyse pain and adverse effects.