Spiritual healing as adjunct therapy for rheumatoid arthritis.

At the request of the Confederation of Healing Organizations (CHO) the addition of spiritual healing (SH) to conventional therapy has been compared with conventional therapy alone in 29 patients with rheumatoid arthritis (RA) using a parallel group design. Clinical and biochemical assessments were recorded at intervals while subjects received a 6-month course of spiritual healing. Initial psychological assessment was also performed. The addition of SH produced no significant improvement in any of the relevant clinical or laboratory parameters assessed; although groups were not exactly matched at the start, those requesting SH had more active disease. Between-group comparison showed only an improvement in summated change score (SCS) in favour of SH at week 16, which was lost by week 24. Individuals displaying the most improvement in pain score or SCS with SH did not have a significantly different psychological profile from those patients who showed the most deterioration. Although our study was small the results do not persuade us to proceed to a larger study for which there would be difficulties in study design.

The effect of sulphasalazine on neutrophil superoxide generation in rheumatoid arthritis.

The production of superoxide by the peripheral blood neutrophils of 19 patients with active rheumatoid arthritis was measured during treatment with sulphasalazine (SASP). The response to drug treatment was determined by change in plasma viscosity, CRP, early morning stiffness and articular index over a 10-point scale. Of the 19 patients studied, eight were considered to have responded well to SASP and seven to have responded poorly or not at all. Over the treatment period, plateau levels of superoxide production fell in seven of the eight responders (P = 0.028) compared with a non-significant fall in 3/7 of the non-responder groups. The initial rate of superoxide production also fell in the responder group, but this was not statistically significant. Initial values in both the responder and non-responder groups were comparable with those seen for normal controls. Analysis of drug levels showed all patients to be compliant with drug treatment; however, drug levels and neutrophil activity were not correlated. Studies of the effect of SASP and sulphapyridine on superoxide production in vitro showed no difference between good and poor responders. These results suggest that there is no inherent difference between good and poor responders regarding the susceptibility of their neutrophils to SASP. SASP's action on neutrophils, therefore, appears not to be its main mechanism of disease-modifying activity in RA.

A clinical and biochemical assessment of methotrexate in rheumatoid arthritis.

Low-dose methotrexate has gained widespread acceptance as a second-line agent in rheumatoid arthritis (RA). The Leeds Human Model Screening System (LHMSS) is a validated screening mechanism allowing the rapid evaluation of compounds for their potential as anti-rheumatic agents, the results of which have been confirmed in longer term studies. We have evaluated methotrexate in patients with RA using the LHMSS at a maintenance dose of 10mg/week. Significant change occurred in four out of eleven variables over a 24-week period (p < 0.01). This degree of change is greater than that seen with nonsteroidal anti-inflammatory agents but less than with other recognised second-line agents such as D-penicillamine, suggesting that methotrexate may have less potential as a second-line agent than D-penicillamine.

Optimizing the assessment of disease activity during treatment with anti-rheumatoid drugs.

Clinical trials in RA usually involve the use of several laboratory assessments of disease activity. Their use is not universal and the relative value of many novel assessments has not been determined in relation to existing clinical and laboratory methods. This study attempts to investigate the value of established and novel assessments of disease activity during treatment with accepted DMARDs. Over a 48-week study period, changes in cytidine deaminase (CD), beta 2-microglobulin, alpha 1-acid glycoprotein (alpha 1-AGP), serum antibodies to Clostridium perfringens alpha-toxin, pre-albumin and caeruloplasmin were compared to a group of established clinical and laboratory assessments including plasma viscosity, CRP haemoglobin and platelet count during treatment with the established second-line drugs, D-penicillamine (n = 20), sulphasalazine (n = 17), gold (n = 12) and hydroxychloroquine (n = 18). Overall, the assessments showing the greatest degree of change were plasma viscosity, articular index, summated change score, platelet count, CD, white cell count, alpha 1-AGP, CRP and pain score. The assessments showing the greatest degree of change were not homologous between the treatment groups and no single assessment was outstanding for a particular drug treatment.

Rheumatoid arthritis: effects on the family.

The impact of rheumatoid arthritis (RA) on the families of people with the disease is poorly understood. A qualitative study was undertaken on 22 patients with rheumatoid arthritis, their respective well partners and their 40 children. For most children the effect of living with a parent suffering from a painful, chronic illness was not detrimental, but a minority suffered verbal and physical abuse. The disease had wide-ranging effects on sexual and working relationships, but marriage to a partner with RA did not result in a threat to the relationship for the majority. Recommendations for future practice are made.

A clinical and biochemical assessment of a nonthiol ACE inhibitor (pentopril; CGS-13945) in active rheumatoid arthritis.

Captopril, which is a thiol containing angiotensin converting enzyme (ACE) inhibitor that has a close structural similarity to D-penicillamine, behaves as a disease modifying antirheumatic drug (DMARD) in rheumatoid arthritis (RA). In order to ascertain whether the DMARD-like properties of captopril reside in its ability to inhibit ACE or in the thiol group, we evaluated pentopril (CGS-13945) in patients with active RA. This recently synthesized drug is a nonthiol containing ACE inhibitor. Pentopril produced little clinical improvement and no biochemical improvement in a group of 15 patients with RA, many of whom were unable to tolerate it because of in-effect or side effects. A reduction in serum ACE activity and a modest fall in blood pressure suggested that the drug was exerting its pharmacological effect. Our study strengthens the argument that the therapeutic benefit of captopril in RA probably lies in its thiol group rather than in its enzyme inhibition properties, and that the thiol group may be the effective moiety in some other DMARD.

A comparison of choline magnesium trisalicylate and acetylsalicylic acid in patients with rheumatoid arthritis.

Choline magnesium trisalicylate (3.0 g/day) and enteric-coated acetylsalicylic acid (3.0 g/day) have been compared in a double-blind, crossover study on 19 patients with rheumatoid arthritis using the double-dummy technique. Patients were allocated to receive 3-weeks' treatment with each trial drug in random sequence and were assessed at Weeks-1, 0, 3 and 6. Apart from an unexplained significant improvement in grip strength (p less than 0.01) that occurred in patients on choline magnesium trisalicylate when this followed aspirin but not when it preceded it, there was no significant clinical difference between treatments in any of the clinical parameters of improvement that were measured. There was also no clear difference in the side-effects profile produced by the two drugs, but the number of patients recruited to this study was small.

A multiple dose pharmacokinetic and tolerance study of once daily 200 mg sustained-release flurbiprofen capsules in young and very elderly patients.

The pharmacokinetic profile of 200 mg sustained-release flurbiprofen capsules was compared in nine elderly (mean age 84.2 years) and 10 young (mean age 38.1 years) patients with arthritis. After a single capsule, a 48 h plasma concentration profile was performed. The patients then took 1 capsule daily for a further 13 days with plasma levels of the drug being measured pre-dose on alternate days. Following ingestion of the last capsule, a further 48 hour plasma concentration profile was performed. These results were compared with each other and with computer predicted data obtained from dosing with 200 mg conventional flurbiprofen (as 100 mg b.d.). In both young and elderly patients, the two 48 h plasma concentration profiles confirmed the sustained-release characteristics of the capsule. There was no evidence of dose-dumping, although, in one elderly patient with a partial gastrectomy, higher plasma concentrations were observed. Inter- and intra-patient variability was acceptable. A steady-state was achieved within the predicted four days in both groups and there was no evidence of accumulation with the daily dosing interval. A mean steady-state level of approximately 6 micrograms/ml was achieved for both populations. Computer predicted data for 200 mg conventional flurbiprofen (as 100 mg b.d.) showed a pre-dose/peak range of 1-12 micrograms/ml. The pre-dose/peak ranges for the young and old patients were 4-10 micrograms/ml and 4-8 micrograms/ml respectively. One young patient developed a hypersensitivity reaction of moderate severity; one young and four elderly patients developed a low haemoglobin concentration during the study. No other changes in haematological or biochemical parameters were seen.

A double-blind comparison of ibuprofen, placebo and ibuprofen with meptazinol in soft tissue rheumatism.

The administration of ibuprofen potentiates and prolongs the analgesic effect of meptazinol when the two drugs are given simultaneously to mice. A double-blind three-way crossover study of placebo, ibuprofen (1600 mg/day) and ibuprofen (1600 mg/day) plus meptazinol (400 mg/day) was carried out in 45 patients with soft tissue rheumatism to see if the same potentiation could be demonstrated in man. Treatment order was randomized and each regimen was given for 2 weeks preceded by 1 week on paracetamol alone. Assessments were made, on entry and after each treatment period, of pain parameters using visual analogue or verbal rating scales. Patients' overall impression and final preference showed both active treatments to be better than placebo and demonstrated a slight preference for the combination.

A study to determine the active moiety of sulphasalazine in rheumatoid arthritis.

Thirty patients with active rheumatoid arthritis (RA) participated in an open study of 6 months' treatment with either 5-aminosalicylic acid (5-ASA) or sulphapyridine (SP), the two moieties of sulphasalazine (SASP). Patients were assessed at regular intervals using clinical and biochemical tests designed to detect specific antirheumatic activity. Patients taking SP showed significant improvement in disease activity, but those taking 5-ASA did not improve, despite the fact that high serum concentrations of 5-ASA and acetyl 5-ASA were achieved. These results suggest that SP is the active moiety of SASP. Its possible mode of action is discussed. Nausea was a frequent problem in patients taking SP. Unless this can be overcome, SP is unlikely to offer any therapeutic advantages over SASP in the treatment of RA.

A parallel group comparison of tenoxicam and piroxicam in patients with ankylosing spondylitis.

Tenoxicam (20 mg/day) and piroxicam (20 mg/day) were compared in a double-blind, parallel group study over 4 weeks in 30 patients with ankylosing spondylitis. Both tenoxicam and piroxicam reduced spinal pain, but the improvement was greater with piroxicam. Tenoxicam and piroxicam were equally effective at improving duration of morning stiffness. Slight improvement was seen with other symptoms with both treatments. Patients were slightly more tolerant of piroxicam than tenoxicam and most patients elected to continue on their particular therapy at the end of the study.

5-Aminosalicylic acid or sulphapyridine. Which is the active moiety of sulphasalazine in rheumatoid arthritis?

Thirty patients with active rheumatoid arthritis participated in an open study of 6 months' treatment with either 5-aminosalicylic acid or sulphapyridine, the two moieties of sulphasalazine. Patients were assessed at regular intervals using a number of clinical and biochemical tests designed to detect specific antirheumatic activity. Patients taking sulphasalazine showed significant improvement in most parameters of disease activity, but those taking 5-aminosalicylic acid did not improve despite the fact that high serum concentrations of 5-aminosalicylic acid and acetyl 5-aminosalicylic acid were achieved. These results suggest that sulphapyridine is the active moiety of sulphasalazine. Its possible mode of action is discussed. Nausea was a frequent problem in patients taking sulphapyridine. Unless this problem can be overcome, sulphapyridine is unlikely to offer any therapeutic advantages over sulphasalazine in the treatment of rheumatoid arthritis.

Single and multiple oral dose pharmacokinetics of tenoxicam in the elderly.

Tenoxicam is a new non-steroidal anti-inflammatory drug with a long half-life. Since such drugs may be particularly prone to accumulate in elderly patients, a group of the population in which anti-inflammatory agents are most commonly prescribed, we have studied the pharmacokinetics of tenoxicam in 18 patients (age range 62-87 years) with osteoarthrosis or rheumatoid arthritis. A pharmacokinetic profile was performed after a single 20 mg oral dose. Patients then took regular medication until they had reached steady-state for chronic dosing (20 mg/day) when a further pharmacokinetic profile was performed. Approximately five-fold accumulation was found at steady-state (mean peak plasma level 2.6 micrograms/ml for a single dose against 12.4 micrograms/ml at steady-state). Twenty percent of the dose was eliminated in the first dose interval. Mean pre-dose plasma level at steady-state was 9.6 micrograms/ml with a coefficient of variation of 11%. Serial haematological and biochemical estimations during the study showed no evidence of drug toxicity.