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Biomedical subjects

T Pullar

Publications and source records attributed to T Pullar.

At least 73 records · Page 4Linked to original sources
PubMed1987

Effect of sulphasalazine on the radiological progression of rheumatoid arthritis.

We have investigated the influence of sulphasalazine, a second line antirheumatic drug, on the radiological progression of erosions in rheumatoid arthritis over a two year period in 41 patients. Hand radiograph scores deteriorated significantly over this period, but in a group of 31 patients in whom one year films were also available this deterioration was limited to the first year. This slowing of radiological deterioration was not related to 'normalisation' of the erythrocyte sedimentation rate (ESR). Compared with a 'control' group of 10 patients who had refused offers of second line therapy, sulphasalazine treated patients showed less deterioration over the two year period, and this difference was more marked than in previous studies of gold or penicillamine. No significant change was seen in large joint radiographs in sulphasalazine treated patients over two years, but this probably represents the poor sensitivity of the method of assessment. No significant correlation was seen between changes in inflammatory indices and slowing of radiological deterioration in erosion score. Thus sulphasalazine appears to slow the progression of radiological disease of the hands over the second year of treatment in a representative sample of patients who continue to receive treatment for two years.

Arthritis, Rheumatoid↗
PubMed1987

General practitioner assistance with gold and penicillamine therapy of rheumatoid arthritis--a four year prospective study.

One hundred patients with active rheumatoid arthritis, uncontrolled by symptom relieving agents, were allocated randomly to intramuscular gold or oral penicillamine therapy. Their general practitioners (97 in all) were requested to assist with blood, urine, skin and mucous membrane monitoring. After four years, 16 patients in each treatment group remained on their original therapy, and three-quarters of these continued attending their family doctor for toxicity monitoring. Most GP monitoring problems occurred in the first six months of treatment. Sustained improvement in haemoglobin and ESR was seen in both treatment groups. Second-line drug toxicity monitoring by general practitioners allows specialist time to be diverted to rheumatological problem solving but may make it more difficult to relate rare but serious adverse adverse events to drug therapy.

Arthritis, Rheumatoid↗
PubMed1986

Sulphasalazine for rheumatoid arthritis: toxicity in 774 patients monitored for one to 11 years.

Sulphasalazine is being used increasingly to treat rheumatoid arthritis, though its long term safety profile has not been established in this condition. The incidence and nature of adverse effects occurring in 774 patients with rheumatoid arthritis treated with sulphasalazine for periods ranging from one to 11 years were therefore noted. Altogether 205 of the patients stopped treatment permanently due to an adverse effect. One hundred and fifty six (76%) of these events occurred within three months and few beyond the first year. Most events were trivial and were self limiting after withdrawal of the drug; of the potentially more serious adverse effects, 33 (66%) occurred within three months of treatment. None of the patients died or suffered lasting ill effects. It is concluded that adverse effects of treatment with sulphasalazine are generally seen within three months; though regular monitoring is desirable during that period, thereafter few worrying problems occur.

Adolescent↗
PubMed1986

Selection of suitable patients for second-line therapy in rheumatoid arthritis.

Investigators studying second-line drugs often try to enroll 'ideal' patients with a high ESR, short disease duration and who have received no previous second-line therapy. In this paper we investigate the influence of gender, disease duration, previous second-line therapy, and initial ESR in 150 rheumatoid patients with clinically-active disease treated with sulphasalazine. Clinical improvement was seen in all subgroups and no difference in toxicity could be demonstrated. Haematological response was absent in patients with an initial low ESR although these patients improved clinically. Thus, patients with clinically-active disease suggesting a need for second-line drugs should benefit from sulphasalazine therapy irrespective of any of the above variables. The implications for clinical trial design regarding patients with low ESR, however, may be more complex.

Arthritis, Rheumatoid↗
PubMed1986

Comparison of white blood cell dyscrasias during sulphasalazine therapy of rheumatoid arthritis and inflammatory bowel disease.

A total of 7 out of 158 rheumatoid arthritis patients followed for 6 months have developed leucopenia during sulphasalazine therapy at our centre. Two of these patients developed profound leucopenia which necessitated admission to a laminar flow unit, and case reports of these are documented in detail. These results are compared with those from other centres in the United Kingdom where patients with rheumatoid arthritis have been treated, and also with experience gained from patients with inflammatory bowel disease who have been treated with sulphasalazine.

Aged↗
PubMed1986

Variables affecting efficacy and toxicity of sulphasalazine in rheumatoid arthritis. A review.

Studies of sulphasalazine in rheumatoid arthritis have used largely empirical doses. The available literature suggests that the optimum dose appears to be greater than 40 mg/kg/day. Despite the relationship between dose and efficacy and a good correlation between dose and serum concentrations of sulphasalazine and its metabolites, no relationship has been demonstrated between efficacy and serum concentrations of sulphasalazine or its metabolites, although there is some suggestion that higher concentrations on single dosing are achieved in patients who develop upper gastrointestinal symptoms. Furthermore, acetylator phenotype does not affect efficacy, although upper gastrointestinal symptoms are more common in slow acetylators.

Acetylation↗
PubMed1985

Which component of sulphasalazine is active in rheumatoid arthritis?

Sulphasalazine is known to be effective as a second line agent in the treatment of rheumatoid arthritis. The two chemical constituents of sulphasalazine (sulphapyridine and 5-aminosalicylic acid) were assessed separately in the treatment of rheumatoid arthritis. Over 24 weeks sulphapyridine showed a pronounced second line effect comparable with sulphasalazine and with a similar toxicity profile, whereas 5-aminosalicylic acid showed only a weak first line effect. Thus sulphapyridine appears to be the active moiety responsible for the second line effect of sulphasalazine in rheumatoid arthritis. The efficacy of the antibacterial component of sulphasalazine yet again permits speculation about the role of a bacterial pathogen in the aetiopathogenesis of rheumatoid disease.

Adult↗
PubMed1985

Second line therapy in rheumatoid arthritis--a four year prospective study.

One hundred and twenty-three rheumatoid patients were commenced on one of the three second-line agents: sodium aurothiomalate (GST), penicillamine (P), or levamisole (L). After four years, 39% of the GST group, 20% of the penicillamine group, and 8% of the levamisole group remained on the original agent. Fifty five % of patients, however, were receiving some second-line agent at four years, and patients showed an improvement in inflammatory indices irrespective of whether or not they were still receiving second-line therapy. It is unclear whether this improvement reflects the natural history of the disease, or the fact that regular clinic attendance identifies patients who require further second-line therapy following cessation of the initial agent.

Adult↗
PubMed1985

Sulphasalazine in the treatment of rheumatoid arthritis: relationship of dose and serum levels to efficacy.

Previous studies of sulphasalazine in rheumatoid arthritis have chosen an empirical dose based upon its use in ulcerative colitis. In this study we compare the efficacy and toxicity of two doses (1.5 g/day and 3 g/day, 30 patients per group), and attempt to relate efficacy to serum levels of sulphasalazine and its metabolites. After six months 24 of the low-dose group and 20 of the high-dose group remained on treatment. Greater improvement was seen in the high-dose group. When dose was expressed as mg/kg, the dose efficacy ratio became more apparent and a dose of greater than 40 mg/kg/day appears to confer greater benefit. No relationship was demonstrated between serum levels of sulphasalazine or its measured metabolites, and efficacy. We conclude that response to sulphasalazine in rheumatoid arthritis is dose dependent but does not relate to serum levels of sulphasalazine, sulphapyridine, or acetyl sulphapyridine.

Adult↗
PubMed1985

Effect of acetylator phenotype on efficacy and toxicity of sulphasalazine in rheumatoid arthritis.

A group of 54 patients with rheumatoid arthritis (31 fast, 23 slow acetylators) treated with sulphasalazine 3 g/day were studied retrospectively. At 24 weeks no difference in the efficacy of the drug could be shown between fast and slow acetylators. In a second prospective study 40 fast acetylators were allocated to 3 g/day and 20 slow acetylators to 1.5 g/day. At 24 weeks marked improvement was seen in the fast acetylators given high dose but not the slow acetylators given low dose. It was also noted in this study that the usual ratio of fast : slow acetylators was reversed, and there is some suggestion that fast acetylators may be predisposed to more severe rheumatoid arthritis. The toxicity pattern in a total of 149 patients (83 fast, 66 slow acetylators) was also studied. Significantly more slow acetylators stopped treatment because of nausea or vomiting, or both, but serious toxicity was not confined to either group. Acetylator phenotype therefore appears important in determining the incidence of nausea and/or vomiting associated with sulphasalazine therapy in patients with rheumatoid arthritis but has no effect on the occurrence of potentially serious toxicity or efficacy. Thus prior measurement of acetylator phenotype in patients with rheumatoid arthritis confers little practical benefit in their management.

Acetylation↗
PubMed1985

A rheumatological dilemma: is it possible to modify the course of rheumatoid arthritis? Can we answer the question?

The question 'Does the use of second-line therapy confer long-term benefit on outcome measures in rheumatoid arthritis?' remains unanswered. The major obstacle which prevents collection of the necessary data is the lack of a suitable control group. In this report experience with three 'second-line placebo groups' is described, and previous studies in the literature which incorporated a placebo group are reviewed. In the absence of concurrent corticosteroid therapy very few patients remain on placebo second-line medication after one year. Those that do, appear to have milder disease and are not representative of the group as a whole. Data on outcome measures need to be collected over two to five years, but the answer to the question which is posed does not depend upon larger and larger placebo groups which constitute increasing bias. To define the extent of benefit offered by the more powerful therapeutic agents a novel approach in regard to drug assessment will be required.

Anti-Inflammatory Agents↗
PubMed1985

Chrysotherapy and thrombocytopenia.

In a study of the clinical and immunogenetic profiles of 17 patients with rheumatoid arthritis and thrombocytopenia (platelet count less than 150 000/mm3 (150 x 10(9)/l)) due to gold therapy two clinical patterns were distinguished without knowledge of HLA type: group I, an early precipitous thrombocytopenia (10 patients), and group II, a less dramatic fluctuant fall (seven patients). In group I patients the clinical and laboratory features suggested an immune mediated, peripheral destruction of platelets, and all patients in this group were found to be HLA-DR3 positive. Two patients subsequently received penicillamine without toxicity. In group II the basis of thrombocytopenia appeared to be different, and only two patients in this group were HLA-DR3 positive. All group II patients had received penicillamine; four developed a thrombocytopenia. Mechanisms of toxicity in both groups are discussed. It would appear that HLA typing in unlikely to help in predicting all those patients at risk of toxicity during chrysotherapy.

Arthritis, Rheumatoid↗
PubMed1985

Have the newer NSAIDS contributed to the management of rheumatoid arthritis?

Approximately 30 non-steroidal anti-inflammatory agents are available for the treatment of rheumatoid arthritis. In this study patient acceptability of five such agents (benoxaprofen, fenbufen, feprazone, flurbiprofen, ketoprofen) is compared in groups of 50 patients with rheumatoid arthritis. Less than 40 per cent of patients continued on the prescribed drug for six months. Significantly more patients stopped fenbufen than stopped feprazone, otherwise dropout rates between the groups were similar. The overall efficacy and toxicity of most currently prescribed NSAIDs appear to be similar, and the availability of a surfeit of such agents dilutes clinical experience with any one drug. Despite subsequent events this method failed to differentiate benoxaprofen from the other agents. It would seem likely that this surfeit of similar drugs hinders detection of unusual complications, and impedes satisfactory management of inflammatory rheumatic disorders.

Anti-Inflammatory Agents↗