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Biomedical subjects

P S Hanrahan

Publications and source records attributed to P S Hanrahan.

7 recordsLinked to original sources

A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate.

OBJECTIVE: To assess the efficacy and safety of 100 mg daily anakinra (Kineret), a recombinant form of the naturally occurring interleukin 1 receptor antagonist, plus methotrexate (MTX) in reducing the signs and symptoms of rheumatoid arthritis (RA). METHODS: Patients with active RA (n = 506) despite current treatment with MTX were enrolled in this multicentre, double blind, randomised, placebo controlled study. Patients received subcutaneous injections of anakinra 100 mg/day or placebo. They were assessed monthly for 6 months for improvement in signs and symptoms of RA and for adverse events. The primary efficacy measure was the percentage of patients attaining ACR20 response at week 24. RESULTS: Significantly greater proportions of patients treated with anakinra compared with placebo achieved ACR20 (38% v 22%; p<0.001), ACR50 (17% v 8%; p<0.01), and ACR70 (6% v 2%; p<0.05) responses. The response to anakinra was rapid; the proportion of patients with an ACR20 response at the first study assessment (4 weeks) was twice as high with anakinra as with placebo (p<0.005). Clinically meaningful and statistically significant responses were also seen in individual components of the ACR response (for example, Health Assessment Questionnaire, pain, C reactive protein levels, and erythrocyte sedimentation rate). Anakinra was well tolerated, with a safety profile, similar to that of placebo with one exception: mild to moderate injection site reactions were more common with anakinra than with placebo (65% v 24%). CONCLUSIONS: This study confirms previous observations from a dose-ranging study showing that anakinra, in combination with MTX, is an effective and safe treatment for patients with RA who have inadequate responses to MTX alone.

Antirheumatic Agents↗

Prospective long term follow-up of methotrexate therapy in rheumatoid arthritis: toxicity, efficacy and radiological progression.

We followed all 128 patients started on methotrexate (MTX) for rheumatoid arthritis (RA) over a 4-year period. Forty-nine were followed for over 3 years. Forty-three patients discontinued treatment, 23 because of toxicity, 15 for inefficacy and five for other reasons. Forty-seven of the 75 followed on treatment for over 2 years had hand radiographs available before and after this treatment period. None showed improvement and 15 showed marked deterioration. Patients' acceptance of this therapy was good although most were noted objectively to have persistent disease activity. We would recommend that if MTX is to be used, a more aggressive approach be adopted to reduce not only the symptoms but the signs of active disease.

Aged↗

Concurrent use of folinic acid and methotrexate in rheumatoid arthritis.

In a double blind placebo controlled crossover study, each arm of 4 weeks' duration, 20 mg of folinic acid/week or placebo were administered to 13 patients with rheumatoid arthritis. These individuals were receiving weekly intramuscular methotrexate (MTX) but were about to discontinue because of side effects. While there was considerable improvement in nausea during the study, the effect of folinic acid could not be differentiated from that of placebo. There was no adverse effect on control of disease activity. It therefore seems likely that polyglutamated tissue stores of MTX do not contribute to drug efficacy and in this format folinic acid could not be shown to be more useful than placebo in reducing drug induced nausea.

Adult↗

Ankylosing spondylitis and multiple sclerosis: an apparent association?

The prevalence of HLA-B27 in 420 patients with multiple sclerosis (MS) was 43 (10.2%). Five of 20 B27 positive patients who were further assessed clinically and radiologically had ankylosing spondylitis (AS), a prevalence of between 12 and 25%, compared with previously established prevalence rates of B27 in members of the normal population of between 1 and 2% Sixteen patients with AS underwent brainstem auditory (BAEP), visual (VEP) and somatosensory (SSEP) evoked potential studies, with only minor, and predominantly peripheral, abnormalities of SSEP, except for one patient who developed MS during the study. Our data lend some support to an association between AS and MS but refute the possibility of a frequent subclinical MS-like syndrome in AS. They show there is unlikely to be any confusion when performing evoked potential studies in patients with AS.

Adult↗