Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components.

OBJECTIVES: To investigate the potential clinical benefit of a combination therapy. METHODS: 205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying antirheumatoid drugs previously, with an early (< or = 1 year duration), active (Disease Activity Score (DAS) > 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68). RESULTS: The mean changes in the DAS during the one year follow up of the study was -1.15, -0.87, -1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007). CONCLUSION: This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable.

[Manifestation of neuro-Behçet disease in cyclosporin A therapy]. / Manifestation eines Neuro-Behçet unter Cyclosporin A-Therapie.

Behçet's disease is a chronic inflammatory disorder characterized by the triad of oral and genital ulcers and ocular lesions. One of the most life-threatening manifestations results from involvement of the central nervous system, presenting as necrotising meningo-encephalitis, most typically affecting the brain stem, internal capsula and basal brain ganglia. We report on a young Caucasian mate with Behçet's disease (HLA B 51+) and recurrent uveitis, who presented with acute neurologic involvement under CyA therapy 5 years after first diagnosis. At the time of admission MRI showed two high intensity lesions in the brain stem on T1 weighted images enhanced with Gd-DTPA, reflecting active inflammation. Shortly after admission the CyA treatment was stopped and a therapy with high dose steroids and chlorambucil, starting with a dose of 2 mg daily was initiated. This led to improvement of neurologic symptoms, also documented by brain stem evoked potentials and investigations of cerebrospinal fluid, as well as of ophtalmologic symptoms within few days of treatment. Steroids were reduced to a maintenance dose of 12 mg Prednyliden daily. The brain MRI taken 8 weeks after onset of chlorambucil treatment showed the same lesions in the brain stem, with low intensity in the T1 weighted images an no longer enhanced Gd-DTPA uptake. Chlorambucil dose was reduced to 2 mg every second day after 8 months. There was no exacerbation in the follow-up of 12 months. We conclude that a 6-week Chlorambucil therapy consisting of 2 mg/p.o./d led to remission of neurologic involvement firstly evolving under CyA-medication which suggests superiority of chlorambucil as a treatment modality in neurologic as well as ophtalmologic features of the disease.

99m-Tc-HMPAO-SPECT in diagnosis of early cerebral vasculitis.

The objective of this study was to evaluate whether mild neurological symptoms suggestive of neuropsychiatric involvement may be associated with cerebral perfusion defects as detected by functional brain imaging with 99m-Tc-HMPAO-SPECT (single photon emission computed tomography). SPECT analysis for the early detection of central nervous system (CNS) involvement was evaluated in 40 consecutive patients with systemic vasculitis or with Sneddon's syndrome. Of these, 18 patients showed overt neuropsychiatric symptoms, so-called major symptoms (e.g. motoric or sensible defects); 6 had mild symptoms like headache or cognitive disorders, so-called minor symptoms: 16 patients did not present with any of these symptoms. SPECT abnormalities were detected in 16 of the 18 patients with overt neuropsychiatric symptoms (89%). Five of the 6 patients with minor symptoms (83%) and 5 of the 16 patients without neurological symptoms (31%) also had SPECT abnormalities. There was no relation to disease activity or duration. We concluded that the high sensitivity of SPECT (87.5%) in detecting perfusion abnormalities among the evaluated group of patients indicates its suitability for early diagnosis of vasculitic CNS involvement.