In single-dose parenteral studies with mice and dogs, the methyl ester hydrochloride of amphotericin B proved to be significantly less toxic than the parent compound, especially to the kidney.

In the long-term application, MTX was the most efficient compound, followed by AZA, whereas CQ had the poorest drug survival. Our results underline the value of long-term observations under the conditions of clinical practice as a supplement to controlled clinical trials.

Despite ample evidence in the literature that cathepsin activity contributes to the pathogenesis of inflammatory joint disease, this is not reflected by the conditions in peripheral blood. In contrast to the cysteine proteinases, MMP-1 and MMP-3 as well as MT complex are elevated in RA. In the context of findings in the literature, this stresses the importance of MMP as disease activity markers, compared to cysteine proteinases or their inhibitors.

The efficacy and safety of a combination of methotrexate (MTX), chloroquine (CQ) and cyclophosphamide (CYC) were studied in patients with refractory rheumatoid arthritis. A single-centre, matched-pair observational study with prospectively gathered data was performed. Fifty-six patients who had previously failed with MTX were treated with 15 mg MTX per week, 50 mg CYC three times a week and 250 mg CQ per day (group A). A 50% improvement of the swollen joint count was required to continue therapy. Data were compared with the results of the previous MTX therapy in the same group and with a matched-patient cohort receiving MTX monotherapy for the first time (group B). In group A, the combination therapy resulted in a significant decline of the swollen joint count after 1 year, in contrast to the previous MTX monotherapy in the same group. Complete remission of joint swelling was achieved in 13 patients (23%), compared with 26 patients in group B (47%). The median duration of effective combination treatment in group A was significantly longer than preceding therapies with MTX alone (19 vs 13 months, p<0.05). However, patients in group B could be treated for a median of 57.5 months (p<0.0001 compared with group A). Side-effects were comparable in both groups. The applied DMARD combination is safe and beneficial in a significant proportion of patients if MTX monotherapy is ineffective.

Although cyclophosphamide (CYC) is an effective drug in the treatment of refractory rheumatoid arthritis (RA), the application of this drug in RA has largely been abandoned, due to potentially life-threatening adverse events such as myelosuppression and cancer development. However, the question remains open, whether it is possible to balance the toxicity and the efficacy of CYC with low-dose therapy. 108 patients with refractory RA or with vasculitic organ involvement were treated with 50 mg CYC per day. Joint indices and laboratory parameters were gathered prospectively and the occurrence of serious side effects was monitored over a median of 10 years. The efficacy was surveyed in six months intervals. A 50% improvement of the swollen joint count was required to continue therapy. A long-term follow-up was performed to survey the incidence of malignancies. 85 patients dropped out within the first year. Only four patients were treated for longer than 4 years. In the total cohort, 50 patients were withdrawn due to the lack of efficacy, 34 patients had to discontinue because of adverse events, and 9 patients dropped out for both reasons. Gastrointestinal intolerance was the most frequent adverse event that led to the discontinuation of the drug, followed by myelosuppression. Five patients suffered from 6 malignancies occurring after a median of 4.5 years after cessation of treatment. Treatment of RA patients with 50 mg CYC per day resulted in a more favorable rate of serious adverse events and a markedly lower incidence of tumors compared to the treatment with 75 to 150 mg per day described in the literature. However, the long-term efficacy of this regimen was poor in our cohort.