[Therapy of rheumatoid arthritis with methotrexate. Claims data analysis of treatment patterns]. / Therapie der rheumatoiden Arthritis mit Methotrexat. Analyse von Versorgungsaspekten anhand von GKV-Routinedaten.

Methotrexate (MTX) is the most important disease-modifying antirheumatic drug (DMARD) and is recommended by national and international guidelines as the first choice for treatment of rheumatoid arthritis (RA). Recent studies reporting prescription data of MTX captured only patients who were treated by rheumatologists. Therefore, the aim of the present study was to analyse several aspects of the prescription of MTX based on claims data. Outpatient and inpatient diagnoses as well as prescription data was available for 9579 RA patients for the years 2005-2008. Of the patients 45% were treated exclusively with parenteral MTX, 8% were treated exclusively with oral MTX and 48% switched between both forms of application. The average weekly dosage presribed in 70% of the patients was between 10 and 25 mg. The most common DMARD combination was MTX plus leflunomide with 16%. In 16% RA patients were treated with a combination of MTX and TNF-α inhibitors. Glucocorticoids were prescribed temporarily in 81% together with MTX and supplementation with folic acid was given only in 65%. The results of this study provide important insights into the drug supply of MTX to RA patients in the German statutory health care sector. In particular, the high frequency of prescriptions of parenteral MTX and the inadequate prescription of folic acid are different from the recently published multinational recommendations of the 3E initiative for the use of MTX.

The non-mevalonate isoprenoid biosynthesis of plants as a test system for new herbicides and drugs against pathogenic bacteria and the malaria parasite.

Higher plants and several photosynthetic algae contain the plastidic 1-deoxy-D-xylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate pathway (DOXP/MEP pathway) for isoprenoid biosynthesis. The first four enzymes and their genes are known of this novel pathway. All of the ca. 10 enzymes of this isoprenoid pathway are potential targets for new classes of herbicides. Since the DOXP/MEP pathway also occurs in several pathogenic bacteria, such as Mycobacterium tuberculosis, and in the malaria parasite Plasmodium falciparum, all inhibitors and potential herbicides of the DOXP/MEP pathway in plants are also potential drugs against pathogenic bacteria and the malaria parasite. Plants with their easily to handle DOXP/MEP-pathway are thus very suitable test-systems also for new drugs against pathogenic bacteria and the malaria parasite as no particular security measures are required. In fact, the antibiotic herbicide fosmidomycin specifically inhibited not only the DOXP reductoisomerase in plants, but also that in bacteria and in the parasite P. falciparum, and cures malaria-infected mice. This is the first successful application of a herbicide of the novel isoprenoid pathway as a possible drug against malaria.

The non-mevalonate isoprenoid biosynthesis of plants as a test system for drugs against malaria and pathogenic bacteria.

Two plant test systems are presented in the search for new inhibitors of the non-mevalonate isoprenoid pathway. A derivative of clomazone appears to be an inhibitor of the deoxyxylulose 5-phosphate/methylerythritol 4-phosphate (DOXP/MEP) pathway of isoprenoid formation.