An open study of pentoxyfylline and thalidomide as adjuvant therapy in the treatment of rheumatoid arthritis.
OBJECTIVE
Dysregulation of tumour necrosis factor alpha (TNF alpha) production is thought to be important in rheumatoid arthritis. Since pentoxifylline and thalidomide inhibit endotoxin induced TNF production in vitro, these drugs were tested in an open study in rheumatoid arthritis patients to assess toxicity, the effect on TNF production, and the antiarthritic effects.


METHODS
12 patients with active rheumatoid arthritis were treated with 1200 mg pentoxifylline and 100 mg thalidomide a day during 12 weeks. In addition, TNF production was assessed by ex vivo whole blood cultures stimulated with endotoxin.


RESULTS
Adverse events such as xerostomia, drowsiness, and constipation occurred in almost all patients, which led to discontinuation in three. The drugs halved the TNF production capacity during treatment (ANOVA, P < 0.03) whereas production capacity of interleukin (IL) 6, IL-10, and IL-12 was not affected. Of the nine patients who completed the study, five fulfilled the ACR-20% response criteria after 12 weeks of treatment.


CONCLUSIONS
Although pentoxifylline/thalidomide reduced the production capacity of TNF, the benefit/side effects ratio was poor due to multiple adverse effects, while clinical observation suggests limited efficacy.
Huizinga
T W
TW
Department of Rheumatology, University Hospital Leiden, The Netherlands.
Dijkmans
B A
BA
van der Velde
E A
EA
van de Pouw Kraan
T C
TC
Verweij
C L
CL
Breedveld
F C
FC
D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D006403:Hematologic Tests; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D010431:Pentoxifylline / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013792:Thalidomide / Q000009:adverse effects / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D013792:Thalidomide; D010431:Pentoxifylline