D-penicillamine in early rheumatoid arthritis: experience from a 2-year double blind placebo controlled study

Clin Exp Rheumatol. 1996 Nov-Dec;14(6):625-31.


Objective: To evaluate the usefulness of early treatment with D-Penicillamine (DPA) in rheumatoid arthritis.

Methods: The patients were recruited from a Swedish early RA cohort comprising 180 patients. All patients experiencing active and/or erosive disease 2 years from onset were asked to participate in a 2-year placebo-controlled DPA trial. Previous treatment with slow-acting anti-rheumatic drugs (SAARDs) or oral corticosteroids was not allowed. The main outcome variable was radiographic progression in the hands and feet evaluated according to Larsen. Clinical assessment including the Ritchie index, active joint count, and the HAQ-disability index was performed every 6th month. Patients were included in the analyses of efficacy until the endpoint of therapy.

Results: 111/180 patients were eligible for treatment, and 74 agreed to participate in the trial. 21/33 patients on DPA and 22/41 on placebo completed the study. More patients taking placebo stopped due to lack of response (p < 0.01). 27% of the patients on DPA were withdrawn due to side effects. Radiographic deterioration increased but most clinical variables improved in both trial arms. A large inter-individual variation was observed. The only significant difference in trend over 2 years between DPA and placebo was found for joint tenderness. However, the median trends for most clinical variables showed a more positive effect for DPA. The 37 patients who refused to participate in the trial in general fared somewhat worse than patients taking DPA and somewhat better than patients taking placebo. The remission rate was about the same in all 3 groups (12-13.5%).

Conclusions: About two-thirds of all early definite RA patients were eligible for treatment using current criteria. Psychological readiness for early therapy was fairly modest with a high refusal rate. The difference in efficacy between DPA and placebo was small, but was in favour of DPA for most clinical variables. However, only joint tenderness showed a significantly better trend. No significant slowing of radiographic progression by DPA was found.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / drug therapy*
  • Chloroquine / adverse effects
  • Chloroquine / therapeutic use
  • Disease Progression
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Penicillamine / adverse effects
  • Penicillamine / therapeutic use*
  • Radiography
  • Retrospective Studies
  • Sulfasalazine / adverse effects
  • Sulfasalazine / therapeutic use
  • Treatment Outcome


  • Antirheumatic Agents
  • Sulfasalazine
  • Chloroquine
  • Penicillamine