Background About 7% of patients (pts) with arthritis are patients with psoriatic arthritis (PsA). After 10 years of PsA 55% of pts have deformity more than 5 joints. Only one trial examined the efficacyand safety of monotherapy (MONO) with Leflunomide (LF) in PsA . Until now, remain under-explored the efficacy and toxicity of LF combination therapy (COMBI) with non-biological disease-modifying antirheumatic drugs (DMARDs) in PsA.
Objectives To evaluate the efficacy and toxicity of LF MONO compared with LF COMBI in adults with PsA.
Methods 63 PsA pts with peripheral arthritis received LF (20 mg/day) alone (32 pts) or in addition to Methotrexate (mean dose 12,7±3,0 mg/week) (19 pts with inadequate response) or Sulfasalazine (mean dose 2.0 g/day) (13 pts). Response was evaluated according to PsARC and PASI criteria, Health Assessment Questionnaire (HAQ), Disease Activity Score (DAS) and DAS C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum levels of CRP, matrix metalloproteinase-3 (MMP-3) and pyridinoline after 3 months of the treatment. Before the study, both groups did not differ significantly from the values of DAS, DASCRP, PASI, HAQ and the level of laboratory markers.
Results The difference (mean change per patient) week 0-week 12 (COMBI, MONO respectively) was: score (228 max.) of tender joints: -28.7, -21.5; score (222 max.) of swollen joints: -12.3, -6.33, Ritchie index: -12.2, -9,4; duration of morning stiffness (minutes): -133.6, -46.7; DAS: -1.52, -1.08; DASCRP: -1.50, -1.06; HAQ: -0.26, -0.38; PASI: -8.97, -3.96; ESR (mm/h): -3.80, -2.70; CRP (mg/l): -1.35, -1.36; MMP-3 (ng/ml): -4.83, -1.89; pyridinoline (nM/l): -0.18, -0.17. All changes in both groups were statistically significant. The efficacy in COMBI group was significantly higher on the score of swollen joints, duration of morning stiffness, Ritchie index, DAS, DASCRP and PASIcompared with MONO. Among thelaboratory parametersonly decrease of MMP-3 was significantly greater in COMBI group and only the change of MMP-3 levels correlated with the dynamics of clinical parameters - the score of swollen joints (r=0.29, p<0.03) and duration of morning stiffness (r=0.52, p<0.001). The number of PsARC and PASI50 responders constituted 60.0% and 51.7% in MONO group vs 70.0% and 36.7% in COMBI respectively (p>0.05). The number of pts who have had good and moderate response according to DASCRP were significantly higher in COMBI group compared with MONO: 86.7% vs 63.3% (ϕ=2.15, p<0.05).
During the study 3 pts prematurely (up to 4 weeks of treatment) discontinued the drug because of side effects (one patient because of dermatitis, sensory neuropathy, and by increasing the level of ALT>3 times above the ULN). In 14 pts (23.3%) observed adverse events (dyspepsia, alopecia, dermatitis, increased ALT/AST<2 times above the ULN, cardialgia, neuropathy) that did not require discontinuation. Among all 17 cases of adverse events 58.8% occurred in COMBI group and 41.2% in group of LF MONO (p>0.05).
Conclusions The efficacy of LF COMBI is higher than the LF MONO in PsA. Among the laboratory parameters serum level of MMP-3 more fully reflects the dynamics of the clinical parameters of joint inflammation in pts with PsA. The tolerability in both groups did not significantly differ.
Kaltwasser JP et al. Arthritis Rheum 2004;50(6):1939-1950.
Disclosure of Interest None Declared