Both gene and protein expression of IL-1 are highly upregulated in skin and synovium of patients with psoriatic arthritis (PsA) and psoriasis. IL-1 is known to play a key role in keratinocyte activation, matrix metalloproteinase upregulation, differentiation of osteoblast precursors into mature osteoblasts, angiogenesis and the development of erosive disease. Thus, the purpose of the study is to assess the effects of IL-1 inhibition on the clinical features of psoriasis and PsA disease activity, on synovial and cutaneous immunohistology and on magnetic resonance imaging (MRI) features of an affected knee joint.
To date, eight PsA patients (six male and two female, average age 41 years [22–61 years]) with active skin and joint disease have been enrolled for treatment over 12 weeks with 100 mg anakinra daily by subcutaneous injection. Physical examination, patient and physician global assessment of disease activity (on a scale of 0–3), tender and swollen joint scores, erythrocyte sedimentation rate, C-reactive protein and PASI scores were performed at all visits. Plain X-rays of hands, wrists, knees and feet were performed at baseline. A biopsy of a psoriatic plaque, multiple arthroscopic synovial biopsies and a MRI scan of an inflamed knee joint were performed at baseline and week 12. HAQ scores, patient assessment of disease activity and pain using visual analogue scales were obtained at weeks 0 and 12. PsA-QoL were calculated at weeks 0 and 12. The primary endpoint was the proportion of patients who met the Psoriatic Arthritis Response Criteria (PsARC) at 12 weeks.
Seven patients completed the study. One male patient was non-compliant with the study protocol and susbsequently withdrew before completion of the study. Baseline physical examination revealed psoriasis and active synovitis in all patients. Three of the seven patients (43%) met the PsARC at week 12. Mean HAQ scores improved from 1.23 (0.75–1.9) to 0.96 (0.25–1.6), while mean PsA-QoL scores changed from 22/46 (9–41) to 20/46 (5–40). Other relevant data are presented in Table 1.
This ongoing study has shown anakinra to be of modest benefit in patients with PsA. Further patient recruitment, MRI assessment and immunohistochemical analysis of tissue samples is ongoing.