Background: Ustekinumab, a human antibody to IL 12/23p40 has recently been approved for the treatment of patients with moderate to severe Crohn's disease, who have had an inaedequate response, lost response or were intolerant to either conventional therapy or TNF antagonists. Ustekinumab has already been approved for the therapy of patients with psoriasis and psoriatic arthritis. Psoriasis as a paradoxal inflammation of the skin can be seen by patients treated with TNF antagonists.
Methods: Patients with a TNF antagonist induced psoriasis and with loss of response to TNF antagonists were treated with ustekinumab. All patients had a chronic active disease course with a CDAI score >220 and <450 at the start of the ustekinumab therapy. Patients were treated with 90 mg ustekinumab subcutaneously every four weeks. CDAI, CRP and calprotectin were assessed at baseline and week 8, 12, 24, 36, 48 and 54 after treatment, when patients were seen again as part of standard clinical care. Sonography and ileocolonoscopy was performed at baseline, week 12 and week 54. SES-CDEIS was assed at baseline, week 12 and week 54. Response was defined as a >70 CDAI decrease and remission as a <150 CDAI.
Results: 85 patients were followed up. The median disease duration was 8.3yrs and mean baseline CDAI was 298. Mean baseline fecal calprotectin was 483mg/kg, mean baseline CRP 9.8 mg/l. The median baseline SES-CDEIS was 13.5. 11 (12.9%) patients finished treatment before week 54 due to a loss of response or intolerance. At week 8 mean CDAI and CRP were 269 and 6.8 mg/l, calprotectin 359 mg/kg. Mean CDAI, CRP, calprotectin and SES-CDEIS at week 12 were 232, 5.1 mg/l, 278 mg/kg, 10.5. At week 54 mean CDAI, CRP, calprotectin and SES-CDEIS were 171, 3.3mg/l, 198 mg/kg and 5.9. 11 (14.9%), 40 (54.1%) and 45 patients (60.8%) had a response at week 8, 12 and 54. Remission was seen in 0 (0%), 6 (8.1%) and 30 (40.5%) patients at week 8, 12 and week 54, respectively Psoriatic skin lesions were improved in 87.1% of the patients. No severe side effects were seen.
Conclusions: In this special cohort of patients with the TNF induced psoriasis and failure or loss of response of at least two TNF antagonists induction time of remission/response took longer than seen in clinical trials. This might be due to the fact that induction therapy with i.v. ustekinumab was not available at that time. But the therapy was well tolerated and maintenance treatment with ustekinumab was successful.