To the Editor: We read with great interest the letter of Hirten et al. (1) "Vedolizumab and infliximab combination therapy in the treatment of Crohn's disease". The authors reported the efficacy of administration of two vedolizumab infusion during an infliximab (IFX) maintenance therapy. Here we would like to report the association of ustekinumab (UTK) with anti-TNF in three patients with paradoxical psoriasis under anti-TNF therapy for inflammatory bowel disease (IBD). The first case is a 36-yr-old man with ileocolonic Crohn's disease (CD) in deep remission with adalimumab (ADA). He developed an inverse psoriasis resistant to topical therapies and acitretin. He received two UTK s.c. (SC) injections (90 and 45 mg) in association with ADA. After 2 mo, psoriasis lesions were unchanged and ADA had to be stopped. The second case is a 49-yr-old man in clin. remission with IFX for stricturing ileal CD. He received three UTK SC injections (90, 45, and 45 mg) without any effect on psoriasis lesions. The last case is a 56-yr-old woman with ulcerative pancolitis in deep remission with IFX therapy. She developed a psoriasis resistant to topical therapy and methotrexate. Three injections of UTK (90, 45, and 45 mg) were performed in association with IFX without any efficacy on cutaneous lesions. Both UTK and IFX were stopped. All patients stay in intestinal remission during combination therapy and no adverse events were observed after a median follow-up of 21 mo after the initiation of UTK. Paradoxical psoriasis is observed in up to 20% of patients with IBD treated by anti-TNF. Treatment withdrawal is required in up to one-third of these patients despite of its effectiveness on intestinal disease (2). The efficacy of UTK, an IL12/23 inhibitor, has been demonstrated in a randomized controlled trial (RCT) for the treatment of severe psoriasis, as well as in observational studies of paradoxical psoriasis after stopping anti-TNF (3, 4). More recently, UTK was evaluated in a large RCT for the induction and maintenance of CD (5). Even if larger studies have to be done to confirm our results, the association of UTK with anti-TNF was not effective in the treatment of paradoxical psoriasis in these three patients. However, this association of two biotherapies in IBD patients seems to be safe and well tolerated. Antagonizing two or more pro-inflammatory cytokines, or associating cytokine antagonists to T-cell activation or migration blockers, could be a promising way to obtain an additive or a synergistic effect in the treatment of refractory IBD (5). The development of this new strategy could be limited by the fear of adverse events and generalized immunosuppression and need long-term safety data.