Paradoxical adverse events of anti-tumour necrosis factor therapy for spondyloarthropathies: a retrospective study.

OBJECTIVES: Several paradoxical adverse events (PAEs), e.g. IBDs, acute anterior uveitis (AAU) and psoriasis, have been described in patients taking anti-TNF drugs. This retrospective study aimed to describe the different PAEs that have occurred in a population of SpA patients treated with anti-TNF drugs, and to determine whether they are drug specific. METHODS: Since 2000, we have followed 296 patients with SpA [198 AS, 21 SpA associated with IBD (9 ulcerative colitis, 12 Crohn's disease) and 77 psoriatic arthritis] treated with at least one anti-TNF drug (infliximab, etanercept or adalimumab), and 112 SpA patients treated only with conventional DMARDs who served as controls. Considering the cumulative time of exposure to each anti-TNF agent, the frequencies of new-onset PAEs in exposed patients were calculated. RESULTS: Respective cumulative exposure times were 287, 290 and 62 patient-years for infliximab, etanercept and adalimumab. We observed the following PAEs: five psoriasis (three under infliximab and one with etanercept or adalimumab), three AAU (1/100 patient-years, all under etanercept) and four IBD (three under etanercept and one under infliximab). There was no significant association among any of these PAEs and a specific anti-TNF agent; nor significant difference in the overall PAEs among patients receiving anti-TNF drugs or controls (P = 0.303), the latter experiencing two psoriasis and three AAU. CONCLUSIONS: Undesirable side effects--IBD, AAU and psoriasis--may appear with anti-TNF drugs. Even if they are, a priori, paradoxical, no evidence supports any PAEs to be anti-TNF agent-specific in SpA.

Switching from an anti-TNF monoclonal antibody to soluble TNF-receptor yields better results than vice versa: An observational retrospective study of 72 rheumatoid arthritis switchers.

OBJECTIVES: To evaluate the benefits for rheumatoid arthritis (RA) patients of switching from one tumor necrosis factor inhibitor (TNFi) to another based on reason for change (primary failure, escape or intolerance) and molecule-switching order. METHODS: Between 2000 and 2008, 356 RA patients prescribed a TNFi (infliximab [IFX], etanercept [ETA] or adalimumab [ADA]) and undergoing standardized evaluation were included in this retrospective study. Detailed demographic, clinical and biological data were collected before first biologic use and ≤6 months later to evaluate response based on EULAR-criteria. Primary failure, escape or intolerance of first TNFi triggered switch to another TNFi, the response of which was evaluated 6 months later. Propensity score then measured any interaction with baseline variables. RESULTS: Of the 356 RA patients, 38 switched from IFX/ADA to ETA, 26 from ETA to IFX/ADA, and eight from one monoclonal antibody (mAb; IFX/ADA) to another. Clinical parameters for switchers and non-switchers were comparable. Switchers changed therapies because of primary failure (36.1%), escape (33.3%), or intolerance (30.6%), with no difference found in these subgroups. More switchers responded to the second TNFi than the first (P<0.01), respectively, regardless of switch (ETA to IFX/ADA: 50 vs. 23.1% [P<0.05]; IFX/ADA to ETA: 57.9 vs. 15.8% [P<0.001]) or reason for changing. In addition, DAS28 decreased more with the second antagonist (P<0.001) and regardless of molecules switched (P<0.01). Survival of the second TNFi was significantly longer with switch from mAb to the soluble receptor than vice versa (P<0.05). DISCUSSION: Overall, any switching from one TNFi to another, especially mAb to soluble receptor, was often beneficial for RA patients.