SummaryBackgroundPersonalised medicine, including biomarkers for treatment selection, may provide new algorithms for more effective treatment of patients. Genetic variation may impact drug response and genetic markers could help selecting the best treatment strategy for the individual patient.AimTo identify polymorphisms and candidate genes from the literature that are associated with anti‐tumour necrosis factor (TNF) treatment response in patients with inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis.MethodsWe performed a PubMed literature search and retrieved studies reporting original data on association between polymorphisms and anti‐TNF treatment response and conducted a meta‐analysis.ResultsA functional polymorphism in FCGR3A was significantly associated with anti‐TNF treatment response among CD patients using biological response criterion (decrease in C‐reactive protein, levels). Meta‐analyses showed that polymorphisms in TLR2 (rs3804099, OR (95% CI) = 2.17 (1.35–3.47)], rs11938228 [OR = 0.64 (0.43–0.96)], TLR4 (rs5030728) [OR = 3.18 (1.63–6.21)], TLR9 (rs352139) [OR = 0.43 (0.21–0.88)], TNFRSF1A (rs4149570) [OR = 2.06 (1.02–4.17)], IFNG (rs2430561) [OR = 1.66 (1.05–2.63)], IL6 (rs10499563) [OR = 1.65 (1.04–2.63)] and IL1B (rs4848306) [OR = 1.88 (1.05–3.35)] were significantly associated with response among IBD patients using clinical response criteria. A positive predictive value of 0.96 was achieved by combining five genetic markers in an explorative analysis.ConclusionsThere are no genetic markers currently available which are adequately predictive of anti‐TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis‐free approaches, testing a large number of polymorphisms in large, well‐characterised cohorts, are required in order to identify genetic profiles with larger effect sizes, which could be employed as biomarkers for treatment selection in clinical settings.

IMPORTANCE Individual placement and support (IPS) seems to be an effective vocational intervention for people with severe mental illness, but its effects have not yet been shown in the Danish welfare model. Also, effects may be enhanced by adding cognitive remediation and work-focused social skills training (IPS with enhancements [IPSE]).OBJECTIVES To investigate the effects of IPS vs IPSE vs service as usual (SAU) on a population of individuals with severe mental illness in Denmark. DESIGN, SETTING, AND PARTICIPANTSThis was an investigator-initiated, 3-group, parallel, assessor-blinded randomized clinical trial that used early-intervention teams or community mental health services in 3 Danish cities to recruit participants with severe mental illness. Participants were randomly assigned to receive IPS, IPSE, or SAU from November 2012 to February 2016, and follow-up continued until August 2017. INTERVENTIONS Participants allocated to the IPS intervention received vocational support per the principles of the IPS model. Participants in the IPSE arm received cognitive remediation and social skills training in addition to IPS. The group receiving SAU received vocational rehabilitation at the Danish job centers. MAIN OUTCOMES AND MEASURES The primary outcome was the number of hours in competitive employment or education during the 18-month follow-up. Secondary outcomes included intergroup differences in employment or education at any point during follow-up; time to employment or education; and cognitive and social functioning, self-esteem, and self-efficacy. RESULTS Of the 720 included participants (mean [SD] age, 32.8 [9.9] years; 276 [38.3%] women), 243 received IPS, 238 received IPSE, and 239 received SAU. Most participants ( 551[76.5%]) were diagnosed with a schizophrenia spectrum disorder. During the 18-month follow-up, the IPSE group worked or studied a mean (SD) of 488.1 (735.6) hours, compared with 340.8 (573.8) hours in the group receiving SAU (success-rate difference [SRD], 0.151 [95% CI, 0.01-0.295]; P = .016). The mean (SD) in the IPS group was 411 (656.9) (SRD, 0.127 [95% CI, −0.017 to 0.276]; P = .004). There was no difference between IPS and IPSE in any vocational outcomes, and the 3 groups showed no differences in any nonvocational outcomes, except that the IPS and IPSE groups were more satisfied with the services received than the group receiving SAU (IPS vs SAU: SRD, 0.310 [95% CI, 0.167-0.445]); IPSE vs SAU: SRD, 0.341 [95% CI, 0.187-0.478]).CONCLUSIONS AND RELEVANCE Compared with SAU, IPS and IPSE seem to be viable routes to increase employment and education rates in people with severe mental illness in Denmark, but no additional effects were observed by enhancing IPS.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects ~1% of the Caucasian population. Over the last decades, the availability of biological drugs targeting the proinflammatory cytokine tumour necrosis factor α, anti-TNF drugs, has improved the treatment of patients with RA. However, one-third of the patients do not respond to the treatment. We wanted to evaluate the status of pharmacogenomics of anti-TNF treatment. We performed a PubMed literature search and all studies reporting original data on associations between genetic variants and anti-TNF treatment response in RA patients were included and results evaluated by meta-analysis. In total, 25 single nucleotide polymorphisms were found to be associated with anti-TNF treatment response in RA (19 from genome-wide association studies and 6 from the meta-analyses), and these map to genes involved in T cell function, NFκB and TNF signalling pathways (including CTCN5, TEC, PTPRC, FCGR2A, NFKBIB, FCGR2A, IRAK3). Explorative prediction analyses found that biomarkers for clinical treatment selection are not yet available.