Obesity was associated with inferior response to anti-TNF therapy in both RCTs (20 studies; OR, 1.50 [1.24–1.80], I2 = 40%) (Panel A in S3 Fig)[41, 44, 48, 52, 54, 56–60, 65–67, 69, 71–73, 75, 79] and observational studies (34 studies; OR, 1.68 [1.48–2.00], I2 = 78%) (Panel B in S3 Fig), without significant difference between subgroups (pinteraction = 0.39).[14, 26–33, 40, 42, 43, 45–47, 49–51, 53, 55, 61–64, 68, 70, 74, 76–78, 80]. Here, TNF is linked to obesity due to melanocortin 4 receptor deficiency.