The invention provides a composition and use of a composition comprising a fusion protein and a first ligand in a ratio sufficient to increase therapeutic efficacy of the fusion protein in a subject, the fusion protein comprising an extracellular domain (ECD) of a first receptor and a second ligand, wherein the second ligand is capable of binding to a second receptor, wherein the first ligand is capable of binding to the first receptor, wherein the first and second ligands, and the first and second receptors, are TNF-family members, and wherein the first and second ligands are different, and the first and second receptors are different. The invention also provides a composition comprising Fn14-TRAIL fusion protein and TWEAK and use thereof for treating diseases or conditions associated with increased levels of TWEAK. The invention is further directed to use of Fn14-TRAIL fusion protein to treat diseases or conditions associated with increased levels of TWEAK.
