| Disease . | Strategy . | Efficacy . | Adverse events . | References . |
|---|---|---|---|---|
| SSc | Patients with early-stage diffuse SSc (n = 45) were treated intravenously with the anti–TGF-β1 antibody CAT-192 (metelimumab) or placebo. | No effect of anti–TGF-β1 treatment on cutaneous disease, assessed through the MRSS; TGF-β1 inhibition did not affect levels of circulating biomarkers of collagen metabolism. | Adverse events (gastrointestinal, respiratory, and cutaneous) were frequent in both control and treatment groups. Although the incidence of adverse events and serious adverse events was higher in treated patients, this was considered consistent with the high morbidity of SSc and was not attributed to the use of medication. | Denton et al., 2007 |
| SSc | Patients with early diffuse cutaneous SSc (n = 15) were treated with fresolimumab, a neutralizing antibody targeting all three TGF-β isoforms. | TGF-β neutralization rapidly improved skin disease, decreasing MRSS. The clinical response was associated with attenuated expression of fibrosis-associated genes and reduced myofibroblast infiltration in the affected skin. | Bleeding episodes (gastrointestinal bleeding, epistaxis, gingival bleeding) and anemia (defined as a >10% decrease in hemoglobin) were the most common adverse events in fresolimumab-treated patients. | Rice et al., 2015 |
| FSGS | In this phase I study, patients with treatment-resistant FSGS were treated with fresolimumab (single dose, n = 16). | Proteinuria and other efficacy measures tended to fluctuate over the course of the study. There was no evidence of any treatment-related changes. | A pustular rash was the most frequently reported treatment-emergent adverse event. | Trachtman et al., 2011 |
| FSGS | In this phase II double-blind study, patients with steroid-resistant FSGS were treated with fresolimumab or placebo (n = 36). | No significant effects of TGF-β inhibition. The absence of effects was attributed to underpowered design. | Treatment-emergent adverse events (including rash, headache, and gingival bleeding) were noted in treated patients; however, overall fresolimumab was safe and well tolerated. | Vincenti et al., 2017 |
| Diabetic nephropathy | Patients with advanced diabetic nephropathy were treated with a neutralizing anti–TGF-β1 antibody or placebo (n = 417). | Early discontinuation due to lack of efficacy. Anti–TGF-β1 had no significant effects on renal function and did not affect proteinuria. Serum biomarkers reflecting matrix remodeling (fibronectin, high molecular weight collagen IV, and MMP7) were not affected. | Adverse events were common in both treated and untreated patients, reflecting the severity of underlying nephropathy; however, anti–TGF-β1 did not affect the incidence of adverse events. | Voelker et al., 2017 |
| Conjunctival scarring following glaucoma surgery | Patients undergoing trabeculectomy for glaucoma (n = 24) were treated with subconjunctival injections of lerdelimumab (CAT-152), an anti–TGF-β2 neutralizing antibody with cross-reactivity to TGF-β3. | Patients receiving CAT-152 had greater early reduction in intraocular pressure. The study may have been underpowered to detect differences in other endpoints. | No significant differences in the incidence of complications between groups. | Siriwardena et al., 2002 |
| Conjunctival scarring | Two randomized double-blind clinical trials examined the safety and efficacy of subconjunctival CAT-152 injection in patients undergoing trabeculectomy for uncontrolled glaucoma. | There were no significant effects of TGF-β2 inhibition on surgical success. | No significant adverse events could be attributed to local TGF-β inhibition. | Grehn et al., 2007; Khaw et al., 2007 |
| Disease . | Strategy . | Efficacy . | Adverse events . | References . |
|---|---|---|---|---|
| SSc | Patients with early-stage diffuse SSc (n = 45) were treated intravenously with the anti–TGF-β1 antibody CAT-192 (metelimumab) or placebo. | No effect of anti–TGF-β1 treatment on cutaneous disease, assessed through the MRSS; TGF-β1 inhibition did not affect levels of circulating biomarkers of collagen metabolism. | Adverse events (gastrointestinal, respiratory, and cutaneous) were frequent in both control and treatment groups. Although the incidence of adverse events and serious adverse events was higher in treated patients, this was considered consistent with the high morbidity of SSc and was not attributed to the use of medication. | Denton et al., 2007 |
| SSc | Patients with early diffuse cutaneous SSc (n = 15) were treated with fresolimumab, a neutralizing antibody targeting all three TGF-β isoforms. | TGF-β neutralization rapidly improved skin disease, decreasing MRSS. The clinical response was associated with attenuated expression of fibrosis-associated genes and reduced myofibroblast infiltration in the affected skin. | Bleeding episodes (gastrointestinal bleeding, epistaxis, gingival bleeding) and anemia (defined as a >10% decrease in hemoglobin) were the most common adverse events in fresolimumab-treated patients. | Rice et al., 2015 |
| FSGS | In this phase I study, patients with treatment-resistant FSGS were treated with fresolimumab (single dose, n = 16). | Proteinuria and other efficacy measures tended to fluctuate over the course of the study. There was no evidence of any treatment-related changes. | A pustular rash was the most frequently reported treatment-emergent adverse event. | Trachtman et al., 2011 |
| FSGS | In this phase II double-blind study, patients with steroid-resistant FSGS were treated with fresolimumab or placebo (n = 36). | No significant effects of TGF-β inhibition. The absence of effects was attributed to underpowered design. | Treatment-emergent adverse events (including rash, headache, and gingival bleeding) were noted in treated patients; however, overall fresolimumab was safe and well tolerated. | Vincenti et al., 2017 |
| Diabetic nephropathy | Patients with advanced diabetic nephropathy were treated with a neutralizing anti–TGF-β1 antibody or placebo (n = 417). | Early discontinuation due to lack of efficacy. Anti–TGF-β1 had no significant effects on renal function and did not affect proteinuria. Serum biomarkers reflecting matrix remodeling (fibronectin, high molecular weight collagen IV, and MMP7) were not affected. | Adverse events were common in both treated and untreated patients, reflecting the severity of underlying nephropathy; however, anti–TGF-β1 did not affect the incidence of adverse events. | Voelker et al., 2017 |
| Conjunctival scarring following glaucoma surgery | Patients undergoing trabeculectomy for glaucoma (n = 24) were treated with subconjunctival injections of lerdelimumab (CAT-152), an anti–TGF-β2 neutralizing antibody with cross-reactivity to TGF-β3. | Patients receiving CAT-152 had greater early reduction in intraocular pressure. The study may have been underpowered to detect differences in other endpoints. | No significant differences in the incidence of complications between groups. | Siriwardena et al., 2002 |
| Conjunctival scarring | Two randomized double-blind clinical trials examined the safety and efficacy of subconjunctival CAT-152 injection in patients undergoing trabeculectomy for uncontrolled glaucoma. | There were no significant effects of TGF-β2 inhibition on surgical success. | No significant adverse events could be attributed to local TGF-β inhibition. | Grehn et al., 2007; Khaw et al., 2007 |
FSGS, focal segmental glomerulosclerosis; MRSS, modified Rodnan skin thickness score; SSc, systemic sclerosis.