Table 2. Details of studies with data on both efficacy and safety of selective glucocorticoid receptor modulator in comparison to a glucocorticoid.
| Author, year | SGRM tested | GC | Setting/model | Efficacy (SGRM compared to GC) | Safety (SGRM compared to GC) | ||
|---|---|---|---|---|---|---|---|
| Dewint et al., 2008 | Compound A | Dex | FLS cells derived from RA patients | Amount of cDNA of TNF = | NA | ||
| Amount of cDNA of MMP1 = | NA | ||||||
| Amount of cDNA of MMP3 = | NA | ||||||
| CIA mice | Arthritis score at day 8 of arthritis ↑ | NA | Serum levels of insulin ↓ | NA | |||
| Paw swelling at day 8 of arthritis = | NA | Normal histology of knee joints ↓ | NA | ||||
| mRNA G6P ↓ | NA | ||||||
| mRNA PEPCK ↓ | NA | ||||||
| Rauner et al., 2013 | Compound A | Dex | CIA mice | Arthritis score ↑ | NA | Bone loss ↓ | NA |
| Paw swelling ↑ | NA | Serum P1NP ↓ | NA | ||||
| Paw temperature ↓ | NA | Serum CTX-1 ↓ | NA | ||||
| Cellular infiltration in paws ↓ | NA | ||||||
| Cartilage destruction ↓ | NA | ||||||
| Inhibition of number of osteoclasts ↓ | NA | ||||||
| Supernatant from PBMCs from mice, ex vivo stimulated with collagen type II | TNF = | NA | |||||
| IFN-a = | NA | ||||||
| NF-ƙβ = | NA | ||||||
| mRNA expression in joint tissue from CIA mice | TNF ↑ | NA | |||||
| IL-6 ↓ | NA | ||||||
| Razavi et al., 2014 | Compound 14 | Pred | Mice inflammation model, LPS stimulated | IL-6 ↓ | NA | ||
| TNF = | NA | ||||||
| CIA mice | Arthritis score ↑ | NA | Insulin ↑ | NA | |||
| Body fat ↑ | NA | ||||||
| Triglycerides ↓ | NA | ||||||
| Free fatty acids ↑ | NA | ||||||
| Harcken et al., 2014 | Compound R18 and 21 | Pred | CIA mice | Arthritis score ↓ | NA | Osteocalcin ↑ | NA |
| Body fat ↑ | NA | ||||||
| Triglycerides ↑ | NA | ||||||
| Free fatty acids ↑ | NA | ||||||
| Insulin ↑ | NA | ||||||
| Femur cortical thickness = | S | ||||||
| Du et al., 2011 | Ginsenoside Rg1 | Dex | Inflamed paw model | Paw swelling ↑ | NS | ||
| CIA mice | Arthritis score = | NA | Body weight ↓ | NA | |||
| Blood glucose levels ↓ | S | ||||||
| Bone cortical thickness ↑ | NA | ||||||
| Bone content ↑ | S | ||||||
| Trabecular tibial number ↑ | S | ||||||
| Trabecular tibial thickness ↑ | NS | ||||||
| Trabecular tibial separation ↑ | S | ||||||
| Stock et al., 2017 | PF-04171327 | Pred | Phase 2 RCT, 86 RA patients, 2 weeks treatment | DAS28-4 (CRP) improvement ↑ | S | Fasting glucose = | NS |
| Plasma cortisol ↑ | S | ||||||
| Adverse events = | NA | ||||||
| Mean osteocalcin levels = | NA | ||||||
| Mean uNTX-1 levels = | NA | ||||||
Six studies reporting results on both efficacy and safety of SGRMs compared to GCs are depicted, only studies that reported efficacy and safety of both SGRM and GC are shown in this table. Results have been summarized for each SGRM if multiple dosing schemes were used. SGRM: selective glucocorticoid receptor modulator; GC: glucocorticoid; pred: prednisone, dex: dexamethasone; FLS: fibroblast-like synoviocytes; CIA: collagen induced arthritis; cDNA: copy DNA; TNF: tumor necrosis factor; MMP: matrix metalloproteinase; P1NP: N-terminal propeptide of type 1 collagen; CTX1: collagen type 1 cross-linked C-telopeptide; PBMCs: peripheral blood mononuclear cells; IFN-α: interferon alpha; NF-ƙβ: Nuclear Factor kappa-light-chain-enhancer of activated B cells; mRNA: messenger ribonucleic acid; RA: rheumatoid arthritis; DAS28-4 (CRP): disease activity score using 28 joints and c-reactive protein with 4 variables; IL-6: interleukin 6; uNTX-1: N-terminal telopeptide 1 in urine; NA: not statistically analyzed; NS: not significant; S: significant; RCT: randomized controlled trial; ↑: results higher for SGRM compared to GC; ↓: results lower for SGRM compared to GC; =: results similar for SGRM compared to GC.