Table 2.
A non-exhaustive summary of recent interventional studies investigating pharmacogenomics of relevance to primary care. 1° = primary endpoint, 2° = secondary endpoints, RCT = randomised controlled trial, SoC = standard of care treatment.
| Study | N | Genes | Treatment | Design | Duration | Intervention | Comparator | Endpoint | Outcome |
|---|---|---|---|---|---|---|---|---|---|
| Greden et al. 2019 (GUIDED) [12] | 1167 | Panel of 8 genes (including CYP2C19 and CYP2D6) | SSRI, SNRI, TCA, other antidepressants, typical and atypical antipsychotics | RCT | 24 weeks | PGx guided treatment | Standard of care treatment | 1°–Symptoms (8 weeks) 2°–Response rate and remission (8 weeks) |
1°–Symptom ↓ of 27.2% PGx vs. 24.4% SoC (p = 0.107) 2°–Response: 26.0% vs. 19.9% (p = 0.013) Remission: 15.3% vs. 10.1% (p = 0.007) |
| Perez et al. 2017 [13] | 316 | Panel of 30 genes (including CYP2C19 and CYP2D6) | SSRI, SNRI, TCA, MAOI, other antidepressants | RCT | 12 weeks | PGx guided treatment | Standard of care treatment | 1°–% of patients with sustained response (12 weeks) 2°–Responder rate and side effect burden (12 weeks) |
1°–38.5% PGx vs. 34.4% SoC (p = 0.4735) 2°–Responder rate: 47.8% vs. 36.1% (p = 0.0476) 2°–Side effect burden: 68.5% vs. 51.4% (p = 0.0260) |
| Bradley et al. 2018 [14] | 685 | Panel of 10 genes (including CYP2C19 and CYP2D6) | SSRI, SNRI, TCA, other antidepressants, benzodiazepines, buspirone | RCT | 12 weeks | PGx guided treatment | Standard of care treatment | Remission & response depression (12 weeks) Symptom severity & response anxiety (12 weeks) |
Depression: Remission: 35% PGx vs. 13% SoC (p = 0.02) Response: 73% vs. 36% (p = 0.001) Anxiety: Symptom ↓ of 54% vs. 42% (p = 0.02) Response: 63% vs. 50% (p = 0.04) |
| Pirmohamed et al. 2013 (EU-PACT) [15] | 455 | CYP2C9 and VKORC1 | Warfarin | RCT | 12 weeks | PGx guided treatment | Standard of care treatment | 1°–% of time in INR range 2.0 to 3.0 | 1°–67.4% PGx vs. 60.3% SoC (p < 0.001) |
| Kimmel et al. 2013 (COAG) [16] | 1015 | CYP2C9 and VKORC1 | Warfarin | RCT | 28 days | PGx guided treatment | Clinical dosing algorithm | 1°–% of time in INR range 2.0 to 3.0 | 1°–45.2% PGx vs. 45.4% SoC (p = 0.91) |
| Gage et al., 2017 (GIFT) [17] | 1650 | CYP2C9, VKORC1 and CYP4F2 | Warfarin | RCT | PGx guided treatment | Clinical dosing algorithm | 1°–composite of major bleeding, INR ≥ 4, death (all in 30 days) or VTE (in 60 days) | 1°–10.8% PGx vs. 14.7% SoC (p = 0.02) | |
| Pereira et al. 2020 (TAILOR-PCI) [18] | 5302 | CYP2C19 | Clopidogrel | RCT | 12 months | PGx guided oral P2Y12 inhibitor treatment | Standard of care (Clopidogrel) | 1°–composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia (12 months) | 1°–in 4.0% PGx LOF carriers vs. 5.9% SoC LOF carriers (p = 0.06) |
| Claassens et al. 2019 (POPular) [19] | 2488 | CYP2C19 | Clopidogrel | RCT | 12 months | PGx guided oral P2Y12 inhibitor Tx | Standard of care (Ticagrelor or prasugrel) | 1°–Net adverse clinical events (12 months) 1°–Major or minor bleeding (12 months) |
Net events: 5.1% PGx vs. 5.9% SoC (p < 0.001 for noninferiority) Bleeding: 9.8% vs. 12.5% (p = 0.04) |
| Ko et al. 2015 [20] | 2926 | HLA-B*58:01 | Allopurinol | Cohort | 9 months | Allopurinol avoided in HLA-B*58:01 +ve patients | Allopurinol given in HLA-B*58:01-ve patients | 1°–Incidence of SCARs in cohort compared to historical national average | 1°–No cases of SCARs in prospective cohort (within 9 month follow up) vs. 7 cases to be expected based on historical average (0.3% per year), p = 0.0026 |