All patients
Age < 65y (younger) Age > 65y BRAF mutant BRAF wild type ECOG 0 ECOG 1 Gender, female Gender, male LDH > ULN LDH ≤ULN metastasis (brain) NO metastasis (brain) YES PD-L1 < 1% PD-L1 < 5% PD-L1 > 1% PD-L1 > 5% previous systemic treatment (%) previous systemic treatment NO (%) stage M0 stage M0/M1A/M1B stage M1A stage M1B stage M1C stage M1C (with brain metastasis)
Top evidence (RCT only, high risk of bias excluded)
Best available evidence (possibly low or very low)
All RCTs
All studies (RCT+OBS)
mML - 2nd line (L2), immune chekpoint inhibitors vs. Standard of Care (SoC), meta-analysis of study results Outcome TE 95% CI n k I2 ROB Pub. bias deaths (OS)detailed results CA184-024, 2011 0.72 [0.59; 0.87]
KEYNOTE-002 (10 mg/kg), 2015 0.74 [0.57; 0.96]
KEYNOTE-002 (2 mg/kg), 2015 0.86 [0.67; 1.10]
KEYNOTE-022, 2019 0.76 [0.41; 1.40]
0.76 [0.67 ; 0.87 ] CA184-024, 2011, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015, KEYNOTE-022, 2019 4 0% 1,341 moderate not evaluable deaths (OS) (extension)detailed results CA184-024, 2011 0.69 [0.57; 0.84]
0.69 [0.57 ; 0.84 ] CA184-024, 2011 1 0% NA not evaluable progression or deaths (PFS)detailed results CA184-024, 2011 0.76 [0.63; 0.92]
KEYNOTE-002 (10 mg/kg), 2015 0.50 [0.39; 0.64]
KEYNOTE-002 (2 mg/kg), 2015 0.57 [0.45; 0.73]
KEYNOTE-022, 2019 0.66 [0.40; 1.08]
0.61 [0.50 ; 0.76 ] CA184-024, 2011, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015, KEYNOTE-022, 2019 4 61% 1,341 moderate not evaluable DCRdetailed results CA184-024, 2011 1.15 [0.79; 1.68]
1.15 [0.79 ; 1.68 ] CA184-024, 2011 1 0% 502 NA not evaluable DORdetailed results KEYNOTE-022, 2019 0.41 [0.20; 0.83]
0.41 [0.20 ; 0.83 ] KEYNOTE-022, 2019 1 0% 81 NA not evaluable objective responses (ORR)detailed results CA184-024, 2011 1.56 [0.91; 2.65]
KEYNOTE-002 (10 mg/kg), 2015 8.16 [3.74; 17.80]
KEYNOTE-002 (2 mg/kg), 2015 6.11 [2.77; 13.47]
KEYNOTE-022, 2019 0.68 [0.32; 1.47]
2.67 [0.91 ; 7.79 ] CA184-024, 2011, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015, KEYNOTE-022, 2019 4 89% 1,341 low not evaluable AE (any grade)detailed results CA184-024, 2011 5.17 [1.48; 18.09]
KEYNOTE-022, 2019 2.03 [0.18; 23.06]
4.25 [1.40 ; 12.93 ] CA184-024, 2011, KEYNOTE-022, 2019 2 0% 618 low not evaluable AE (grade 3-4)detailed results CA184-024, 2011 3.39 [2.34; 4.94]
KEYNOTE-022, 2019 2.44 [1.17; 5.12]
3.17 [2.27 ; 4.43 ] CA184-024, 2011, KEYNOTE-022, 2019 2 0% 618 low not evaluable AE leading to death (grade 5)detailed results CA184-024, 2011 1.02 [0.02; 51.42]
KEYNOTE-022, 2019 4.10 [0.18; 92.93]
2.39 [0.21 ; 27.48 ] CA184-024, 2011, KEYNOTE-022, 2019 2 0% 618 low not evaluable AE leading to treatment discontinuation (any grade)detailed results KEYNOTE-022, 2019 2.58 [1.16; 5.75]
2.58 [1.16 ; 5.75 ] KEYNOTE-022, 2019 1 0% 120 NA not evaluable TRAE (any grade)detailed results CA184-024, 2011 5.64 [3.80; 8.35]
KEYNOTE-002 (10 mg/kg), 2015 0.76 [0.45; 1.26]
KEYNOTE-002 (2 mg/kg), 2015 0.56 [0.34; 0.93]
KEYNOTE-022, 2019 1.36 [0.29; 6.34]
1.35 [0.36 ; 5.03 ] CA184-024, 2011, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015, KEYNOTE-022, 2019 4 95% 1,317 moderate not evaluable TRAE (grade 3-4)detailed results CA184-024, 2011 11.25 [6.30; 20.10]
KEYNOTE-002 (10 mg/kg), 2015 0.54 [0.32; 0.91]
KEYNOTE-002 (2 mg/kg), 2015 0.44 [0.25; 0.76]
KEYNOTE-022, 2019 3.60 [1.67; 7.74]
1.75 [0.36 ; 8.49 ] CA184-024, 2011, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015, KEYNOTE-022, 2019 4 96% 1,317 moderate not evaluable TRAE leading to death (grade 5)detailed results KEYNOTE-002 (10 mg/kg), 2015 1.92 [0.06; 57.48]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
KEYNOTE-022, 2019 2.02 [0.07; 61.28]
1.62 [0.21 ; 12.60 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015, KEYNOTE-022, 2019 3 0% 819 moderate not evaluable TRAE leading to discontinuation (any grade)detailed results KEYNOTE-002 (10 mg/kg), 2015 1.65 [0.70; 3.87]
KEYNOTE-002 (2 mg/kg), 2015 0.85 [0.32; 2.25]
KEYNOTE-022, 2019 2.67 [1.18; 6.03]
1.62 [0.86 ; 3.05 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015, KEYNOTE-022, 2019 3 36% 819 moderate not evaluable TRAE leading to discontinuation (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 2.73 [0.85; 8.76]
KEYNOTE-002 (2 mg/kg), 2015 1.46 [0.40; 5.25]
2.06 [0.87 ; 4.87 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Alopecia TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
0.96 [0.06 ; 15.38 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Anaemia TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.05 [0.00; 0.88]
KEYNOTE-002 (2 mg/kg), 2015 0.10 [0.01; 0.81]
0.08 [0.01 ; 0.43 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Arthralgia TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.06; 15.39]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.06; 15.48]
0.96 [0.13 ; 6.84 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Asthenia TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.06; 15.39]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.06; 15.48]
0.96 [0.13 ; 6.84 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Colitis TRAE (grade 3-4)detailed results CA184-024, 2011 10.35 [0.56; 190.49]
KEYNOTE-002 (10 mg/kg), 2015 2.90 [0.30; 28.13]
KEYNOTE-002 (2 mg/kg), 2015 0.48 [0.02; 14.37]
2.86 [0.59 ; 13.95 ] CA184-024, 2011, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,197 moderate not evaluable Constipation TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
0.96 [0.06 ; 15.38 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Decreased appetite TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
0.96 [0.06 ; 15.38 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Diarrhoea TRAE (grade 3-4)detailed results CA184-024, 2011 21.14 [1.23; 363.94]
KEYNOTE-002 (10 mg/kg), 2015 1.28 [0.28; 5.81]
KEYNOTE-002 (2 mg/kg), 2015 0.16 [0.01; 3.17]
1.62 [0.16 ; 16.38 ] CA184-024, 2011, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 64% 1,197 moderate not evaluable Dry skin TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
0.96 [0.06 ; 15.38 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Fatigue TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.23 [0.05; 1.10]
KEYNOTE-002 (2 mg/kg), 2015 0.23 [0.05; 1.11]
0.23 [0.08 ; 0.70 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Hepatitis TRAE (grade 3-4)detailed results CA184-024, 2011 8.25 [0.43; 156.83]
KEYNOTE-002 (10 mg/kg), 2015 3.85 [0.17; 86.06]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
3.82 [0.58 ; 24.96 ] CA184-024, 2011, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,197 moderate not evaluable Hyperthyroidism TRAE (grade 3-4)detailed results CA184-024, 2011 1.02 [0.02; 51.42]
KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
0.98 [0.10 ; 9.42 ] CA184-024, 2011, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,197 moderate not evaluable Hypophysitis TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 1.93 [0.06; 57.80]
1.43 [0.11 ; 18.64 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Hypothyroidism TRAE (grade 3-4)detailed results CA184-024, 2011 1.02 [0.02; 51.42]
KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
0.98 [0.10 ; 9.42 ] CA184-024, 2011, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,197 moderate not evaluable Increase AST TRAE (grade 3-4)detailed results CA184-024, 2011 52.70 [7.19; 385.99]
52.70 [7.19 ; 385.99 ] CA184-024, 2011 1 0% 498 NA not evaluable Increased ALT TRAE (grade 3-4)detailed results CA184-024, 2011 32.40 [7.79; 134.72]
32.40 [7.79 ; 134.72 ] CA184-024, 2011 1 0% 498 NA not evaluable Leucopenia TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.07 [0.00; 1.17]
KEYNOTE-002 (2 mg/kg), 2015 0.07 [0.00; 1.17]
0.07 [0.01 ; 0.50 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Maculopapular rash TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 1.92 [0.06; 57.48]
KEYNOTE-002 (2 mg/kg), 2015 1.93 [0.06; 57.80]
1.92 [0.17 ; 21.29 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Myalgia TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.48 [0.02; 14.29]
KEYNOTE-002 (2 mg/kg), 2015 1.93 [0.17; 21.50]
1.21 [0.17 ; 8.64 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Nausea TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.23 [0.03; 2.12]
KEYNOTE-002 (2 mg/kg), 2015 0.12 [0.01; 2.24]
0.18 [0.03 ; 1.07 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Neutropenia TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.08 [0.00; 1.39]
KEYNOTE-002 (2 mg/kg), 2015 0.08 [0.00; 1.40]
0.08 [0.01 ; 0.60 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Pancreatitis TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 1.92 [0.06; 57.48]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
1.42 [0.11 ; 18.63 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Paraesthesia TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
0.96 [0.06 ; 15.38 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Peripheral neuropathy TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.24 [0.01; 5.29]
KEYNOTE-002 (2 mg/kg), 2015 0.24 [0.01; 5.32]
0.24 [0.03 ; 2.13 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Pneumonitis TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 5.81 [0.29; 116.90]
KEYNOTE-002 (2 mg/kg), 2015 1.93 [0.06; 57.80]
3.58 [0.38 ; 34.02 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Pruritus TRAE (grade 3-4)detailed results CA184-024, 2011 10.35 [0.56; 190.49]
KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
2.97 [0.40 ; 22.18 ] CA184-024, 2011, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,197 moderate not evaluable Rash TRAE (grade 3-4)detailed results CA184-024, 2011 6.16 [0.31; 123.62]
KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
2.26 [0.29 ; 17.34 ] CA184-024, 2011, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,197 moderate not evaluable Thrombocytopenia TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.23 [0.03; 2.12]
KEYNOTE-002 (2 mg/kg), 2015 0.12 [0.01; 2.24]
0.18 [0.03 ; 1.07 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Thyroiditis TRAE (grade 3-4)detailed results CA184-024, 2011 1.02 [0.02; 51.42]
1.02 [0.02 ; 51.42 ] CA184-024, 2011 1 0% 498 NA not evaluable Uveitis TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 1.92 [0.06; 57.48]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
1.42 [0.11 ; 18.63 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Vitiligo TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
0.96 [0.06 ; 15.38 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Vomiting TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.23 [0.03; 2.12]
KEYNOTE-002 (2 mg/kg), 2015 0.24 [0.03; 2.13]
0.24 [0.05 ; 1.12 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Abdominal pain AE (grade 3-4)detailed results CA184-024, 2011 0.43 [0.11; 1.68]
0.43 [0.11 ; 1.68 ] CA184-024, 2011 1 0% 498 NA not evaluable Asthenia AE (grade 3-4)detailed results CA184-024, 2011 0.17 [0.02; 1.39]
0.17 [0.02 ; 1.39 ] CA184-024, 2011 1 0% 498 NA not evaluable Chills AE (grade 3-4)detailed results CA184-024, 2011 1.02 [0.02; 51.42]
1.02 [0.02 ; 51.42 ] CA184-024, 2011 1 0% 498 NA not evaluable Constipation AE (grade 3-4)detailed results CA184-024, 2011 1.02 [0.02; 51.42]
1.02 [0.02 ; 51.42 ] CA184-024, 2011 1 0% 498 NA not evaluable Cough AE (grade 3-4)detailed results CA184-024, 2011 2.04 [0.07; 60.99]
2.04 [0.07 ; 60.99 ] CA184-024, 2011 1 0% 498 NA not evaluable Decreased appetite AE (grade 3-4)detailed results CA184-024, 2011 0.76 [0.17; 3.43]
0.76 [0.17 ; 3.43 ] CA184-024, 2011 1 0% 498 NA not evaluable Diarrhoea AE (grade 3-4)detailed results CA184-024, 2011 21.14 [1.23; 363.94]
21.14 [1.23 ; 363.94 ] CA184-024, 2011 1 0% 498 NA not evaluable Dyspnoea AE (grade 3-4)detailed results CA184-024, 2011 16.77 [0.96; 293.61]
16.77 [0.96 ; 293.61 ] CA184-024, 2011 1 0% 498 NA not evaluable Fatigue AE (grade 3-4)detailed results CA184-024, 2011 2.44 [1.21; 4.94]
2.44 [1.21 ; 4.94 ] CA184-024, 2011 1 0% 498 NA not evaluable Headache AE (grade 3-4)detailed results CA184-024, 2011 4.12 [0.46; 37.08]
4.12 [0.46 ; 37.08 ] CA184-024, 2011 1 0% 498 NA not evaluable Increase AST AE (grade 3-4)detailed results CA184-024, 2011 18.42 [5.64; 60.14]
18.42 [5.64 ; 60.14 ] CA184-024, 2011 1 0% 498 NA not evaluable Increased ALT AE (grade 3-4)detailed results CA184-024, 2011 34.83 [8.39; 144.67]
34.83 [8.39 ; 144.67 ] CA184-024, 2011 1 0% 498 NA not evaluable Nausea AE (grade 3-4)detailed results CA184-024, 2011 1.36 [0.30; 6.14]
1.36 [0.30 ; 6.14 ] CA184-024, 2011 1 0% 498 NA not evaluable Pruritus AE (grade 3-4)detailed results CA184-024, 2011 10.35 [0.56; 190.49]
10.35 [0.56 ; 190.49 ] CA184-024, 2011 1 0% 498 NA not evaluable Pyrexia AE (grade 3-4)detailed results CA184-024, 2011 1.02 [0.02; 51.42]
1.02 [0.02 ; 51.42 ] CA184-024, 2011 1 0% 498 NA not evaluable Rash AE (grade 3-4)detailed results CA184-024, 2011 6.16 [0.31; 123.62]
6.16 [0.31 ; 123.62 ] CA184-024, 2011 1 0% 498 NA not evaluable Vomiting AE (grade 3-4)detailed results CA184-024, 2011 2.07 [0.61; 6.95]
2.07 [0.61 ; 6.95 ] CA184-024, 2011 1 0% 498 NA not evaluable Weight decreased AE (grade 3-4)detailed results CA184-024, 2011 1.02 [0.06; 16.34]
1.02 [0.06 ; 16.34 ] CA184-024, 2011 1 0% 498 NA not evaluable 0.0 100.0 1.0 relative treatment effect www.metaEvidence.org 2024-06-26 11:45 +02:00
TE: relative treatment effect (measured by a risk ratio, an odds ratio or an hazard ratio depending on what is reported in the papers);
k: number of studies; n: total number of patients;
ROB: risk of bias (ROB 2.0); Pub. bias: publication bias; OBS: observational studies; RCT: randomized clinical trials
pathologies: 286,69,129
- treatments: 204,504,850,329,558,579,549,868,502,741,556,812,813,367,851,361,602,1070,671,865,744,696,1083,1281,1282,1283,1082,866,852,417,603,1051,876,853,1018,661,673,1049,1440,854,374,1073,953,672,1080,862,855,360,719,721,720,842,642,674,1085,863,503,847,982,359,575,577,576,869,1081,981,875,505,952,1021,1079,767,1071,1074,873,561,644,1251,1044,724,874,1043,1041,1042,940,1258,746,745,856,634,861,416,864,769,980,369,743
