anti-PD-(L)1 for COVID-19: living meta-analysis of clinical studies

mML - L2 - all population, anti-PD-(L)1 versus anti-CTLA-4, meta-analysis of study results

Outcome	Relative effect 95%CI	Trt. better when	I2	k (RCT/OBS)	Bayesian probability	Overall ROB	Publication bias	Degree of certainty	Endpoint importance	Published MA
efficacy endpoints 00
deaths (OS)	0.66 [0.54, 0.80]	< 1	0%	2 studies (2/-)	100.0 %	some concern	not evaluable	moderate	crucial	-
deaths (OS) (extension)	0.68 [0.57, 0.81]	< 1	0%	2 studies (2/-)	100.0 %	some concern	not evaluable	moderate	important	-
PFS (extension)	0.61 [0.53, 0.70]	< 1	0%	2 studies (2/-)	100.0 %	some concern	not evaluable	moderate	important	-
progression or deaths (PFS)	0.58 [0.50, 0.68]	< 1	0%	2 studies (2/-)	100.0 %	some concern	not evaluable	moderate	important	-
objective responses (ORR)	3.70 [2.71, 5.06]	> 1	0%	2 studies (2/-)	100.0 %	some concern	not evaluable	moderate	non important	-
safety endpoints 00
STRAE (any grade)	0.65 [0.46, 0.92]	< 1	0%	2 studies (2/-)	99.3 %	some concern	not evaluable	moderate	non important	-
STRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
TRAE (any grade)	1.36 [0.98, 1.90]	< 1	25%	2 studies (2/-)	3.5 %	some concern	not evaluable	moderate	non important	-
TRAE (grade 3-4)	0.83 [0.61, 1.13]	< 1	0%	2 studies (2/-)	88.0 %	some concern	not evaluable	moderate	non important	-
TRAE leading to death (grade 5)	1.37 [0.11, 17.90]	< 1	0%	2 studies (2/-)	40.6 %	some concern	not evaluable	moderate	non important	-
TRAE leading to discontinuation (any grade)	0.97 [0.60, 1.60]	< 1	25%	2 studies (2/-)	54.1 %	some concern	not evaluable	moderate	non important	-
TRAE leading to discontinuation (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
TRAE (grade 3-4) endpoints 00
Abdominal pain TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Alopecia TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Anaemia TRAE (grade 3-4)	1.16 [0.16, 8.29]	< 1	0%	2 studies (2/-)	44.1 %	some concern	not evaluable	moderate	non important	-
Arthralgia TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Asthenia TRAE (grade 3-4)	0.35 [0.05, 2.37]	< 1	0%	2 studies (2/-)	85.7 %	some concern	not evaluable	moderate	non important	-
Chills TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Colitis TRAE (grade 3-4)	0.27 [0.14, 0.54]	< 1	0%	2 studies (2/-)	100.0 %	some concern	not evaluable	moderate	non important	-
Constipation TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Cough TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Decreased appetite TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Diabetes TRAE (grade 3-4)	1.85 [0.06, 55.43]	< 1	0%	1 study (1/-)	36.3 %	NA	not evaluable		non important	-
Diarrhoea TRAE (grade 3-4)	0.66 [0.29, 1.54]	< 1	0%	2 studies (2/-)	83.0 %	some concern	not evaluable	moderate	non important	-
Dry skin TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Dyspnoea TRAE (grade 3-4)	0.70 [0.08, 6.00]	< 1	0%	2 studies (2/-)	62.7 %	some concern	not evaluable	moderate	non important	-
Fatigue TRAE (grade 3-4)	0.64 [0.17, 2.37]	< 1	0%	2 studies (2/-)	74.9 %	some concern	not evaluable	moderate	non important	-
Headache TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Hepatitis TRAE (grade 3-4)	3.66 [0.77, 17.46]	< 1	0%	2 studies (2/-)	5.2 %	some concern	not evaluable	moderate	non important	-
Hyperthyroidism TRAE (grade 3-4)	0.46 [0.04, 5.09]	< 1	0%	2 studies (2/-)	73.5 %	some concern	not evaluable	moderate	non important	-
Hypophysitis TRAE (grade 3-4)	0.35 [0.05, 2.37]	< 1	0%	2 studies (2/-)	85.7 %	some concern	not evaluable	moderate	non important	-
Hypothyroidism TRAE (grade 3-4)	1.37 [0.11, 17.90]	< 1	0%	2 studies (2/-)	40.6 %	some concern	not evaluable	moderate	non important	-
Increase AST TRAE (grade 3-4)	0.35 [0.05, 2.37]	< 1	0%	2 studies (2/-)	85.7 %	some concern	not evaluable	moderate	non important	-
Increased ALT TRAE (grade 3-4)	0.35 [0.05, 2.37]	< 1	0%	2 studies (2/-)	85.7 %	some concern	not evaluable	moderate	non important	-
Maculopapular rash TRAE (grade 3-4)	0.70 [0.08, 6.00]	< 1	0%	2 studies (2/-)	62.7 %	some concern	not evaluable	moderate	non important	-
Myalgia TRAE (grade 3-4)	0.70 [0.08, 6.00]	< 1	0%	2 studies (2/-)	62.8 %	some concern	not evaluable	moderate	non important	-
Myositis TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Nausea TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Nephritis TRAE (grade 3-4)	0.46 [0.04, 5.09]	< 1	0%	2 studies (2/-)	73.5 %	some concern	not evaluable	moderate	non important	-
Neutropenia TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Paraesthesia TRAE (grade 3-4)	0.46 [0.04, 5.09]	< 1	0%	2 studies (2/-)	73.5 %	some concern	not evaluable	moderate	non important	-
Pneumonitis TRAE (grade 3-4)	0.70 [0.08, 6.00]	< 1	0%	2 studies (2/-)	62.7 %	some concern	not evaluable	moderate	non important	-
Pruritic rash TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Pruritus TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Pyrexia TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Rash TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Uveitis TRAE (grade 3-4)	0.92 [0.06, 14.79]	< 1	0%	2 studies (2/-)	52.3 %	some concern	not evaluable	moderate	non important	-
Vomiting TRAE (grade 3-4)	1.37 [0.11, 17.90]	< 1	0%	2 studies (2/-)	40.6 %	some concern	not evaluable	moderate	non important	-
Weight decreased TRAE (grade 3-4)	0.46 [0.04, 5.09]	< 1	0%	2 studies (2/-)	73.5 %	some concern	not evaluable	moderate	non important	-

LoD: level of statistical demonstration: Statistically conclusive: statistically significant with a strict control of overall risk of type 1 error (statistically demonstrated), does not take into account the risk of bias; suggested: nominally statistically significant but without a strict control of overall risk of type 1 error; inconclusive: not nominally statistically significant; safety concerns;
Bayesian probability: Bayesian posterior probability of treatment effect (computed with a noninformative prior); ROB: risk of bias; k: number of studies; published MA: number of published meta-analysis on the same topic; degree of certainty adapted from GRADE. Trt. better when: indicates when the relative treatment effect shows that the studied treatment is better than control.

mML - L2 - all population, anti-PD-(L)1 versus anti-CTLA-4, meta-analysis of study results

efficacy endpoints 00

safety endpoints 00

TRAE (grade 3-4) endpoints 00