somewordstoolate/Q2CRBench-3 huggingface dataset:
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: Abatacept
Outcome: Serious adverse events (1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious imprecision. Confidence interval includes both values suggesting benefit and values suggesting harm. Small sample size.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: ABA: 14/116 (12.1%)
MTX monotherapy: 9/116 (7.8%)
Effect: Relative Effect (95% CI): RR 1.56 (0.70 to 3.45)
Absolute Effect (95% CI): 43 more per 1,000 (from 23 fewer to 190 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: Abatacept
Outcome: Withdrawal due to adverse events (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious imprecision. Confidence interval includes both values suggesting benefit and values suggesting harm. Small sample size.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: ABA: 8/116 (6.9%)
MTX monotherapy: 5/116 (4.3%)
Effect: Relative Effect (95% CI): RR 1.60 (0.54 to 4.75)
Absolute Effect (95% CI): 26 more per 1,000 (from 20 fewer to 162 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: Abatacept
Outcome: Withdrawal due to lack of efficacy (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious imprecision. Confidence interval includes both values suggesting benefit and values suggesting harm. Small sample size.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: ABA: 6/116 (5.2%)
MTX monotherapy: 11/116 (9.5%)
Effect: Relative Effect (95% CI): RR 0.55 (0.21 to 1.43)
Absolute Effect (95% CI): 43 fewer per 1,000 (from 75 fewer to 41 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: Abatacept
Outcome: Death (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious imprecision. Small sample size and very low number of events.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: ABA: 0/116 (0.0%)
MTX monotherapy: 0/116 (0.0%)
Effect: Relative Effect (95% CI): not estimable
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: Abatacept
Outcome: Malignancy (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious imprecision. Small sample size and very low number of events.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: ABA: 2/116 (1.7%)
MTX monotherapy: 1/116 (0.9%)
Effect: Relative Effect (95% CI): RR 2.00 (0.18 to 21.75)
Absolute Effect (95% CI): 9 more per 1,000 (from 7 fewer to 179 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: Abatacept
Outcome: Malignancy (from SR of harms) ABA vs MTX

Evidence assessment:
GRADE: result_interpretation: The Systematic Review RefID=1220, 2017 (RCTs=4, n=Not provided) comparing Abatacept vs Placebo + csDMARD among RA and showed that for Cancer, the result was Peto OR=1.12 (0.33, 3.81)
Study design: Systematic Review
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: IL-6 Receptor Inhibitor
Outcome: Disease activity (follow up: 1 year; assessed with: ACR 20)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population exposed to non-MTX csDMARDs.
Imprecision: result: SERIOUS
rationales: Downgraded by one level due to serious imprecision. Confidence interval includes both values suggesting no effect and values suggesting benefit.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: IL-6i: 184/292 (63.0%)
MTX monotherapy: 164/287 (57.1%)
Effect: Relative Effect (95% CI): RR 1.10 (0.97 to 1.26)
Absolute Effect (95% CI): 57 more per 1,000 (from 17 fewer to 149 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: IL-6 Receptor Inhibitor
Outcome: Disease activity (follow up: 1 year; assessed with: ACR 50)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population exposed to non-MTX csDMARDs.
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: IL-6i: 145/292 (49.7%)
MTX monotherapy: 117/287 (40.8%)
Effect: Relative Effect (95% CI): RR 1.22 (1.02 to 1.46)
Absolute Effect (95% CI): 90 more per 1,000 (from 8 more to 188 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: IL-6 Receptor Inhibitor
Outcome: Disease activity (follow up: 1 year; assessed with: ACR 70)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population exposed to non-MTX csDMARDs.
Imprecision: result: SERIOUS
rationales: Downgraded by one level due to serious imprecision. Confidence interval includes both values suggesting no effect and values suggesting benefit.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: IL-6i: 107/292 (36.6%)
MTX monotherapy: 84/287 (29.3%)
Effect: Relative Effect (95% CI): RR 1.25 (0.99 to 1.58)
Absolute Effect (95% CI): 73 more per 1,000 (from 3 fewer to 170 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: IL-6 Receptor Inhibitor
Outcome: Disease activity (follow up: 1 year; assessed with: DAS28-ESR (Lower values –> benefit) (MCID -1.17)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population exposed to non-MTX csDMARDs.
Imprecision: result: SERIOUS
rationales: Downgraded by one level due to serious imprecision. Confidence interval includes both values suggesting no effect and values suggesting benefit.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: IL-6i: 292
MTX monotherapy: 287
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 0.96 lower (1.24 lower to 0.68 lower)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: IL-6 Receptor Inhibitor
Outcome: Remission (follow up: 1 year; assessed with: DAS28-ESR <2.6)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population exposed to non-MTX csDMARDs.
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: IL-6i: 115/292 (39.4%)
MTX monotherapy: 56/287 (19.5%)
Effect: Relative Effect (95% CI): RR 2.02 (1.53 to 2.66)
Absolute Effect (95% CI): 199 more per 1,000 (from 103 more to 324 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: IL-6 Receptor Inhibitor
Outcome: Radiographic progression (follow up: 1 year; assessed with: mTSS (Lower values –> benefit) (MCID 4.6)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population exposed to non-MTX csDMARDs.
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: IL-6i: 275
MTX monotherapy: 267
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 0.88 lower (1.44 lower to 0.32 lower)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: IL-6 Receptor Inhibitor
Outcome: Disability (follow up: 1 year; assessed with: HAQ-DI (Lower values – > benefit) (MCID -0.22)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population exposed to non-MTX csDMARDs.
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: IL-6i: 0
MTX monotherapy: 0
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 0.03 lower (0.15 lower to 0.09 higher)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: IL-6 Receptor Inhibitor
Outcome: Quality of life (follow up: 1 year; assessed with: SF-36 PCS (Higher values – > benefit) (MCID 4.4)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population exposed to non-MTX csDMARDs.
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: IL-6i: 0
MTX monotherapy: 0
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 0.14 higher (0.13 lower to 0.41 higher)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: IL-6 Receptor Inhibitor
Outcome: Quality of life (1 year) (follow up: 1 year; assessed with: SF-36 MCS (Higher values – > benefit) (MCID 3.1)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population exposed to non-MTX csDMARDs.
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: IL-6i: 0
MTX monotherapy: 0
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 0.34 higher (0.68 lower to 1.36 higher)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: IL-6 Receptor Inhibitor
Outcome: Serious adverse events (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population exposed to non-MTX csDMARDs.
Imprecision: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious imprecision. Confidence interval includes both values suggesting benefit and values suggesting harm.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: IL-6i: 25/292(8.6%)
MTX monotherapy: 24/282 (8.5%)
Effect: Relative Effect (95% CI): RR 1.01 (0.59 to 1.72)
Absolute Effect (95% CI): 1 more per 1,000 (from 35 fewer to 61 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: IL-6 Receptor Inhibitor
Outcome: Withdrawal due to lack of efficacy (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population exposed to non-MTX csDMARDs.
Imprecision: result: SERIOUS
rationales: Downgraded by one level due to serious imprecision. Confidence interval includes both values suggesting no effect and values suggesting harm.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: IL-6i: 34/292(11.6%)
MTX monotherapy: 21/282 (7.4%)
Effect: Relative Effect (95% CI): RR 1.56 (0.93 to 2.63)
Absolute Effect (95% CI): 42 more per 1,000 (from 5 fewer to 121 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: IL-6 Receptor Inhibitor
Outcome: Death (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population exposed to non-MTX csDMARDs.
Imprecision: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious imprecision. Confidence interval includes both values suggesting benefit and values suggesting harm.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: IL-6i: 1/292 (0.3%)
MTX monotherapy: 2/282 (0.7%)
Effect: Relative Effect (95% CI): RR 0.48 (0.04 to 5.30)
Absolute Effect (95% CI): 4 fewer per 1,000 (from 7 fewer to 30 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive MTX monotherapy or boDMARD monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: IL-6 Receptor Inhibitor
Outcome: Malignancy (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population exposed to non-MTX csDMARDs.
Imprecision: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious imprecision. Confidence interval includes both values suggesting benefit and values suggesting harm.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: IL-6i: 2/292 (0.7%)
MTX monotherapy: 3/282 (1.1%)
Effect: Relative Effect (95% CI): RR 0.64 (0.11 to 3.82)
Absolute Effect (95% CI): 4 fewer per 1,000 (from 9 fewer to 30 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio