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 with MTX or tsDMARD with MTX?
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 + MTX
Outcome: Quality of Life (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: Rated down by one level for 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 non-MTX csDMARD exposed population.
Imprecision: result: SERIOUS
rationales: Rated down by one level for imprecision as the CI 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: TCZ+MTX: 0
MTX monotherapy: 0
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 1.25 higher (1.58 lower to 4.08 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 with MTX or tsDMARD with MTX?
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 + MTX
Outcome: Withdrawal due to adverse events (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Rated down by one level for 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 non-MTX csDMARD exposed population.
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: TCZ+MTX: 94/579 (16.2%)
MTX monotherapy: 21/282 (7.4%)
Effect: Relative Effect (95% CI): RR 2.18 (1.39 to 3.42)
Absolute Effect (95% CI): 88 more per 1,000 (from 29 more to 180 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 with MTX or tsDMARD with MTX?
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 + MTX
Outcome: Serious adverse events (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Rated down by one level for 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 non-MTX csDMARD exposed population.
Imprecision: result: SERIOUS
rationales: Rated down by one level for imprecision as the CI 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: TCZ+MTX: 60/579 (10.4%)
MTX monotherapy: 24/282 (8.5%)
Effect: Relative Effect (95% CI): RR 1.22 (0.78 to 1.91)
Absolute Effect (95% CI): 19 more per 1,000 (from 19 fewer to 77 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 with MTX or tsDMARD with MTX?
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 + MTX
Outcome: Malignancy (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Rated down by one level for 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 non-MTX csDMARD exposed population.
Imprecision: result: SERIOUS
rationales: Rated down by one level for imprecision as the CI 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: TCZ+MTX: 5/579 (0.9%)
MTX monotherapy: 3/282 (1.1%)
Effect: Relative Effect (95% CI): RR 0.81 (0.20 to 3.37)
Absolute Effect (95% CI): 2 fewer per 1,000 (from 9 fewer to 25 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 with MTX or tsDMARD with MTX?
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 + MTX
Outcome: Myocardial infarction (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Rated down by one level for 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 non-MTX csDMARD exposed population.
Imprecision: result: VERY_SERIOUS
rationales: Rated down by two levels for imprecision as the CI includes both values suggesting benefit and values suggesting harm
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: TCZ+MTX: 4/579 (0.7%)
MTX monotherapy: 0/282 (0.0%)
Effect: Relative Effect (95% CI): RR 4.39 (0.24 to 81.28)
Absolute Effect (95% CI): 7 fewer per 1,000 (from 480 fewer to 160 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 with MTX or tsDMARD with MTX?
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 + MTX
Outcome: Death (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Rated down by one level for 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 non-MTX csDMARD exposed population.
Imprecision: result: SERIOUS
rationales: Rated down by one level for imprecision as the CI 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: TCZ+MTX: 6/579 (1.0%)
MTX monotherapy: 2/282 (0.7%)
Effect: Relative Effect (95% CI): RR 1.46 (0.30 to 7.19)
Absolute Effect (95% CI): 3 more per 1,000 (from 5 fewer to 44 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 with MTX or tsDMARD with MTX?
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 + MTX
Outcome: Serious adverse events (from SRs on harms)

Evidence assessment:
GRADE: result_interpretation: The Systematic Review RefID=5712, 2011 (RCTs=4, n=2701) comparing Tocilizumab + MTX vs Placebo + MTX among MTX naïve RA showed that for Serious adverse events, the result was OR=0.78 (0.45, 1.33) 
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 with MTX or tsDMARD with MTX?
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 + MTX
Outcome: Malignancy (from SRs on harms)

Evidence assessment:
GRADE: result_interpretation: The Systematic Review RefID=4638, 2012 (RCTs=1, n=1190) comparing Tocilizumab + MTX vs Placebo + MTX among RA showed that for Cancer, the result was RR=4.4 (0.56-34.8) at 1 year and RR=0.41 (0.14-1.2) at 6 months (RCT=4, n=2950) 
Study design: Systematic Review
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity receive MTX monotherapy or boDMARD with MTX or tsDMARD with MTX?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor + MTX
Outcome: Disease activity (follow up: range 6 months to 2 years; assessed with: ACR 20)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: HIGH
No of participants: TNFi+MTX: 1414/2051 (68.9%)
MTX monotherapy: 1134/2094 (54.2%)
Effect: Relative Effect (95% CI): RR 1.25 (1.19 to 1.31)
Absolute Effect (95% CI): 135 more per 1,000 (from 103 more to 168 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 exposed RA and moderate to high disease activity receive MTX monotherapy or boDMARD with MTX or tsDMARD with MTX?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor + MTX
Outcome: Disease activity (follow up: 1 year; assessed with: ACR 50)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: HIGH
No of participants: TNFi+MTX: 559/974 (57.4%)
MTX monotherapy: 363/881 (41.2%)
Effect: Relative Effect (95% CI): RR 1.42 (1.29 to 1.56)
Absolute Effect (95% CI): 173 more per 1,000 (from 119 more to 231 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 exposed RA and moderate to high disease activity receive MTX monotherapy or boDMARD with MTX or tsDMARD with MTX?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor + MTX
Outcome: Disease activity (follow up: range 6 months to 2 years; assessed with: ACR 70)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
rationales: I2=17%
Indirectness: result: NOT_SERIOUS
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: HIGH
No of participants: TNFi+MTX: 733/2051 (35.7%)
MTX monotherapy: 401/2094 (19.1%)
Effect: Relative Effect (95% CI): RR 1.74 (1.55 to 1.96)
Absolute Effect (95% CI): 142 more per 1,000 (from 105 more to 184 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 exposed RA and moderate to high disease activity receive MTX monotherapy or boDMARD with MTX or tsDMARD with MTX?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor + MTX
Outcome: Disease activity (follow up: range 6 months to 1 year; assessed with: DAS28-ESR/CRP)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
rationales: According to the Cochrane's handbook, Cohen suggested that SMD=0.2 be considered a 'small' effect size, 0.5 represents a 'medium' effect size and 0.8 a 'large' effect size. This means that if two groups' means do not differ by 0.2 standard deviations or more, the difference is trivial, even if it is statistically significant.
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: HIGH
No of participants: TNFi+MTX: 1133
MTX monotherapy: 1200
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): SMD 0.39 lower (0.47 lower to 0.31 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 exposed RA and moderate to high disease activity receive MTX monotherapy or boDMARD with MTX or tsDMARD with MTX?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor + MTX
Outcome: Remission (follow up: range 6 months to 2 years; assessed with: DAS28-ESR remission <2.6)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: HIGH
No of participants: TNFi+MTX: 662/1743 (38.0%)
MTX monotherapy: 353/1667 (21.2%)
Effect: Relative Effect (95% CI): RR 1.80 (1.62 to 2.01)
Absolute Effect (95% CI): 169 more per 1,000 (from 131 more to 214 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 exposed RA and moderate to high disease activity receive MTX monotherapy or boDMARD with MTX or tsDMARD with MTX?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor + MTX
Outcome: Radiographic progression (follow up: range 6 months to 1 year; assessed with: mTSS)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious inconsistency. I2=90%.
Indirectness: result: NOT_SERIOUS
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: TNFi+MTX: 782
MTX monotherapy: 702
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 1.94 lower (3.61 lower to 0.28 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 exposed RA and moderate to high disease activity receive MTX monotherapy or boDMARD with MTX or tsDMARD with MTX?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor + MTX
Outcome: Fatigue (follow up: range 1 year to 2 years; assessed with: VAS-F or FACIT-F)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: SERIOUS
rationales: I2=55%
Indirectness: result: NOT_SERIOUS
Imprecision: result: SERIOUS
rationales: Rated down by one level for imprecision, as CI includes both values suggesting benefits and values suggesting no effect. According to the Cochrane's handbook, Cohen suggested that SMD=0.2 be considered a 'small' effect size, 0.5 represents a 'medium' effect size and 0.8 a 'large' effect size. This means that if two groups' means do not differ by 0.2 standard deviations or more, the difference is trivial, even if it is statistically significant.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: TNFi+MTX: 530
MTX monotherapy: 520
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): SMD 0.15 higher (0.03 higher to 0.28 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 exposed RA and moderate to high disease activity receive MTX monotherapy or boDMARD with MTX or tsDMARD with MTX?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor + MTX
Outcome: Pain (follow up: range 1 year to 2 years; assessed with: VAS pain (0-100))
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious inconsistency. I2=85%
Indirectness: result: NOT_SERIOUS
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: TNFi+MTX: 530
MTX monotherapy: 519
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 4.66 lower (6.93 lower to 2.39 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 exposed RA and moderate to high disease activity receive MTX monotherapy or boDMARD with MTX or tsDMARD with MTX?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor + MTX
Outcome: Disability (follow up: range 6 months to 24 months; assessed with: HAQ-DI)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious inconsistency. I2=92%
Indirectness: result: NOT_SERIOUS
Imprecision: result: SERIOUS
rationales: Rated down by one level for imprecision, as CI includes both values suggesting benefits and values suggesting no effect. According to the Cochrane's handbook, Cohen suggested that SMD=0.2 be considered a 'small' effect size, 0.5 represents a 'medium' effect size and 0.8 a 'large' effect size. This means that if two groups' means do not differ by 0.2 standard deviations or more, the difference is trivial, even if it is statistically significant.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: TNFi+MTX: 1135
MTX monotherapy: 1119
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 0.19 lower (0.25 lower to 0.14 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 exposed RA and moderate to high disease activity receive MTX monotherapy or boDMARD with MTX or tsDMARD with MTX?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor + MTX
Outcome: Quality of life (follow up: range 1 year to 2 years; assessed with: SF-36 PCS)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: SERIOUS
rationales: Downgraded by two levels due to very serious inconsistency. I2=88%
Indirectness: result: NOT_SERIOUS
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: MODERATE
No of participants: TNFi+MTX: 880
MTX monotherapy: 792
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 1.39 higher (1.42 lower to 4.2 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 exposed RA and moderate to high disease activity receive MTX monotherapy or boDMARD with MTX or tsDMARD with MTX?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor + MTX
Outcome: Quality of life (follow up: range 1 year to 2 years; assessed with: SF-36 MCS)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: HIGH
No of participants: TNFi+MTX: 521
MTX monotherapy: 510
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 0.15 lower (1.35 lower to 1.04 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 exposed RA and moderate to high disease activity receive MTX monotherapy or boDMARD with MTX or tsDMARD with MTX?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor + MTX
Outcome: Withdrawal due to lack of efficacy (follow up: range 1 year to 2 years)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
rationales: I2=42%
Indirectness: result: NOT_SERIOUS
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: HIGH
No of participants: TNFi+MTX: 33/716 (4.6%)
MTX monotherapy: 99/628 (15.8%)
Effect: Relative Effect (95% CI): RR 0.32 (0.19 to 0.52)
Absolute Effect (95% CI): 107 fewer per 1,000 (from 128 fewer to 76 fewer)
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 exposed RA and moderate to high disease activity receive MTX monotherapy or boDMARD with MTX or tsDMARD with MTX?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor + MTX
Outcome: Withdrawal due to adverse events (follow up: range 6 months to 2 years)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: HIGH
No of participants: TNFi+MTX: 109/1389 (7.8%)
MTX monotherapy: 53/1305 (4.1%)
Effect: Relative Effect (95% CI): RR 1.88 (1.36 to 2.59)
Absolute Effect (95% CI): 36 more per 1,000 (from 15 more to 65 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio