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: IL-6 Receptor Inhibitor
Outcome: Myocardial infarction (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. Low number of events.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: IL-6i: 1/292 (0.3%)
MTX monotherapy: 0/282 (0.0%)
Effect: Relative Effect (95% CI): RR 2.90 (0.12 to 70.83)
Absolute Effect (95% CI): 0 fewer per 1,000 (from 0 fewer to 0 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 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 (from SRs of harms)

Evidence assessment:
GRADE: result_interpretation: The Systematic Review RefID=4638, 2012 (RCTs=1, n=302) comparing IL-6 Receptor Inhibitors vs Placebo + MTX among RA showed that for Cancer, the result was RR=6.5 (0.34-124.2) at 1 year and RR=0.33 (0.01-8.0) at 6 months (RCTs=2, n=697 at 6 months)
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: Serious adverse events (from SRs of harms)

Evidence assessment:
GRADE: result_interpretation: The systematic review RefID=18, 2018 (RCTs=2, n=785) comparing IL-6 inhibitors vs MTX among TCZ naïve RA patients showed that for serious adverse events, the result was RR=2.57 (95% 0.61-10.93, p=0.2).
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: JAK Inhibitor
Outcome: Disease activity (follow up: 2 years; assessed with: ACR 20)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
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: MODERATE
No of participants: JAKi (Tofa): 239/373 (64.1%)
MTX monotherapy: 79/186 (42.5%)
Effect: Relative Effect (95% CI): RR 1.51 (1.26 to 1.81)
Absolute Effect (95% CI): 217 more per 1,000 (from 110 more to 344 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: JAK Inhibitor
Outcome: Disease activity (follow up: 2 years; assessed with: ACR 50)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
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: MODERATE
No of participants: JAKi (Tofa): 184/373 (49.3%)
MTX monotherapy: 53/186 (28.5%)
Effect: Relative Effect (95% CI): RR 1.73 (1.35 to 2.22)
Absolute Effect (95% CI): 208 more per 1,000 (from 100 more to 348 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: JAK Inhibitor
Outcome: Disease activity (follow up: 2 years; assessed with: ACR 70)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
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: MODERATE
No of participants: JAKi (Tofa): 128/373 (34.3%)
MTX monotherapy: 28/186 (15.1%)
Effect: Relative Effect (95% CI): RR 2.28 (1.58 to 3.30)
Absolute Effect (95% CI): 193 more per 1,000 (from 87 more to 346 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: JAK Inhibitor
Outcome: Disease activity (follow up: 2 years; assessed with: DAS28-ESR (Lower values – > benefit) (MCID -1.17)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
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: MODERATE
No of participants: JAKi (Tofa): 373
MTX monotherapy: 186
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 0.6 lower (0.88 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: JAK Inhibitor
Outcome: Remission (follow up: 2 years; assessed with: DAS28-ESR < 2.6)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
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: MODERATE
No of participants: JAKi (Tofa): 78/373 (20.9%)
MTX monotherapy: 18/186 (9.7%)
Effect: Relative Effect (95% CI): RR 2.16 (1.34 to 3.50)
Absolute Effect (95% CI): 112 more per 1,000 (from 33 more to 242 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: JAK Inhibitor
Outcome: Radiographic progression (follow up: 2 years; assessed with: mTSS (Lower values – > benefit) (MCID 4.6)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
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: MODERATE
No of participants: JAKi (Tofa): 373
MTX monotherapy: 186
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 1.53 lower (2.36 lower to 0.7 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: JAK Inhibitor
Outcome: Disability (follow up: 2 years; assessed with: HAQ-DI (Lower values – > benefit) (MCID -0.22)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
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 benefit and values suggesting no effect.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: JAKi (Tofa): 373
MTX monotherapy: 186
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 0.2 lower (0.31 lower to 0.09 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: JAK Inhibitor
Outcome: Serious adverse events (follow up: 2 years)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
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: JAKi (Tofa): 40/373 (10.7%)
MTX monotherapy: 22/186 (11.8%)
Effect: Relative Effect (95% CI): RR 0.91 (0.56 to 1.48)
Absolute Effect (95% CI): 11 fewer per 1,000 (from 52 fewer to 57 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: JAK Inhibitor
Outcome: Withdrawal due to adverse events (follow up: 2 years)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
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: JAKi (Tofa): 40/373 (10.7%)
MTX monotherapy: 25/186 (13.4%)
Effect: Relative Effect (95% CI): RR 0.80 (0.50 to 1.27)
Absolute Effect (95% CI): 27 fewer per 1,000 (from 67 fewer to 36 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: JAK Inhibitor
Outcome: Death (follow up: 2 years)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
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. Very low number of events.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: JAKi (Tofa): 3/373 (0.8%)
MTX monotherapy: 0/186 (0.0%)
Effect: Relative Effect (95% CI): RR 3.50 (0.18 to 67.41)
Absolute Effect (95% CI): 0 fewer per 1,000 (from 0 fewer to 0 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 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: JAK Inhibitor
Outcome: Malignancy (follow up: 2 years)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
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 one level due to serious imprecision. Confidence interval includes both values suggesting benefit and values suggesting no effect.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: JAKi (Tofa): 2/373 (0.5%)
MTX monotherapy: 1/186 (0.5%)
Effect: Relative Effect (95% CI): RR 1.00 (0.09 to 10.93)
Absolute Effect (95% CI): 0 fewer per 1,000 (from 5 fewer to 53 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: JAK Inhibitor
Outcome: Malignancy (from SRs on harms)

Evidence assessment:
GRADE: result_interpretation: The systematic review RefID=1220, 2017 (RCTs=3) comparing tofacitinib 5mg vs placebo + csDMARD among RA showed that for cancer, the result was Peto OR=2.39 (0.50, 11.50)
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 monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor
Outcome: Disease activity (follow up: 2 years; 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: SERIOUS
rationales: Downgraded by one level due to serious inconsistency. Unexplained heterogeneity I2=65%.
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.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: TNFi: 207/467 (44.3%)
MTX monotherapy: 205/459 (44.7%)
Effect: Relative Effect (95% CI): RR 0.99 (0.86 to 1.15)
Absolute Effect (95% CI): 4 fewer per 1,000 (from 63 fewer to 67 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 monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor
Outcome: Disease activity (follow up: 2 years; 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: SERIOUS
rationales: Downgraded by one level due to serious inconsistency. Unexplained heterogeneity I2=75%.
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.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: TNFi: 188/451 (41.7%)
MTX monotherapy: 182/426 (42.7%)
Effect: Relative Effect (95% CI): RR 0.98 (0.84 to 1.14)
Absolute Effect (95% CI): 9 fewer per 1,000 (from 68 fewer to 60 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 monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor
Outcome: Disease activity (follow up: 2 years; 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: 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.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: TNFi: 128/451 (28.4%)
MTX monotherapy: 113/426 (26.5%)
Effect: Relative Effect (95% CI): RR 1.07 (0.86 to 1.33)
Absolute Effect (95% CI): 19 more per 1,000 (from 37 fewer to 88 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 monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor
Outcome: Remission (follow up: 2 years; 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: 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.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: TNFi: 69/274 (25.2%)
MTX monotherapy: 64/257 (24.9%)
Effect: Relative Effect (95% CI): RR 1.01 (0.75 to 1.36)
Absolute Effect (95% CI): 2 more per 1,000 (from 62 fewer to 90 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 monotherapy or tsDMARD monotherapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and moderate to high disease activity
Intervention: MTX monotherapy
Comparator: TNF Inhibitor
Outcome: Radiographic progression (follow up: 2 years; 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: NOT_SERIOUS
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: MODERATE
No of participants: TNFi: 177
MTX monotherapy: 169
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 1.9 lower (3.19 lower to 0.61 lower)(The study PREMIER found that the RR of developing no radiographic progression (change in mTSS ≤0.5) was 1.33 (95%CI 1.07 to 1.65), absolute risk increase 112 more per 1000 (95%CI 24 more to 220 more).)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio