Table 3.
Effect of bDMARDs on the change in mSASSS and on the likelihood of progression: comparative studies with variable exposure to treatment
| Study | Follow-up years | N patients/intervals* | Comparison | Outcome | Handling of pretreatment time-varying confounders | Time-varying mediator |
Total effect (95% CI) |
Mediation analysis |
| Molnar et al, 201744 | Up to 10 | 432/616 | TNFi versus no TNFi | ≥2 mSASSS | Adjust. (mSASSS, ASDAS and NSAID+baseline variables) | ASDAS (start interval) |
OR: 0.5 (0.3 to 0.9) | Indirect effect + Direct effect – |
| Gensler et al, 201842 | 4 | 519/NR | TNFi versus no TNFi† | mSASSS | Adjust. (ASDAS+baseline variables) Strat. (NSAID index) | NA | Δ: −3.3 (–4.0 to –2.6) | NA |
| Park et al, 201945 | NR | 215/518 | TNFi versus NSAID | mSASSS | No TV confounders. Adjust. BL (age, CRP, smoking and syndesmophytes) | CRP (aver interval) |
β: −0.9 (−1.5 to −0.3) | Indirect effect + Direct effect – |
| Koo et al, 202043 | Up to 18 | 338/2364 | TNFi on versus TNFi off | mSASSS | IPTW (mSASSS, ESR, CRP, BASDAI and comedication+baseline variables) | NA | β: −0.1 (–0.2 to 0.0) | NA |
| Sepriano et al, 202146 | Up to 10 | 314/442 | TNFi versus no TNFi | mSASSS | Adjust. (mSASSS)‡+PS. Adjust. BL (gender, symptom duration, ASDAS, HLA-B27, mSASSS, EMM and NSAIDs) | ASDAS (start interval) |
β: −0.8 (–1.4 to −0.2) | Indirect effect + Direct effect + |
Total effect: Effect of TNFi on radiographic progression at the end of each interval adjusting for pretreatment confounders but not for the mediator.
Direct effect: Effect of TNFi on radiographic progression at the end of each interval adjusting for pretreatment confounders and for the mediator.
Indirect effect: Effect of TNFi on radiographic progression at the end of each interval through the mediator (also adjusting for pretreatment confounders).
*2-year intervals in all studies.
†If NSAID index ≥50.
‡NSAIDs not kept in the final model because it did not prove to confound the association of interest.
adjust, adjustment; ASDAS, Ankylosing Spondylitis Disease Activity Score; aver, average; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; bDMARDs, biological disease-modifying antirheumatic drugs; BL, baseline; CRP, C reactive protein; EMM, extramusculoskeletal manifestations (uveitis, inflammatory bowel disease and psoriasis); ESR, erythrocyte sedimentation rate; HLA, human leukocyte antigen; IPTW, inverse probability treatment weighting; mSASSS, modified Stoke Ankylosing Spondylitis Spinal Score; NR, not reported; NSAIDs, non-steroidal anti-inflammatory drugs; PS, propensity score; Strat, stratification; TNFi, tumour necrosis factor alpha inhibitor; TV, time-varying.