| 1. |
|
|
| 2. |
- Sieberts, SK, et al.
(författare)
-
Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis
- 2016
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 12460-
-
Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h2=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Hambardzumyan, K., et al.
(författare)
-
Association of female sex and positive rheumatoid factor with low serum infliximab and anti-drug antibodies, related to treatment failure in early rheumatoid arthritis : results from the SWEFOT trial population
- 2019
-
Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 48:5, s. 362-366
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Infliximab-treated patients with rheumatoid arthritis (RA) may respond insufficiently due to low serum infliximab (sIFX) levels, caused by anti-drug antibodies (ADAs). However, monitoring of sIFX and ADAs is not routinely implemented, and levels for optimal outcome have not been validated. We searched for predictors for sIFX < 0.2 μg/mL and ADA development in a randomized setting. Methods: In the SWEFOT trial, of 128 patients randomized to methotrexate + IFX therapy, 101 had serum samples at 3, 9, and 21 months that were analysed for sIFX [enzyme-linked immunosorbent assay (ELISA)] and ADAs [ELISA, and precipitation and acid dissociation (PandA) when sIFX > 0.2 μg/mL]. The primary and secondary outcome measures were low disease activity [LDA = 28-joint Disease Activity Score (DAS28) ≤ 3.2] and remission (DAS28 < 2.6). Baseline characteristics were assessed as potential predictors of sIFX < 0.2 μg/mL or ADA positivity, using logistic regression. Results: Categorization of sIFX levels into < 0.2, 0.2–2.9, 3.0–7.0, and > 7.0 μg/mL showed a dose–response association with LDA (30%, 64%, 67%, and 79%, respectively, p = 0.008) and remission (10%, 45%, 39%, and 66%, p = 0.004) at trial cessation (21 months). Female patients had sIFX < 0.2 μg/mL more often than males (35% vs 7%, p = 0.006), with a similar trend for rheumatoid factor (RF)-positive vs RF-negative patients (34% vs 16%, p = 0.059). ADA positivity showed similar patterns, also after adjustment for potential confounders (female sex: p = 0.050; RF positivity: p = 0.067). PandA captured four highly ADA-reactive patients with sIFX > 0.2 μg/mL, of whom three were ADA positive at other time-points, all with high DAS28 at follow-up. Conclusion: In early RA patients receiving IFX as a second-line agent, sIFX < 0.2 μg/mL and ADA development were associated with treatment failure and were more common in females, with a similar trend for RF positivity. Our findings support the use of therapeutic drug monitoring, and PandA in ADA-negative non-responders. Trial registration: SWEFOT NCT00764725 (https://clinicaltrials.gov/ct2/show/NCT00764725).
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
