Baseline demographic, clinical, MRI and treatment response characteristics of the cluster-analyses based ECM endotypes
| All (n=135) | Endotype1 (n=41) | Endotype2 (n=53) | Endotype3 (n=41) | P value | |
| Demographic feature | |||||
| Age, years | 36.3 (10.1) | 34.6 (8.7) | 38.4 (11.7) | 35.2 (9.0) | 0.338 |
| Male sex, no. (%) | 78 (57.8%) | 20 (48.8%) | 34 (64.2%) | 24 (58.5%) | 0.324 |
| HLA-B27, positive, no. (%) | 110 (81.5%) | 33 (80.5%) | 42 (79.2%) | 35 (85.4%) | 0.736 |
| Symptom duration, years | 10.7 (8.8) | 10.3 (7.4) | 10.4 (9.9) | 11.4 (9.0) | 0.693 |
| CRP, mg/L | 13.3 (18.3) | 26.4 (17.4) | 5.6 (15.2) | 10.3 (16.0) | < 0.001*† |
| CRP≥3 mg/L | 85 (63.0%) | 40 (97.6%) | 19 (35.8%) | 26 (63.4%) | < 0.001*†‡ |
| Clinical examination | |||||
| BASDAI (0–10) | 5.5 (2.0) | 6.0 (2.0) | 5.6 (2.1) | 5.0 (1.8) | 0.074*‡ |
| ASDAS | 3.4 (0.8) | 4.2 (0.6) | 3.0 (0.6) | 3.1 (0.5) | < 0.001*‡ |
| BASFI (0–10) | 4.2 (2.3) | 5.0 (2.2) | 4.0 (2.2) | 3.5 (2.1) | 0.017‡ |
| BASMI (0–10) | 2.3 (2.1) | 2.6 (2.3) | 2.2 (2.0) | 2.0 (1.9) | 0.481 |
| Tender joint count 0–28, no. (%) ≥1 | 29 (21.5%) | 9 (22.0%) | 11 (20.8%) | 9 (22.0%) | 0.986 |
| Swollen joint count 0–28, no. (%) ≥1 | 11 (8.1%) | 6 (14.6%) | 4 (7.5%) | 1 (2.4%) | 0.128 |
| MRI inflammation and structural damage | |||||
| SPARCC SIJ inflammation score (0–48) | 8.7 (10.0) | 10.2 (11.5) | 7.9 (8.5) | 8.3 (10.1) | 0.759 |
| SPARCC SSS fat lesion score (0–40) | 11.5 (12.6) | 12.6 (14.9) | 11.4 (12.2) | 10.4 (10.5) | 0.986 |
| SPARCC SSS erosion score (0–20) | 3.5 (4.2) | 3.1 (4.3) | 3.4 (4.0) | 4.0 (4.4) | 0.435 |
| SPARCC SSS backfill score (0–20) | 3.8 (5.1) | 4.3 (5.7) | 4.0 (5.1) | 3.1 (4.5) | 0.747 |
| SPARCC SSS ankylosis score (0–20) | 4.6 (7.0) | 6.5 (8.0) | 2.8 (5.5) | 5.2 (7.3) | 0.03 * |
| SPARCC SIJ inflammation score≥2, no (%) | 89 (66.4%) | 29 (70.7%) | 35 (67.3%) | 25 (61.0%) | 0.636 |
| SPARCC SSS fat lesion score≥2, no (%) | 98 (73.1%) | 28 (68.3%) | 40 (76.9%) | 30 (73.2%) | 0.648 |
| SPARCC SSS erosion score≥2, no (%) | 72 (53.7%) | 20 (48.8%) | 28 (53.8%) | 24 (58.5%) | 0.675 |
| SPARCC SSS backfill score≥2, no (%) | 65 (48.5%) | 20 (48.8%) | 27 (51.9%) | 18 (43.9%) | 0.744 |
| SPARCC SSS ankylosis score≥2, no (%) | 51 (38.1%) | 20 (48.8%) | 14 (26.9%) | 17 (41.5%) | 0.085 |
| Treatment response§ | n=94 | n=27 | n=39 | n=28 | |
| BASDAI50 responders, no (%) | 65 (70.7%) | 21 (77.8%) | 21 (56.8%) | 23 (82.1%) | 0.053† |
| ASDAS no improvement | 19 (22.4%) | 2 (8.0%) | 11 (33.3%) | 6 (22.2%) | 0.072* |
| ASDAS clinical important improvement | 28 (32.9%) | 5 (20.0%) | 13 (39.4%) | 10 (37.0%) | 0.256 |
| ASDAS major improvement | 38 (44.7%) | 18 (72.0%) | 9 (27.3%) | 11 (40.7%) | 0.003* |
| Biomarker levels | |||||
| C1M (ng/mL) | 92.3 (89.3) | 159.3 (84.) | 49.6 (56.9) | 80.3 (90.2) | |
| CPa9-HNE (ng/mL) | 100.2 (53.6) | 143.8 (57.) | 78.7 (34.6) | 84.5 (44.1) | |
| VICM (ng/mL) | 5.3 (4.4) | 8.2 (5.8) | 3.9 (3.0) | 4.0 (2.5) | |
| CRPM (ng/mL) | 12.6 (9.2) | 16.1 (15.3) | 10.3 (3.0) | 12.2 (4.1) | |
| PRO-C2 (ng/mL) | 20.9 (10.4) | 18.8 (6.5) | 14.9 (5.2) | 30.9 (11.5) |
Except where indicated otherwise, mean±SD is presented. Mann-Whitney and χ2 test was used to compare differences between the clusters. Inter-group comparisons were conducted among endotypes, and statistical significance is indicated as follows:
*p<0.05 for comparisons between Endotype1 and Endotype2.
†p<0.05 for Endotype2 versus Endotype3.
‡p<0.05 for Endotype1 versus Endotype3.
§Analyses of treatment response were based on patients from ASIM and DANISH only.
ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; BASMI, Bath Ankylosing Spondylitis Metrology Index; CRP, C reactive protein; HLA, human leucocyte antigen; SIJ, sacroiliac joint; SPARCC, Spondyloarthritis Research Consortium of Canada; SSS, SI joint structural lesion score.