Table.
Demographics, clinical features, and immunosuppressive therapy in patients with systemic sclerosis, stratified by anti-SARS-CoV-2 antibody response
| Patients with positive antibody response (n=70) | Patients with negative antibody response (n=30) | Total (n=100) | p value | ||
|---|---|---|---|---|---|
| 2013 American College of Rheumatology criteria | 68/70 (97%) | 26/30 (87%) | 94/100 (94%) | 0·064 | |
| Age, years* | 59·4 (49·1–66·1) | 60·5 (50·0–64·0) | 60·4 (49·6–64·9) | 0·88 | |
| Sex | |||||
| Female | 64/70 (91%) | 25/30 (83%) | 89/100 (89%) | 0·24 | |
| Male | 6/70 (9%) | 5/30 (17%) | 11/100 (11%) | 0.24 | |
| Race and ethnicity | |||||
| White | 55/70 (79%) | 18/30 (60%) | 73/100 (73%) | 0·080 | |
| Black | 9/70 (13%) | 3/30 (10%) | 12/100 (12%) | 1·00 | |
| South Asian | 3/70 (4%) | 2/30 (7%) | 5/100 (5%) | 0·64 | |
| East Asian | 1/70 (1%) | 4/30 (13%) | 5/100 (5%) | 0·030 | |
| Middle Eastern | 1/70 (1%) | 1/30 (3%) | 2/100 (2%) | 0·51 | |
| Hispanic or Latino | 4/63 (6%) | 3/28 (11%) | 7/91 (8%) | 0·67 | |
| Other | 1/70 (1%) | 2/30 (7%) | 3/100 (3%) | 0·21 | |
| Ever smoker | 21/59 (36%) | 10/27 (37%) | 31/86 (36%) | 0·90 | |
| BMI >30 kg/m2 | 19/70 (27%) | 4/27 (15%) | 23/100 (23%) | 0·13 | |
| Age of systemic sclerosis onset, years† | 39·4 (28·9–52·5) | 47·0 (28·9–53·2) | 42·2 (28·9–52·9) | 0·54 | |
| Disease duration, years* | 15·5 (8·2–20·8) | 9·8 (4·9–19·8) | 14·0 (7·6–20·3) | 0·14 | |
| Diffuse cutaneous subtype | 33/70 (47%) | 18/30 (60%) | 51/100 (51%) | 0·24 | |
| Maximum modified Rodnan skin score | 7 (4–20) | 14 (4–25) | 10 (4–21) | 0·43 | |
| Lowest FVC <70% | 29/52 (56%) | 13/24 (54%) | 42/76 (55%) | 0·90 | |
| Maximum right ventricular systolic pressure >40 mm Hg | 16/42 (38%) | 6/18 (33%) | 22/60 (37%) | 0·73 | |
| Renal crisis | 0/70 (0%) | 1/30 (3%) | 1/100 (1%) | 0·30 | |
| Maximum Medsger Raynaud's severity score ≥2‡ | 32/57 (56%) | 16/26 (62%) | 48/83 (58%) | 0·64 | |
| Maximum Medsger lung severity score ≥2‡ | 40/55 (73%) | 18/26 (69%) | 58/81 (72%) | 0·75 | |
| Maximum Medsger heart score ≥2‡ | 13/58 (22%) | 5/24 (21%) | 18/82 (22%) | 0·88 | |
| Maximum Medsger gastrointestinal score >2‡ | 38/58 (66%) | 13/26 (50%) | 51/84 (61%) | 0·18 | |
| Maximum Medsger kidney score ≥2‡ | 1/57 (2%) | 2/25 (8%) | 3/82 (4%) | 0·22 | |
| Maximum Medsger muscle score ≥2‡ | 6/58 (10%) | 4/26 (15%) | 10/84 (12%) | 0·49 | |
| Anti-centromere antibodies | 5/52 (10%) | 0/24 (0%) | 5/76 (7%) | 0·17 | |
| Anti-topoisomerase I antibodies | 18/51 (35%) | 10/25 (40%) | 28/76 (37%) | 0·69 | |
| RNA polymerase III antibodies§ | 10/41 (24%) | 9/17 (53%) | 19/58 (33%) | 0·035 | |
| Vaccine type | |||||
| BNT162b2 | 40/70 (57%) | 14/29 (48%) | 54/99 (55%) | 0·42 | |
| mRNA-1273 | 28/70 (40%) | 13/29 (45%) | 41/99 (41%) | 0·66 | |
| Ad26.COV2.S | 2/70 (3%) | 2/29 (7%) | 4/99 (4%) | 0·58 | |
| Time from vaccination to testing, days | 77 (36–124) | 86·5 (57–126) | 83·5 (48–124·5) | 0·24 | |
| Immunosuppressant therapy¶ | 56/70 (80%) | 30/30 (100%) | 86/100 (86%) | 0·0090 | |
| Mycophenolate therapy‖ | 41/70 (59%) | 24/30 (80%) | 65/100 (65%) | 0·04 | |
| Daily mycophenolate dose, mg‖ | 2000 (1000–2000) | 2500 (2000–3000) | 2000 (1500–3000) | 0·0080 | |
| Mycophenolate dose, g/day‖ | .. | .. | .. | 0·010 | |
| <2·0 | 15/41 (37%) | 3/24 (13%) | 18/65 (28%) | .. | |
| 2·0 to <3·0 | 17/41 (41%) | 10/24 (42%) | 27/65 (42%) | .. | |
| 3·0 | 9/41 (22%) | 11/24 (46%) | 20/65 (31%) | .. | |
| Methotrexate therapy | 13/70 (19%) | 4/30 (13%) | 17/100 (17%) | 0·52 | |
| Weekly methotrexate dose, mg | 20 (15–20) | 17·5 (12·5–22·5) | 20 (15–20) | 1·00 | |
| Rituximab therapy (within 15 months of vaccine)** | 4/70 (6%) | 9/30 (30%) | 13/100 (13%) | 0·0010 | |
| Hydroxychloroquine | 16/70 (23%) | 2/30 (7%) | 18/100 (18%) | 0·053 | |
| Prednisone | 18/70 (26%) | 5/30 (17%) | 23/100 (23%) | 0·33 | |
| Prednisone dose, mg | 8 (6–8) | 6 (5–8) | 8 (5–8) | 0·58 | |
| >1 immunosuppressant medication¶ | 9/70 (13%) | 5/30 (17%) | 14/100 (14%) | 0·62 | |
| Withheld immunosuppression | 9/56 (16%) | 2/23 (9%) | 11/79 (14%) | 0·49 | |
| Withheld mycophenolate | 4/40 (10%) | 0/23 (0%) | 4/63 (6%) | 0·29 | |
| Withheld methotrexate | 4/14 (29%) | 2/3 (67%) | 6/17 (35%) | 0·52 | |
Data are n (%) or median (IQR). FVC=forced vital capacity.
Age and disease duration were calculated at vaccination.
Onset of systemic sclerosis defined by the date of the first non-Raynaud's disease symptom.
Moderate-to-severe Raynaud's disease score: digital pits, ulceration, or gangrene. Moderate-to-severe lung score: FVC, diffusing capacity for carbon monoxide, or both <70% predicted, and mild-to-severe pH or oxygen dependence. Moderate-to-severe heart score: left ventricular ejection fraction <45%, clinical signs of left or right heart failure, or sustained clinically important arrhythmia. Moderate-to-severe gastrointestinal score: high-dose acid reflux medications, antibiotics for bacterial overgrowth, malabsorption syndrome, episodes of pseudo-obstruction or total parental nutrition requirement. Moderate-to-severe kidney score: serum creatinine ≥1·7 mg/dL or at least two urine proteins. Moderate-to-severe muscle score: strength of ≤3/5 in the upper or lower extremities or the requirement of ambulatory aids.
All patients with RNA polymerase III antibodies were on mycophenolate mofetil, except for one who was on rituximab. Among patients with RNA polymerase III antibodies who had a negative humoral response, median mycophenolate mofetil dose was 2750 mg per day. Among patients with RNA polymerase III antibodies who had a positive humoral response, median mycophenolate mofetil dose was 1250 mg per day.
Defined as more than one disease-modifying anti-rheumatic drug, biological therapy, or glucocorticoid dose (>5 mg prednisone or equivalent).
Includes mycophenolic acid and mycophenolate mofetil; mycophenolate 500 mg is equivalent to 360 mg mycophenolic acid.
All patients who had ever received rituximab infusion therapy received it within 15 months of vaccine.