Session Information
Date: Monday, October 22, 2018
Title: Systemic Lupus Erythematosus – Clinical Poster II: Biomarkers and Outcomes
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: management of systemic lupus erythematosus (SLE) patients is challenging because of the heterogeneity of the disease. While treatment of renal nephritis is more standardized, treatment of non-renal refractory lupus remains controversial. Our objective was to identify non-renal non-neurologic refractory SLE patients in our cohort and described therapeutic behaviors in these patients.
Methods: all SLE patients (ACR and/or SLICC criteria) seen at a university based hospital between 2000 and 2017 were included and electronic medical records manually reviewed. Patients’ characteristics, clinical manifestations and treatment patterns were recorded. Refractory lupus was defined as a patient with a SLEDAI score >= 6 (excluding renal and CNS manifestations) despite being on a stable treatment regimen for ≥ 30 days. Stable treatment could include prednisone alone (7.5 to 40 mg/d) or combined (0 to 40 mg/d) with antimalarial drugs and immunosuppressant therapies.
Results:
a total of 257 lupus patients were included, 230 females (89.5%, 95% CI 85.1-92.7), mean age at diagnosis 29.9 years (SD 16.4). 211 patients (82.1%) fulfilled ACR criteria and 255 (99.2%) SLICC criteria. Type of clinical manifestations and treatments received during first year of disease, and cumulative are shown in table 1. After a median follow-up of 5.7 years (IQR 2.4-10.2), 16 patients (6.2%, 95% CI 3.8-9.9) met the refractory lupus criteria, with a median disease duration of 9.6 years (IQR 3.9-19.1). At that time, 87.5% of patients (95% CI 56.9-97.4) had low complement and 81.3 % (95% CI 51.4-94.7) had positive antiDNA antibodies. Main reasons for being refractory were mucocutaneous disease (50%, 95% CI 24.9-75.0) and arthritis (37.5%, 95% CI 16.1-65.2). Treatments received after being refractory were: corticosteroids > 20 mg/d of prednisone in 8 patients, mycophenolate in 1, rituximab in 5 and belimumab in 7, with optimal response in all of them (table 2). In a multivariate logistic regression analysis, only a younger age was associated with refractory disease (OR 0.93, 95% CI 0.87-0.99, p=0.03).
Conclusion: despite receiving intensive treatments during follow-up (prednisone >20 mg/d in 73.5% of patients, antimalarial in 94.9% and immunosuppressant in 67.5%), 6.2% of patients met refractory criteria.
Table 1. SLE patients’ clinical manifestations and treatments at first year and cumulative
|
At first year of SLE (n=257) |
Cumulative (n=257) |
|
| Acute cutaneous lupus (SLICC definition), n (%, 95% CI) | 140 (54.7, 48.5-60.7) | 160 (62.3, 56.1-68.1) |
| Chronic cutaneous lupus, n (%,95% CI) | 11 (4.3, 2.4-7.6) | 15 (5.8, 3.5-9.5) |
| Oral/nasal ulcers, n (%,95% CI) | 57 (22.3, 17.5-27.8) | 68 (26.5, 21.4-32.2) |
| Alopecia, n (%,95%CI) | 93 (36.3, 30.6-42.4) | 122 (47.5, 41.4-53.6) |
| Arthralgia, n (%,95% CI) | 188 (73.4, 67.6-78.5) | 205 (79.8, 74.4-84.3) |
| Arthritis, n (%,95% CI) | 133 (51.9, 45.8-58.1) | 140 (54.5, 48.3-60.5) |
| Myositis, n (%,95% CI) | 2 (0.8, 0.2-3.1) | 3 (1.2, 0.4-3.6) |
| Pleural effusion, n (%,95% CI) | 27 (10.6, 7.3-14.9) | 33 (12.8, 9.2 -17.5) |
| Pericardial effusion, n (%,95% CI) | 34 (13.3, 9.6-18.1) | 45 (17.5, 13.3-22.7) |
| Hemolytic anemia, n (%,95% CI) | 11 (4.3, 2.4-7.6) | 13 (5.1, 2.9-8.5) |
| Leukopenia < 3000, n (95%%, CI) | 55 (21.5, 16.8-26.9) | 73 (28.4, 23.2-34.3) |
| Thrombocytopenia < 100000, n (%,95%CI) | 30 (11.7, 8.3-16.3) | 43 (16.7, 12.6-21.8) |
| Renal involvement, n (%,95%CI) | 110 (42.8, 36.8-48.9) | 148 (57.6, 51.4-63.5) |
| Neurologic involvement, n (%, 95% CI) | 15 (5.9, 3.5-9.5) | 24 (9.3, 6.3-13.6) |
| SLEDAI >= 6, n (%, 95% CI) | 171 (66.5, 60.5-72.1) | 196 (76.3, 70.6-81.1) |
| Corticosteroids low dose, < prednisone 7.5 mg/d, n (%,95% CI) |
234 (91.1, 86.9-93.9) |
241 (93.8, 90.1-96.2) |
| Corticosteroids dose > 20 mg/d prednisone, n (%, 95%CI) |
152 (59.1, 52.9-65.1) |
189 (73.5, 67.8-78.6) |
| Antimalarial, n (%, 95% CI) |
210 (82.1, 76.8-86.3) |
244 (94.9, 91.4 – 97.1) |
| Methotrexate, n (%, 95% CI) | 18 (7.1, 4.5-10.9) | 37 (14.4, 10.6 – 19.3) |
| Azathioprine, n (%, 95%CI) | 36 (14.1, 10.3-18.9) | 88 (34.2, 28.7-40.3) |
| Mycophenolate, n (%, 95%CI) | 45 (17.6, 13.4-22.8) | 111 (43.2, 37.2-49.3) |
| Cyclophosphamide, n (%, 95% CI) | 57 (22.2, 17.5-27.7) | 98 (38.1, 32.3-44.3) |
| Cyclosporine, n (%, 95% CI) | 2 (0.8, 0.2-3.1) | 7 (2.7, 1.3-5.6) |
| Rituximab, n (%, 95% CI) | 3 (1.2, 0.4-3.6) | 30 (11.7, 8.3- 16.2) |
| Belimumab, n (%, 95% CI) | 0 | 7 (2.7, 1.3-5.6) |
| Other biologics, n (%, 95% CI) | 0 | 1 (0.4, 0.1-2.7) |
| Any immunosuppressant, n (%, 95% CI) | 127 (45.8, 40.0-51.8) | 187 (67.5, 61.7-72.8) |
Table 2. Refractory SLE Patients’ characteristics
|
Refractory patients (n=16) |
|
|
Female, n (%,95% CI) |
15 (93.7, 64.7-99.2) |
|
Median age at SLE diagnosis, years (IQR) |
20.9 (19.5-25.7) |
|
Median age at refractory disease, years (IQR) |
35.7 (27.6-39.0) |
|
Median disease duration at refractory time, years (IQR) |
9.6 (3.9-19.1) |
|
Median SLEDAI score at refractory time (RIC) |
9.5 (8-11) |
|
Clinical involvement at refractory time: |
|
|
Vasculitis , n (%, 95% CI) |
2 (12.5, 2.6-43.0) |
|
Mucocutaneous disease, n (%, 95% CI) |
8 (50, 24.9-75.0) |
|
Fever, (%, 95% CI) |
2 (12.5, 2.6-43.0) |
|
Low Complement levels, (%, 95% CI) |
14 (87.5, 56.9-97.4) |
|
DNA antibodies, (%, 95% CI) |
13 (81.3, 51.4-94.7) |
|
Arthritis, n (%, 95% CI) |
6 (37.5, 16.1-65.2) |
|
Miositis, n (%, 95% CI) |
0 |
|
Pleural effusion, n (%, 95% CI) |
1 (6.3, 0.7-39.3) |
|
Pericardial effusion, n (%, 95% CI) |
0 |
|
Hemolytic anemia, n (%, 95% CI) |
0 |
|
Leukopenia < 3000, n (%, 95% CI) |
3 (18.7, 5.3-48.6) |
|
Thrombocytopenia < 100000, n (%, 95% CI) |
2 (12.5, 2.6-43.0) |
|
Renal involvement, n (%, 95% CI) |
3 (18.7, 5.3-48.6) |
|
Neurologic involvement, n (%, 95% CI) |
0 |
|
Treatments received after being refractory: |
|
|
Corticosteroids, any dose, n (%, 95%CI) |
11 (68.7, 40.1-87.8) |
|
Prednisone dose (or equivalent) > 20 mg/d, n (%, 95% CI) |
8 (50, 24.9-75.0) |
|
Mycophenolate, n (%, 95% CI) |
1 (6.3, 0.7-39.3) |
|
Rituximab, n (%, 95% CI) |
5 (31.2, 12.2-59.8) |
|
Belimumab, n (%, 95% CI) |
7 (43.7, 20.4- 70.2) |
To cite this abstract in AMA style:
Scaglioni V, Scolnik M, Soriano ER, Pons-Estel GJ. Refractory Lupus Patients: How Frequent Do We See Them in the 21st Century? [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/refractory-lupus-patients-how-frequent-do-we-see-them-in-the-21st-century/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/refractory-lupus-patients-how-frequent-do-we-see-them-in-the-21st-century/