Supplemental Figure 1: Study Time Periods Supplemental Material

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Supplemental Figure 1: Study Time Periods

SLE Index Oral Belimumab Index Date Coricosteroid Date Date of first Index Date Date of first SLE Diagnosis Date of first Oral belimumab claim Corticosteroid Fill 1/1/2011 5/31/2019

12 Month Pre-Index Variable Length Post-Index Period Period From the SLE index date to disenrollment or study end. Minimum of 12 months

12 Month Post-Corticosteroid Period

6-Month 6- Month Pre-Belimumab Period Post-Belimumab Period

Birt JA, et al. Lupus Sci Med 2020; 7:e000435. doi: 10.1136/lupus-2020-000435 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Lupus Sci Med

Supplementary Table 1: List of drugs used in assessing treatment landscape of SLE

Category Drugs Antimalarials chloroquine and hydroxychloroquine Biologics belimumab (intravenous or subcutaneous), and rituximab Corticosteroids alclometasone, amcinonide, betamethasone, clobetasol , clocortolone, cortisone, deflazacort, desonide, desoximetasone, dexamethasone, diflorasone, fludrocortisone, fluocinolone, fluocinonide, flurandrenolide, fluticasone, halcinonide, halobetasol, hydrocortisone, methylprednisolone, mometasone, prednicarbate, prednisolone, prednisone, triamcinolone Immunosuppressants azathioprine, cyclophosphamide, cyclosporine, intravenous immunoglobulin, leflunomide, methotrexate, mycophenolate, and tacrolimus Nonsteroidal anti- bromfenac, celecoxib, diclofenac, etodolac, fenoprofen, flurbiprofen, inflammatories ibuprofen, indomethacin, ketoprofen, meclofenamate, mefenamic acid, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, rofecoxib, sulindac, tolmetin, and valdecoxib Opioids, strong buprenorphine,fentanyl,hydromorphone (or oxymorphone), methadone, morphine, oxycodone, tapentadol, butorphanol, dezocine, hydrocodone, levomethadyl, levorphanol, meperidine,nalbuphine, pentazocine Opioids, weak codeine, dihydrocodeine, tramadol, propoxyphene (included but no longer used in US)

Supplementary Table 2: Prescribing patterns in the 6 months before and after initiation of belimumab treatment segmented by belimumab route of administration 6 Months Before 6 Months After p-value, 6 Months Before 6 Months After p-value, Belimumab IV Belimumab IV pre vs. Belimumab SC Belimumab SC pre vs. post Initiation Initiation post Initiation Initiation N = 1,570 N = 1,570 N = 140 N = 140 Patients with SLE Drugs (N, %) 1,518 96.7% 1,570 100.0% 0.349 137 97.9% 140 100.0% 0.857 Class 1: Antimalarials 1,079 68.7% 996 63.4% 0.068 95 67.9% 92 65.7% 0.826 Class 2: Prescription NSAIDs 563 35.9% 541 34.5% 0.508 42 30.0% 41 29.3% 0.913 Class 3: Corticosteroids 1,313 83.6% 1,256 80.0% 0.261 116 82.9% 101 72.1% 0.309 Oral 1,145 72.9% 1,001 63.8% 0.002 103 73.6% 91 65.0% 0.389 Infusion/Injection 532 33.9% 662 42.2% 0.000 48 34.3% 30 21.4% 0.042 Topical 237 15.1% 224 14.3% 0.545 15 10.7% 13 9.3% 0.705 Class 4: Immunosuppressants 927 59.0% 803 51.1% 0.003 78 55.7% 66 47.1% 0.317 Class 5: Biologics 1,570 100.0% 140 100.0% Belimumab 1,570 100.0% 140 100.0% Belimumab IV 1,570 100.0% 5 3.6% Belimumab SC 8 0.5% 140 100.0% Rituximab IV 13 0.8% 1 0.7%

Number of claims per patient, among all patients (Mean, SD) Class 1: Antimalarials 2.15 2.05 2.00 2.06 <0.001 2.14 2.08 2.05 2.17 0.370 Class 2: Prescription NSAIDs 0.91 1.60 0.85 1.60 0.101 0.74 1.51 0.63 1.33 0.252 Class 3: Corticosteroids 3.18 2.83 3.77 3.45 <0.001 2.94 2.54 2.45 2.38 0.012 Oral 2.28 2.19 2.01 2.22 <0.001 2.15 2.01 1.93 2.07 0.168 Infusion/Injection 0.64 1.39 1.54 2.57 <0.001 0.66 1.38 0.40 0.90 0.009 Topical 0.26 0.83 0.22 0.67 0.047 0.14 0.42 0.12 0.42 0.733 Class 4: Immunosuppressants 2.08 2.48 1.73 2.35 <0.001 2.26 2.63 1.66 2.38 0.001 Class 5: Biologics 6.06 2.08 5.27 1.90 Belimumab 6.04 2.10 5.26 1.92 Belimumab IV 6.03 2.10 0.12 0.65

Belimumab SC 0.01 0.20 5.14 1.99 Rituximab IV 0.02 0.24 0.01 0.17 Number of Classes Utilized, other than biologics (N, %) No therapy 52 3.3% 71 4.5% 0.087 3 2.1% 7 5.0% 0.206 One drug class (monotherapy) 195 12.4% 264 16.8% 0.001 25 17.9% 33 23.6% 0.294 Two drug classes 508 32.4% 545 34.7% 0.254 46 32.9% 43 30.7% 0.750 Three drug classes 589 37.5% 518 33.0% 0.033 50 35.7% 47 33.6% 0.761 Four drug classes 226 14.4% 172 11.0% 0.007 16 11.4% 10 7.1% 0.239 Opioid Use (N, %) 843 53.7% 801 51.0% 0.300 58 41.4% 60 42.9% 0.854 Weak opioids 332 21.1% 294 18.7% 0.129 24 17.1% 18 12.9% 0.355 Strong opioids 658 41.9% 642 40.9% 0.657 41 29.3% 53 37.9% 0.216 Acute Opioid Use 505 59.9% 452 56.4% 0.153 33 56.9% 34 56.7% 0.980 Chronic opioid use 338 40.1% 349 43.6% 0.153 25 43.1% 26 43.3% 0.980 Oral Corticosteroid Dosing1 Average daily dose (Mean, SD)2,3 14.6 18.6 11.8 18.1 <0.001 13.4 16.1 12.6 17.3 0.512 Low (N, %) 197 12.5% 237 15.1% 0.055 13 9.3% 18 12.9% 0.369 Medium (N, %) 352 22.4% 307 19.6% 0.080 37 26.4% 27 19.3% 0.211 High (N, %) 591 37.6% 453 28.9% <0.001 52 37.1% 44 31.4% 0.414

1 Oral steroid dosing can only be reliability calculated among outpatient pharmacy claims, therefore oral steroids identified on outpatient office visit claims were not included in this analysis. This occurred for <0.6% of belimumab patients in both time periods reported. 2 Daily dose in prednisone equivalents = (strength * quantity)/ days of supply. Claims with <=0 value for fields used to calculate dose were dropped (resulted in dropping <1% of patients without a valid claim). 3For those with an invalid daily dose (>100 mg/day), doses were capped at 100 mg. This occurred for <2% of belimumab patients in both time periods reported.

Birt JA, et al. Lupus Sci Med 2020; 7:e000435. doi: 10.1136/lupus-2020-000435