Autoimmune disease phenotype, antibodies and treatment for included patients
| Date of first ICI exposure | Autoimmune disease phenotype | Date of IRAE | Treatment of IRAE | IRAE response to treatment | Imaging, synovial fluid and other findings | Autoantibody results | |
|---|---|---|---|---|---|---|---|
| 1 | 21/2/2014 | Colitis Inflammatory arthritis | 21/3/2014 2/2015: reported 16/6/2015: seen | Prednisone 120 mg daily, tapered off over 3 months. ICI held for 3 months Prednisone 10 mg daily with suboptimal response. ICI stopped and prednisone increased to 40 mg daily. Continued disease activity, so MTX 15 mg weekly and adalimumab weekly added to regimen with improvement | Resolution of colitis. Able to go back on ICI Improvement with adalimumab and MTX. Able to come off prednisone | MRI: tibiotalar and subtalar joint effusions with marked synovitis | ANA, RF, CCP, Ro, La, dsDNA, RNP, Sm, myositis panel*, Scl70, HLA-B27 negative |
| 2 | 7/2013 | Colitis (on anti-CTLA-4) Thyroiditis/hypothyroid Inflammatory arthritis (on anti-PD-1) | 10/2013 10/2013 8/2014 | Prednisone 1 mg/kg/day Prednisone 40 mg, tapered to 7 mg/day MTX Infliximab Etanercept | Resolution of colitis Poor response to steroids (4 months) Poor response to MTX (5 months) Initial response to infliximab, d/c due to AE (nausea, chills) Marked response to etanercept | Synovial fluid: WBC 12 700 (75% PMN) Ultrasound: Doppler-positive synovitis in the right ankle | RF, CCP negative |
| 3 | 14/11/2014 | Inflammatory arthritis | 3/8/2015—reported 17/9/2015—seen | Intra-articular triamcinolone Prednisone 40 mg daily, tapered off over 1 month. ICI stopped, resumed 40 mg prednisone | Temporary relief from intra-articular triamcinolone, partial relief from 40 mg prednisone but not smaller doses | Ultrasound: Doppler-positive synovitis and erosions at elbow Subsequently developed metastatic lesion at distal humerus | ANA, RF, CCP, Ro, La, RNP, Sm, dsDNA, P-ANCA, C-ANCA, HLA-B27, Scl70, RNA pol III, cardiolipin, β-2-glycoprotein antibodies negative |
| 4 | 21/10/2015 | Colitis Inflammatory arthritis | 11/2015 1/2016– | Prednisone starting at 160 mg daily tapered off over 1 month Prednisone 120 mg daily tapered down to 40 mg daily Intra-articular triamcinolone Adalimumab initiated | Resolved Initial steroid treatment with no improvement, after 2 weeks high-dose steroids some improvement in pain and swelling. Marked improvement with adalimumab allowing steroid taper | Synovial fluid: 11 950 WBCs (92% PMN) | ANA, RF, CCP, Ro, La, RNP, Sm, dsDNA, P-ANCA, C-ANCA, HLA-B27, Scl70, cardiolipin antibodies, β-2-glycoprotein antibodies negative |
| 5 | 26/3/2015 | Inflammatory arthritis | 21/5/2015—reported 25/6/2015—seen | Prednisone 10 mg daily, tapered to 7.5 mg daily after 3 months | Good response with improvement of symptoms | None available | ANA 1:80 (speckled) Anti-Ro positive RF, CCP, RNP, Sm, Scl70, myositis panel negative |
| 6 | 3/2012 | Colitis Hypothyroidism Reactive arthritis (inflammatory arthritis, conjunctivitis) | 5/2013 5/2/2014 (recurrence after re-dosing with ICI 1 month prior) 20/12/2013 5/1/2014—seen 7/3/2014 (flare after infliximab) | Prednisone 80 mg/day tapered to 20 mg/day Infliximab (one dose) Prednisone 80 mg/day tapered to 20 mg/day Infliximab (two doses) Adalimumab Hormone replacement Prednisone 40 mg/day tapered over 1 months to 10 mg/day Intra-articular triamcinolone Prednisone 1 mg/kg/day Intra-articular triamcinolone | Initial response high dose steroids, recurrence with steroid taper Resolved with infliximab Poor response to high dose steroids Adverse event (pneumonia) Resolved Initial response to prednisone 40 mg, with recurrence of joint pain and stiffness at 10 mg/day Improved with steroid injection Improved with steroids Improved with adalimumab | Colonoscopy: mild, left-sided colitis (descending colon, sigmoid colon and rectum notable for mild erythema without ulceration) Knee radiographs: large suprapatellar effusion, no erosions Synovial fluid analysis: WBC 28455 (70% PMNs) | ANA, RF, CCP, antihistone negative |
| 7 | 3/3/2015 | Inflammatory arthritis Thyroiditis/hypothyroidism | 19/11/2015—reported 7/12/15—seen 17/4/2015 | Prednisone 10 mg daily Intra-articular triamcinolone Colchicine 0.6 mg daily Propranolol initially, Levothyroxine for subsequent hypothyroidism | Improvement of symptoms on 10 mg prednisone, but progressive symptoms involving the shoulder, knee, wrist and elbow requiring 40 mg prednisone for relief | Ultrasound: Synovitis with positive Doppler signal in knee, elbow Synovial fluid: 9854 WBC (86% PMN, 14% mononuclear, monosodium urate crystals present) | ANA, RF, CCP, Ro, La, RNP, Sm, dsDNA, P-ANCA, C-ANCA, HLA-B27, Scl70, RNA pol III, cardiolipin antibodies, β-2-glycoprotein antibodies negative |
| 8 | 26/2/2015 | Inflammatory arthritis | 5/2015—reported 9/12/2015—seen | Dexamethasone 8 mg daily for brain metastasis, no additional corticosteroids added | Improvement of joint symptoms on dexamethasone | None | ANA, RF, CCP, Ro, La, RNP, Sm, dsDNA, P-ANCA, C-ANCA, HLA-B27, Scl70, RNA pol III, cardiolipin antibodies, β-2-glycoprotein antibodies negative |
| 9 | 16/7/2015 | Inflammatory arthritis | 12/2015—reported 2/2016—seen | Celecoxib twice daily, intra-articular triamcinolone | None available | ANA, RF, CCP, Ro, La, RNP, Sm, dsDNA, P-ANCA, C-ANCA, Scl70, cardiolipin antibodies, β-2-glycoprotein antibodies negative | |
| 10 | 1/5/2015 | Pneumonitis Acute sicca | 23/7/15 9/7/15—reported 30/7/15—seen | Prednisone 80 mg daily, tapered over 2 months Pilocarpine for symptoms | Improvement of imaging and symptoms Improvement of xerostomia | None available | ANA 1:320 (nucleolar) RF 38 (ULN 35) Anti-EJ antibodies positive, rest of myositis panel negative. Ro, La, RNP, Sm, Scl70 negative |
| 11 | 24/4/2015 | Acute sicca | 6/2015 | Prednisone 0.5 mg/kg/day, increased to 1 mg/kg/day, tapered to until discontinued Cevimeline for symptoms | No improvement No benefit | ANA 1:320 homogenous Ro, La, RF negative | |
| 12 | 6/9/2011 nivolumab 8/3/2013 ipilimumab | Acute sicca Interstitial nephritis Insulin-dependent diabetes Colitis | 1/5/2012 22/5/2012—seen 1/5/2012 3/2013 4/2013 | Prednisone 1 mg/kg/day Prednisone 1 mg/kg/day Insulin Dexamethasone 8 mg twice a day tapered then discontinued | Improvement in xerostomia Improvement in creatinine Maintained on insulin Resolved with steroids | Creatinine 3.1 BUN 36 Renal biopsy: acute and evolving chronic interstitial inflammation with some T cells and focally numerous eosinophils suggesting a hypersensitivity reaction. The T-cell-rich lymphocytic infiltrate in the interstitial kidneys suggested an autoimmune interstitial nephritis | ANA 1:80 speckled Ro, La, RF, P-ANCA, C-ANCA negative |
| 13 | 1/4/2015 | Acute sicca with parotid swelling | 12/2015 | Prednisone 40 mg daily Cevilemine for symptomatic relief of xerostomia | Improved parotid swelling, prednisone tapered off over 6 weeks | Ultrasound bilateral parotid glands: hypoechoic foci consistent with lymphocytic aggregates, >50% of gland involved | La/SSB antibodies positive. ANA, Ro, RNP, Sm, RF, CCP, myositis panel, anti-dsDNA, P-ANCA, C-ANCA negative |
*Myositis panel tests for antibodies to Jo-1, SRP, EJ, OJ, PL-7, PL-12, Mi-2, Ku.
AE, adverse events; ANA, antinuclear antibody; ANCA, antineutrophil cytoplasmic autoantibody; BUN, blood urea nitrogen; CCP, cyclic citrullinated peptide; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; HLA, human leucocyte antigen; ICI, immune checkpoint inhibitor; MTX, methotrexate; PMN, polymorphonuclear leucocytes; RF, rheumatoid factor; RNP, ribonuclear protein antibody; ULN, upper limit of normal; WBC, white blood cells.