Table 4.
Details concerning patients with ICI associated temporal arteritis (n: 18), polymyalgia rheumatica (n: 16) or vasculitis (n: 82) collected from VigiBase (last accessed: 01/2018).
| Temporal arteritis | Polymyalgia Rheumatica | Vasculitis | ||||
|---|---|---|---|---|---|---|
| Characteristics | n (%) | Data availability, n (%) | n (%) | Data availability, n (%) | n (%) | Data availability, n (%) |
| Reporting region | 18 (100.0) | 16 (100.0.0) | 82 (100.0) | |||
| Americas : | 9 (50.0) | 4 (25.0) | 33 (40.2) | |||
| Europe | 8 (44.4) | 6 (37.5) | 40 (48.8) | |||
| Asia | 1 (5.6) | 6 (37.5) | 9 (11.0) | |||
| Reporters | 18 (100.0) | 16 (100.0) | 81 (98.8) | |||
| Healthcare professional | 17 (94.4) | 15 (93.8) | 73 (90.1) | |||
| Non-healthcare professional | 1 (5.6) | 1 (6.2) | 8(9.9) | |||
| Reporting year | 18 (100.0) | 16 (100.0) | 82 (100.0) | |||
| 2018 (thru February the 16th 2018) | 2 (11.1) | 0 (0.0) | 2 (2.4) | |||
| 2017 | 5 (27.8) | 12 (75.0) | 44 (53.7) | |||
| 2016 | 4 (22.2) | 3 (18.8) | 17 (20.7) | |||
| 2015 | 4 (22.2) | 0 (0.0) | 10 (12.2) | |||
| 2012–2014 | 3 (16.7) | 1 (6.2) | 9 (11.0) | |||
| Gender | 17 (94.5) | 15 (93.8) | 77 (93.9) | |||
| Male | 9 (52.9) | 10 (66.7) | 45 (58.4) | |||
| Female | 8 (47.1) | 5 (33.3) | 32 (41.6) | |||
| Age at onset, mean ± SD, years | 72.93 ± 8.1 | 14 (77.8) | 75.54 ± 6.4 | 13 (81.3) | 68.24 ± 11.8 | 67 (81.7) |
| [min-max] | [60–83] | [63–88] | [31–88] | |||
| Suspected Drugs* | 18 (100.0) | 16 (100.0) | 82 (100.0) | |||
| Only ICI | 14 (77.8) | 16 (100) | 71 (86.6) | |||
| ICI + 1 other drug | 2 (11.1) | 0 (0.0) | 7(8.5) | |||
| ICI + ≥2 other drugs | 2 (11.1) | 0 (0.0) | 4(4.9) | |||
| Drugs | 18 (100.0) | 16 (100.0) | 82 (100.0) | |||
| Monotherapy with Anti PD1/PD-L1 | 7 (38.9) | 14 (87.6) | 56 (68.3) | |||
| - Nivolumab | 3 (16.7) | 11 (68.8) | 33 (40.3) | |||
| - Pembrolizumab | 4 (22.2) | 3 (18.8) | 20 (24.4) | |||
| - Durvalumab | 0 (0.0) | 0 (0.0) | 1 (1.2) | |||
| - Atezolizumab | 0 (0.0) | 0 (0.0) | 2 (2.4) | |||
| Monotherapy with Anti CTLA-4 | 10 (55.5) | 1 (6.2) | 18 (22.0) | |||
| - Ipilimumab | ||||||
| Combination therapy | 1 (5.6) | 1 (6.2) | 8(9.7) | |||
| - Nivolumab + Ipilimumab | 1 (5.6) | 1 (6.2) | 7(8.5) | |||
| - Pembrolizumab + Ipilimumab | 0 (0.0) | 0 (0.0) | 1 (1.2) | |||
| Drug dosing | ||||||
| Ipilimumab | 7 (63.6) | 1 (50.0) | 16 (61.5) | |||
| - 1–3 mg/kg | 5 (71.4) | 1 (100.0) | 12 (75.0) | |||
| - 10 mg/kg | 2 (28.6) | 0 (0.0) | 4 (25.0) | |||
| Nivolumab | 2 (50.0) | 7 (58.3) | 23 (57.5) | |||
| - 3 mg/kg | 2 (100.0) | 7 (100.0) | 23 (100.0) | |||
| Pembrolizumab | 2 (50.0) | 3 (100.0) | 13 (61.9) | |||
| - 2 mg/kg | 1 (50.0) | 3 (100.0) | 9 (69.2) | |||
| - 3 mg/kg | 1 (50.0) | 0 (0.0) | 4 (30.8) | |||
| Number of ICI administration before onset, | 7 (38.9) | 7 (43.8) | 39 (47.6) | |||
| Median, [IQR] | 2 [2–5] | 6 [5–12] | 3 [1–7] | |||
| [min-max] | [1–7] | [2–12] | [1–31] | |||
| Time to irAE onset, days: | 5 (27.8) | 8 (50.0) | 39 (47.6) | |||
| Median, [IQR] | 21 [21–98] | 77 [59–153] | 55 [21–98] | |||
| [min-max] | [21–131] | [20–168] | [1–542] | |||
| Severe AE | 11 (68.8) | 16 (88.9) | 7 (43.8) | 16 (100.0) | 47 (61.8) | 76 (92.7) |
| Death | 0 (0.0) | 18 (100.0) | 0 (0.0) | 16 (100.0) | 5 (6.1) | 82 (100.0) |
| Malignant neoplasm progression | 0 (0.0) | 18 (100.0) | 0 (0.0) | 16 (100.0) | 1 (1.2) | 82 (100.0) |
| Indications** | 13 (72.3) | 13 (81.25) | 70 (85.3) | |||
| Malignant melanoma | 10 (76.9) | 9 (69.2) | 42 (60.0) | |||
| Lung cancer | 2 (15.4) | 3 (23.1) | 17 (24.4) | |||
| Squamous cell carcinoma of head and neck | 1 (7.7) | 0 (0) | 4 (5.7) | |||
| Renal carcinoma | 0 (0.0) | 1 (7.7) | 3 (4.3) | |||
| Melanoma + Multiple Myeloma | 0 (0.0) | 0 (0.0) | 1 (1.4) | |||
| Multiple Myeloma | 0 (0.0) | 0 (0.0) | 1 (1.4) | |||
| Colon Cancer - Metastatic | 0 (0.0) | 0 (0.0) | 1 (1.4) | |||
| T-Cell Lymphoma | 0 (0.0) | 0 (0.0) | 1 (1.4) | |||
| Concurrent irAE | 18 (100) | 16 (100) | 82 (100.0) | |||
| None (lone) | 7 (38.9) | 10 (62.5) | 30 (36.6) | |||
| Gastro-intestinal disorders (any) | 3 (16.7) | 2(12.5) | 9 (11.0) | |||
| - Colitis/ Enteritis / Diarrhea /Dehydration | 2 (11.1) | 2(12.5) | 7(8.5) | |||
| - Abdominal pain | 0 (0.0) | 1 (6.2) | 2 (2.4) | |||
| - Nausea/ Vomiting | 0 (0.0) | 1 (6.2) | 1 (1.2) | |||
| - Hepatic disorder | 1 (5.6) | 0 (0) | 1 (1.2) | |||
| Endocrino-metabolic disorders (any) | 3 (16.7) | 2 (12.5) | 7 (8.5) | |||
| - Fever | 1 (5.6) | 1 (6.2) | 3 (3.7) | |||
| - Thyroid disorders | 1 (5.6) | 0 (0) | 2 (2.4) | |||
| - Potassium imbalance | 0 (0.0) | 1 (6.2) | 1 (1.2) | |||
| - Adrenal insufficiency | 1 (5.6) | 0 (0) | 1 (1.2) | |||
| - Hypophysitis | 0 (0.0) | 1 (6.2) | 1 (1.2) | |||
| Dermatologic and Rheumatologic conditions (any) | 4 (22.2) | 4 (25.0) | 23 (28.0) | |||
| - Arthralgia/ Joint stiffness/ Arteritis | 2 (11.1) | 3 (18.8) | 9 (11.0) | |||
| - Rash / Purpura | 0 (0.0) | 0 (0) | 5 (6.1) | |||
| - Cutaneous vasculitis /Dermatitis | 0 (0.0) | 0 (0) | 4 (4.9) | |||
| - Skin discoloration/ Vitiligo | 0 (0.0) | 0 (0) | 3 (3.7) | |||
| - Myositis / Myasthenia gravis / Other | 2 (11.1) | 1 (6.2) | 3 (3.7) | |||
| - Pruritus | 0 (0.0) | 1 (6.2) | 1 (1.2) | |||
| - Skin ulcer | 0 (0.0) | 0 (0) | 1 (1.2) | |||
| - Skin infection | 0 (0.0) | 0 (0) | 1 (1.2) | |||
| Neurologic conditions (any) | 4 (22.2) | 1 (6.2) | 15 (18.3) | |||
| - Cerebral vasculitis | 0 (0.0) | 0 (0) | 4 (4.9) | |||
| - Ataxia/ Gait disturbance/ Vertigo | 0 (0.0) | 0 (0) | 4 (4.9) | |||
| - Headache | 3 (16.7) | 0 (0) | 3 (3.7) | |||
| - Decreased level of consciousness | 0 (0.0) | 0 (0) | 2 (2.4) | |||
| - Stoke (ischemic or hemorrhagic) | 0 (0.0) | 0 (0.0) | 2 (2.4) | |||
| - Encephalitis /meningitis | 0 (0.0) | 0 (0.0) | 2 (2.4) | |||
| - Hypoacousis | 0 (0.0) | 1 (6.2) | 1 (1.2) | |||
| - Unspecified neurologic disorder | 1 (5.6) | 0 (0.0) | 1 (1.2) | |||
| Ophthalmic conditions(any) | 5 (27.8) | 1 (6.2) | 10 (12.2) | |||
| - Blindness / impaired vision | 5 (27.8) | 1 (6.2) | 7 (8.5) | |||
| - Retinal hemorrhage/ retinal vasculitis | 1 (5.6) | 0 (0.0) | 2 (2.4) | |||
| - Optic neuritis | 1 (5.6) | 0 (0.0) | 1 (1.2) | |||
| - Diplopia | 1 (5.6) | 0 (0.0) | 1 (1.2) | |||
| - Ptosis | 1 (5.6) | 0 (0.0) | 1 (1.2) | |||
| - Uveitis | 0 (0.0) | 0 (0.0) | 1 (1.2) | |||
| Pulmonary conditions (any) | 1 (5.6) | 0 (0.0) | 5 (6.1) | |||
| - Pneumonia/ Pneumonitis | 1 (5.6) | 0 (0.0) | 4(4.9) | |||
| - Interstitial lung disease | 0 (0.0) | 0 (0.0) | 1 (1.2) | |||
| Hematologic conditions (any) | 1 (5.6) | 0 (0.0) | 6(7.3) | |||
| - Cytopenia | 1 (5.6) | 0 (0.0) | 3 (3.7) | |||
| - Anemia | 0 (0.0) | 0 (0.0) | 2 (2.4) | |||
| - Coagulopathy | 0 (0.0) | 0 (0.0) | 1 (1.2) | |||
| - Serum sickness syndrome | 0 (0.0) | 0 (0.0) | 1 (1.2) | |||
| Cardiac-vascular conditions (any) | 0 (0.0) | 0 (0.0) | 3 (3.7) | |||
| - Myocarditis | 0 (0.0) | 0 (0.0) | 1 (1.2) | |||
| - Myocardial infarction | 0 (0.0) | 0 (0.0) | 1 (1.2) | |||
| - Cardiac arrest | 0 (0.0) | 0 (0.0) | 1 (1.2) | |||
| - Deep vein thrombosis | 0 (0.0) | 0 (0.0) | 1 (1.2) | |||
Other concomitant reported suspected medications for vasculitis were allopurinol (n: 1), amoxicillinclavulanic acid (n: 1), bevacizumab (n: 1), ceritinib (n: 1), cisplatin (n: 1), dexamethasone (n: 1), duloxetine (n: 1), levothyroxine (n: 1), mupirocin (n: 1), paracetamol (n: 1), pemetrexed (n: 1), pomalidomide (n: 1), telmisartan (n: 1), temozolomide (n: 1), vemurafenib (n: 1), and unspecified drugs (n: 2).
Other concomitant reported suspected medications for temporal arteritis were bevacizumab (n: 1), duloxetine (n: 1), paracetamol (n: 1), temozolomide (n: 1), and vemurafenib (n: 1).
Of the 42 melanoma patients with ICI-associated vasculitis, 11 were treated with anti-CTLA-4 monotherapy, 21 with anti-PD-1 or anti-PD-L1 monotherapy, and 10 with combination of an anti-CTLA-4 plus an anti-PD-1 or an anti-PD-L1 therapy. All 17 vasculitis cases associated with ICI in lung cancer patients were treated with anti-PD-1 or anti-PD-L1 monotherapy.
Abbreviations: CTLA-4, cytotoxic T-lymphocyte-associated protein 4; ICI, immune checkpoint inhibitor; IQR, interquartile range; irAE, immune related adverse event; [min-max], minimum-maximum; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1; SD, standard deviation