Immune Checkpoint Inhibitor Treatment Toxicity Risk in RA

Risk of Toxicity After Initiating Immune Checkpoint Inhibitor Treatment in Patients With Rheumatoid Arthritis

Elizaveta Efuni, MD; Samuel Cytryn, MD; Patrick Boland, MD; Timothy B. Niewold, MD; Anna Pavlick, DO; Jeffrey Weber, MD, PhD; Sabina Sandigursky, MD

Disclosures

J Clin Rheumatol. 2021;27(7):267-271.

Abstract and Introduction

Abstract

Introduction: Immune checkpoint inhibitors (ICIs) are increasingly used to treat advanced cancer. Rheumatoid arthritis (RA) is associated with an increased risk of malignancies; however, patients with RA have been excluded from ICI trials. In this study, we evaluated risk of toxicity after initiation of ICI treatment in RA patients.

Methods: We conducted a single-institution, medical records review analysis to assess the incidence of immune-related adverse events (irAEs) and autoimmune disease (AID) flares among patients with AIDs treated with ICIs from 2011 to 2018. A subgroup analysis for RA patients was performed with frequencies of irAEs and AID flares reported.

Results: Twenty-two patients with RA who were treated with ICI for malignancy were identified. At the time of ICI initiation, 86% had inactive RA disease activity. Immune-related adverse events occurred in 7 (32%) of patients, with 2 (9%) developing grade 3 (i.e., severe) irAEs. Immune checkpoint inhibitors were temporarily discontinued because of irAEs in 5 patients (23%), and permanently in 1 patient. Rheumatoid arthritis flares occurred in 12 patients (55%). Of those, 10 (83%) received oral corticosteroids with an adequate treatment response.

Conclusions:Our analysis suggests that irAEs following ICI treatment are not increased among RA patients compared with other cancer patients.

Abstract and Introduction
Patients and Methods
Results
Discussion
References

Table 1. Rheumatoid Arthritis Patient Characteristics: Demographics, Malignancy, ICI Therapy (n = 22)
	n (%)
Age at cancer diagnosis, median, y	67
Male	6 (27)
Female	16 (73)
RA disease duration prior to start of ICI, y
>5 y	10 (45)
<5 y	2 (9)
Duration unknown	10 (45)
Other AID present	7 (32)
Polymyalgia rheumatica	2 (9)
Chronic inflammatory demyelinating polyneuropathy	1 (5)
Psoriasis	1 (5)
Sjögren/sicca^a	3 (14)
Ulcerative colitis	1 (5)
Sarcoidosis^a	1 (5)
Psoriatic arthritis^a	1 (5)
Disease activity
Inactive	19 (86)
Active	3 (14)
Immunomodulatory therapy at start of ICI^b
No treatment for AID	6 (27)
Systemic corticosteroids	12 (55)
Hydroxychloroquine	3 (14)
Methotrexate	7 (32)
Etanercept	1 (5)
Sulfasalazine	2 (9)
Intravenous immunoglobulin	1 (1)
Prednisone equivalent dose, mg/d
>11–20	2 (9)
5–10	7 (32)
<5	3 (14)
Malignancy type
Melanoma	7 (32)
Lung adenocarcinoma	4 (18)
Squamous cell carcinoma of lung	3 (14)
Merkel cell carcinoma	2 (9)
Ovarian adenocarcinoma	1 (5)
Squamous cell carcinoma of head and neck	2 (9)
Urothelial carcinoma	1 (5)
Renal cell carcinoma	1 (5)
Hodgkin lymphoma	1 (5)
Malignancy disease duration prior to ICI, median, mo	18
Melanoma disease duration prior to ICI, median, mo	34
ICI used
Ipilimumab	5 (23)
Nivolumab	9 (41)
Pembrolizumab	13 (59)

^aOne patient had inflammatory arthritis, diagnosed as seronegative RA/psoriatic arthritis overlap, sicca syndrome, and sarcoidosis.
^bSeven patients received more than 1 immunomodulatory agent simultaneously (i.e., methotrexate/hydroxychloroquine, prednisone/methotrexate).

Table 2. IrAEs and RA Flares Among RA Patients Receiving ICI Therapy (n = 22)
Characteristic	n (%)
Developed irAEs	7 (32)
Did not develop irAEs	15 (68)
Types of irAE
Dermatitis	4 (18)
Colitis	3 (14)
Hepatitis	1 (5)
Time to irAE, median (IQR), mo
Colitis	3 (3.5)
Dermatitis	1 (8.5)
All irAEs	1 (3.5)
Severity of irAEs
Grade 1–2 irAEs	5 (23)
Grade 3 irAEs^a	2 (9)
irAE management	n = 7
Systemic corticosteroids	4 (57)
Topical steroids/supportive treatment	4 (57)
ICI use at time of irAE
Permanently discontinued	1 (5)
Temporarily discontinued	5 (23)
ICI continued after irAE	1 (5)
RA flares
Developed a flare	12 (55)
Did not develop a flare	10 (45)
Time to flare, median (IQR), mo	1 (1.75)
Flare treatment	n = 12
Oral prednisone	10 (83)
NSAIDs	2 (17)
Methotrexate^b	1 (8)
Sulfasalazine^b	1 (8)
Prednisone equivalent dose for flare, mg/d
>40 mg	4 (33)
<20 mg	6 (50)
ICI use at time of flare
Permanently discontinued	2 (9)
Temporarily discontinued	1 (5)
ICI continued	9 (41)