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


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

In This Article

Patients and Methods

Using our institutional electronic medical record, we identified and collected clinicopathologic data of patients with preexisting AIDs who had been treated for a malignancy with ICIs ipilimumab, pembrolizumab, and nivolumab between April 1, 2011, and November 15, 2018. Eligible patients were older than 18 years, with documented AID diagnosis by International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes prior to initiation of ICI. Patients with asthma or hypothyroidism without evidence of autoimmune thyroiditis were excluded. Cancer diagnoses included melanoma (7 [32%]) and NSCLC (7 [32%]), as well as gynecologic, urologic, renal, and blood malignancies (Table 1). In total, we identified 246 patients who received ICIs and carried a preexisting AID diagnosis. After excluding patients who were diagnosed with AID processes after ICI initiation, as well as those with nonautoimmune thyroiditis and gout, 84 patients met eligibility criteria with AIDs including rheumatologic (40 [48%]), dermatologic (24 [29%]), endocrine (16 [19%]), gastrointestinal (14 [17%]), neurologic (5 [6%]), and hematologic diseases (1 [1%]). Of those, we identified 22 patients with a documented diagnosis of RA. The electronic record was reviewed for documentation of an RA diagnosis in accordance with the American College of Rheumatology 2010 criteria when such information was available (Figure). In cases where no American College of Rheumatology criteria data were available, the patient was categorized as having RA if a diagnosis was documented by a rheumatologist or an oncologist who was in communication with rheumatologist and was coded with an ICD-9 or ICD-10 code.


Sample recruitment and serologic characteristics.

Medical records review was conducted for each patient including outpatient and inpatient records, medication prescriptions, and documentation by treating oncologists and rheumatologists. Patients' RA was classified as active at the time of ICI initiation if (1) prior to receiving ICI, the patient exhibited symptoms of RA (joint pain, swelling, stiffness, and tenderness), and (2) the medication dose for RA was increased, or new medications to control RA were prescribed within 1 month prior to ICI initiation. Medications for RA were categorized as immunomodulatory if they were systemic corticosteroids, methotrexate, biologics (tumor necrosis factor α inhibitors, abatacept), hydroxychloroquine, sulfasalazine, and JAK inhibitors. Medications categorized as supportive (i.e., not immunosuppressive) included topical steroids, lotions, thyroid hormone replacement therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), and antidiarrheal medicines.

Primary outcomes included incidence of irAEs, and incidence of RA flares after ICI initiation, determined based on documentation by the treating oncologist and, when available, by a rheumatologist. The adverse reaction was categorized as an RA flare if there was documentation of synovitis by rheumatologist that was deemed to be a flare, or if the patient reported worsening pain and swelling in RA-affected joints documented by the treating oncologist. An adverse event was categorized as an irAE if the patient experienced de novo symptoms not consistent with their preexisting RA presentation (i.e., diarrhea, rash, other). Immune-related adverse events were classified by grade according to the Common Terminology Criteria for Adverse Events v5.0, with severe qualifying as grade 3 or greater. If an irAE (e.g., dermatitis) recurred in the same patient, it was counted as a new event. The number of events for common irAEs was reported as frequencies. Incidence could not be determined for these patients as this was a medical records review analysis, and time of exposure was not always clear. The secondary outcome was overall survival, defined as number of months from initiation of ICI treatment to date of death or most recent follow-up with a physician if date of death was unavailable. Descriptive statistics were used to summarize characteristics of our cohort, which were reported using percentages for categorical variables and medians for continuous variables with interquartile range (IQR) reported for AID flares and the most common irAEs. Data were analyzed using STATA software. Our study was approved by the institutional review board of New York University School of Medicine.