Background/Purpose: Previous studies suggest that steroid dose¹and rheumatoid factor positivity² impact cancer survival in checkpoint inhibitor (CI)-treated patients (with CI-associated hypophysitis, and in all-comers with non-small cell lung cancer patients respectively).  In this study we describe CI-associated arthritis phenotypes in patients enrolled in a CI registry, and measure the impact of phenotype, steroid dose, and serologic status on survival.

Methods: Patients referred to rheumatology at Hospital for Special Surgery (HSS) for CI-associated immune-related adverse events were enrolled in our registry.  Demographics, cancer types, treatment and outcomes, musculoskeletal findings, labs and serologies were collected prospectively.  We defined four categories of arthritis: (1) “small joint” swelling ± large joint involvement, (2) exclusively “large joint” swelling, (3) joint pain without joint swelling (“arthralgia”), and (4) polymyalgia rheumatica (“PMR”). For this analysis, we excluded patients with non-articular conditions, crystal disease, or mechanical disorders.  Distribution of continuous variables was assessed using the Shapiro-Wilk test and summarized as median [IQR]; categorical variables are summarized as frequencies.  Progression-free survival (PFS), measured from CI initiation until documented radiographic progression, is presented in Kaplan-Meier curves compared by 2-sided log rank test. Hazard ratios were estimated using Cox proportional hazards regression analysis.

Results: Of 50 registry patients enrolled between 5/1/18-4/1/19, 37 had articular complaints.  Median [IQR] age was 67 [59,77], 22 (59%) were female, 17 (49%) had a smoking history, 14 (38%) had metastatic melanoma and 25 (68%) received anti-PD-1/PD-L1 monotherapy (Table 1). Median time to symptom onset was 2.8 [0.9,12] months after CI initiation. 22 (59%) had small joint involvement, 5 (14%) large joint, 8 (22%) arthralgia and 2 (5%) PMR.  9 (24%) had concomitant enthesitis/tenosynovitis and 11 (31%) were RFand/or CCP positive.  The large joint phenotype was notable for prevalent combination CI (80%) and tenosynovitis (60%), high ESR of 90 [28,99], and no RF/CCP positivity. Overall, 17 (46%) patients required > 20mg prednisone, and 6 (16%) required a biologic DMARD (Figure 1). Overall median PFS was 100 [64,151] weeks, and did not differ between melanoma vs. non-melanoma, patients treated with >20mg vs. ≤20mg prednisone, RF/CCP pos vs. neg, or small joint vs. other phenotypes (Figure 2).

Conclusion: In our cohort, neither steroid dose nor seropositivity were associated with progression-free survival in CI-treated patients with symptomatic musculoskeletal syndromes. However, our findings are limited by the small size and heterogeneity of our cohort.

¹Faje A. Pituitary 2016; 19:82–92

²Toi Y et al. JAMA Oncol; Epub 12/27/18

ACR 2019 abstract Table 1

medications ACR 2019

ACR 2019 survival curves