Association between Monoclonal Gammopathy and Rheumatoid Arthritis: A National Inpatient Sample (NIS) Study

Introduction: Monoclonal gammopathy (MG) is a spectrum of conditions including monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). MM is the second most common hematologic malignancy. Despite advances in the treatment of MM it remains an incurable disease that accounts for > 80 000 deaths annually worldwide. Many etiologies for myelomagenesis have been postulated. One theory suggests that chronic antigen stimulation from rheumatologic conditions can increase the risk of MG. Numerous studies have reported an increased risk of MG and other lymphoproliferative disorders in patients with systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS). However, the association between rheumatoid arthritis (RA) and MG is controversial as conflicting results have been reported. Case control studies have described an increased risk of RA but this finding was not corroborated in a subsequent meta-analysis. We used the national inpatient sample (NIS) database to explore the association of RA with MGUS and MM.

Methods: The NIS is a validated database derived from discharge billing information which provides a sample of all non-federal hospital discharges in the Unites States. We identified adult patients with discharge diagnosis codes for MGUS (ICD-9 273.1), MM (ICD-9 203.0), RA (ICD-9 714.0), SLE (ICD-9 710.0) and SS (ICD-9 710.2) from 2014. Demographic data such as age, sex and race were also obtained. Multiple logistic regressions were used to analyze data for association of RA with MGUS and MM after adjusting for age, gender, race and other rheumatic diseases. Statistical analysis was performed with STATA 14.

Results: A total of 7,071,762 discharges were analyzed. There were 20,066 hospitalized adults with discharge diagnosis codes for MM and 6,433 patients with a discharge diagnosis of MGUS. The prevalence of RA in patients with MGUS is 5.1% (p<0.001) and the prevalence of RA in patients with MM is 1.6 % (p=0.92). By logistic regression MGUS was associated with RA (OR 2.04, CI 1.80 - 2.32, p<0.0001) when adjusted for age, gender, race, SLE and SS. However, logistic regression did not show a significant association between MM and RA when adjusted for the same variables (OR 1.05, CI 0.95-1.15, p=0.23). MGUS was significantly associated with SS (OR 4.4, CI 3.29-5.90, p<0.001) and SLE (OR 1.9, CI 1.44-2.43, p<0.001) when adjusted for variables.

Discussion: Our review of the NIS database found a significant association between rheumatologic disorders (RA, SLE and SS) and MGUS. These results are in concordance with previous retrospective studies. However, we did not find a significant relationship between RA and MM. There is known to be a high prevalence of MGUS in the general population, the clinical significance of which is being debated. The association between RA and MGUS that our study found may be due to a selection bias as patients with rheumatic conditions such as RA are tested more frequently for MGUS than the general population.