Extra-Articular Manifestations of RA Remain a Concern

CHICAGO – Extra-articular manifestations of rheumatoid arthritis still affect more than 40% of patients, and although the incidence of some severe manifestations, such as vasculitis, has declined over time, the incidence of others has increased, and many of these manifestations can adversely affect prognosis and increase mortality.

The 10-year cumulative incidence for all extra-articular manifestations of RA was nearly 50% in a cohort of 463 patients with incident RA in 1995-2007 who were followed through the end of 2008, which is similar to the 46% incidence in a similar cohort of 197 patients who were followed from 1985 to 1994. However, severe manifestations – including ocular disease and vasculitis – occurred in about 7% and 9% of patients in the cohorts, respectively, reported Dr. Eric Matteson at a symposium sponsored by the American College of Rheumatology.

The findings, which were published online April 1 in the Journal of Rheumatology, are from a follow-up of a retrospective, longitudinal, population-based study involving the first cohort. Both cohorts included residents from a single county in Minnesota who were at least 18 years of age and who met at least four of the American College of Rheumatology criteria for RA (J. Rheumatol. 2011 April 1 [doi:10.3899/jrheum.101133]).

The most striking finding was the reduction in the incidence of vasculitis, which affected 3.6% of patients in the earlier cohort, but only 0.6% in the recent cohort, said Dr. Matteson, chair of rheumatology at the Mayo Clinic in Rochester, Minn.

Episcleritis, neuropathy, xerostomia, cervical myelopathy, pulmonary fibrosis, Sjögren’s syndrome, and keratoconjunctivitis sicca (KCS) also occurred less often in the later cohort, whereas subcutaneous nodules, pleuritis, pericarditis, and bronchiolitis obliterans-organizing pneumonia (BOOP) all occurred slightly more often in the later cohort.

The study also showed that the occurrence of a second extra-articular manifestation was reduced significantly in the second cohort (hazard ratio, 0.5), and that having any extra-articular manifestation was significantly associated with an increased risk of mortality (HR, 2.0). No additional increase in mortality risk was seen with severe or second extra-articular manifestations, Dr. Matteson noted.

The reasons for the decline in severe manifestations and second manifestations likely include more aggressive treatment strategies – and perhaps the use of biologics – in recent years; more vigorous disease control throughout the course of disease; and possibly secular trends, such as reduced smoking and other as-yet unidentified factors, he said.

Predictors of extra-articular manifestations include smoking, erosive severe joint disease, the need for disease-modifying antirheumatic drugs or biologic response modifiers, and seropositivity for ANA (antinuclear antibodies) or pANCA (perinuclear antineutrophil cytoplasmic antibody). Other genetic or environmental factors that are not yet fully understood might also contribute, he said.

Management of extra-articular manifestations should be guided by the organ system involved, but steroids are a mainstay of treatment. Treatments that control synovitis, including NSAIDs, are often effective as well.

For severe manifestations, treatment with glucocorticoids is often needed for at least 2 months. The role of pulse glucocorticoids, although popular, has not been established by randomized, controlled studies, Dr. Matteson said.

In fact, there is a dearth of data regarding treatment of these manifestations in general, he said, noting that cytotoxic drugs are sometimes used, particularly in patients with vasculitis or inflammatory eye disease, and that the role of newer agents – such as anti–B-cell therapy, abatacept, and tumor necrosis factor antagonists – is unclear, as there is anecdotal evidence of both successful and detrimental effects.

Dr. Matteson disclosed that he has received grant support from, and/or served as an investigator or consultant for Amgen, Biogen-IDEC, Centocor, Genentech, Hoffmann-La Roche, Human Genome Sciences, Mayo Foundation, National Institutes of Health, Novartis, Pfizer, and UCB.