IVIG Eases Pain in Sjögren Disease Sensory Neuropathy

In patients with Sjögren disease who experience painful sensory neuropathies, use of intravenous immunoglobulins (IVIG) resulted in significantly improved pain and less disability compared to placebo, according to a randomized controlled trial presented by Jacques-Eric Gottenberg, MD, PhD, a professor of rheumatology at Strasbourg University Hospital in France, at the International Symposium on Sjögren’s Disease in Paris, France.“Painful sensory neuropathy is one of the most frustrating manifestations of Sjögren’s disease. Rheumatologists and neurologists have used IVIG for years based largely on case reports, retrospective series, and expert opinion. The TINISS [Traitement par Immunoglobulines Veineuses des Neuropathies Sensorielles du syndrome de Sjögren] trial provides the first randomized placebo-controlled evidence supporting IVIG in this indication,” Chadwick R. Johr, MD, director of Penn Sjögren’s Center and an associate professor of clinical medicine in rheumatology at the University of Pennsylvania Perelman School of Medicine, Philadelphia, told Medscape Medical News. Johr was not involved in the research.Prior epidemiologic research has shown the prevalence of peripheral nervous system involvement to be about 15% in patients with primary Sjögren disease. Results with IVIG have been mixed, as shown in one retrospective study of 19 patients, but closer examination of the results suggested that the clinical phenotype influenced the success of outcomes. Five patients with sensorimotor and four with nonataxic sensory phenotypes all improved or stabilized, but the results for nine patients with ataxic sensory phenotype were mixed, including four whose symptoms worsened.Gottenberg and his colleagues therefore designed the prospective randomized TINISS study, and enrolled 22 adults, aged 18-80 years, from 12 French university hospitals who had Sjögren disease and clinically defined painful sensory or sensorimotor neuropathy confirmed by electromyography. Twelve participants were randomly assigned to receive IVIG, and 10 were assigned to receive placebo. The final analysis included 12 in the intervention arm and eight in the placebo arm after one withdrew before infusion due to lung cancer and another did not have an evaluation of the primary endpoint.Most of the participants were women (80%). Participants in the IVIG group were a median 67 years old, had Sjögren symptoms for a median 6.8 years, and had been diagnosed for a median 0.9 years. In the placebo arm, participants were a median 73 years old, had symptoms for a median 9.4 years, and had been diagnosed for a median 4.7 years. The median time since first neuropathic symptoms in the IVIG arm (5 years) was similar to that in the placebo arm (6 years), and pain scale rating was similar between the groups (6.0 and 6.5, respectively).The primary endpoint was the proportion of patients who achieved at least a 20% improvement from baseline at week 11 in either the Rasch-built Overall Disability Scale or the 0-10 numerical pain rating scale. Six patients in the IVIG group and one patient in the placebo group met the primary endpoint, yielding a probability of 96.5% superiority of the IVIG treatment.The change from baseline on the numerical pain rating scale was a median -1.90 in the IVIG group compared to 1.45 in the placebo group, yielding an 86.1% probability of superiority in change between the groups. In addition, on a clinician-rated scale (0-12) of functional limitation from neuropathy in the arms and legs, change from baseline was a median -0.15 in the IVIG group and 1.17 in the placebo group, yielding an 88.4% probability of superiority.There were two serious adverse events in each treatment arm, none of which were considered to be treatment-related.The research was funded by CSL Behring. Gottenberg reported consulting, advising, and/or receiving speaking honoraria from AbbVie, Argenx, Bristol Myers Squibb, CSL Behring, Eli Lilly, Galapagos, Gilead, Johnson & Johnson, MSD, Novartis, Pfizer, Sanofi, and UCB, and research support from CSL Behring. Johr reported advising/consulting work with Novartis, Sobi, Amgen, and Bristol Myers Squibb. Tara Haelle has been an independent science/health journalist for over 15 years, with work appearing in over two dozen trade and consumer publications. She is author of Vaccination Investigation: The History and Science of Vaccines and The Informed Parent: A Science-Based Guide to the First Four Years. Tara is the Public Health Beat Leader for the Association of Health Care Journalists, where she develops resources to help other journalists report on medical studies and public health. She is based in Dallas.