Potential Benefit of Rituximab in Rhupus Patients From a Single-Center

Abstract

Background: Rhupus syndrome is better characterized, but uncertainties remain, and therapeutic management must be defined. The objective was to analyze therapeutic procedures with a focus on biologic disease-modifying antirheumatic drugs (bDMARDs). Methods:This 10-year medical records review was based on diagnosis codes (rheumatoid arthritis [RA] and systemic lupus erythematosus [SLE]) and biological data (anti-CCP testing, anti-dsDNA, and anti-RNP antibodies). Patients fulfilling 2010 ACR/EULAR and 2012 SLICC and/or 2019 ACR/ EULAR classification criteria for RA and SLE, respectively, were included.Results: Sixteen patients were identified. Rheumatoid arthritis most often preceded rhupus, with predominant articular pattern; 11 of them had erosive arthropathy. Skin involvement was the most frequent associated manifestation (n = 12). Serious events were reported, including active glomerulonephritis (n = 3), ischemic stroke (n = 1), and myocardial infarction (n = 1). Immunological profiles showed positivity for antinuclear (n = 16), anti-dsDNA (n = 9), and anti-CCP (n = 9). Ten patients required bDMARDs. All types of RA-approved bDMARDs were used. Abatacept was considered effective in 3 of the 4 patients, with 1 primary failure, 1 secondary escape, and 2 therapeutic maintenances, whereas primary or secondary failure was observed under tocilizimub and TNF-blocking agents. Rituximab was the most prescribed (n = 9) and the most effective with a sustained response in 6 patients. Conclusions:In rhupus refractory to conventional treatment, T or B lymphocytes targeted therapies, and particularly rituximab, seem to be a relevant therapeutic option unlike anticytokine biologics.

Lupus With Erosive Arthritis: A Singular Joint Phenotype of Lupus or Rhupus?

“…Moreover, other studies have shown that, although the presence of ultrasound-detected erosions is not specific to RA, larger erosions in selected joints are highly specific to RA 4 . In our work, we applied the European Alliance of Associations for Rheumatology definition of erosive disease 5 . Furthermore, the application of cluster analysis to better characterize SLE phenotypes revealed that EA was located in a cluster including anticitrullinated protein antibodies (ACPAs) and anticarbamylated protein antibodies 6 .…”

“…In this respect, whereas several preclinical works demonstrated the key role of IL-6 in the pathophysiology of several connective tissue disease, and early studies reported encouraging results with IL-6 inhibitors in these conditions, targeting IL-6–mediated signaling in SLE myositis and primary Sjögren syndrome did not show superiority in clinical responses versus placebo, except for a potentially beneficial effect of tocilizumab on preservation of lung function in systemic sclerosis–associated interstitial lung disease 9 . In the same way, a failure of tocilizumab was also observed in 2 and 8 patients who received this drug in our series of rhupus and RA/systemic sclerosis overlap syndrome, respectively 5,10 . Thus, until sets of biomarkers associated with particular involvement or predictive of treatment response become available, rather than trying to attribute all the manifestations, including EA, to the same disease, it is preferable, in our opinion, to consider overlapping syndromes as real entities for which it is more relevant to propose therapies having shown their effectiveness in both components of the syndrome.…”

“…4 In our work, we applied the European Alliance of Associations for Rheumatology definition of erosive disease. 5 Furthermore, the application of cluster analysis to better characterize SLE phenotypes revealed that EA was located in a cluster including anticitrullinated protein antibodies (ACPAs) and anticarbamylated protein antibodies. 6 Both autoantibodies belong to the family of anti-modified protein antibodies, which is one of the hallmarks of RA.…”

Lupus Arthropathy

“…After reading the article of Rottenberg et al, 1 we found that lupus arthropathy (LA) has been going through a process of conceptual evolution since the first classification criteria for the disease. The misconception that the presence of articular erosion would mark an overlap between systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) still causes many colleagues to attribute severe LA to rhupus 2 .…”

“…Understanding this evolution (Table) is essential for further research to identify early which SLE patients are at greater risk for the development of Jaccoud-type deformities and those with the worst joint prognosis that should be treated similar to RA patients. Interestingly, we would like to know if Rottenberg et al 1 have tried tocilizumab to manage some of those patients because the identification of interleukin 6 as a possible biomarker for aggressive LA deformities may signify that this drug may be a good choice for arthritis of both diseases 9 . Furthermore, other biomarkers, such as BLyS (B lymphocyte stimulator) and the presence of type I interferon gene signature, 10 may indicate patients with arthritis who, regardless of whether they meet the criteria for RA, SLE, or both, may benefit from new available therapies.…”