To try to make headway in this field, it is important to scrutinize the scientific evidence in this regard. TNF is clearly overexpressed in SLE. High levels of TNF have been found in SLE sera, where they closely correlate with SLE disease activity.4 Despite a concomitant increase in soluble TNF receptors, the increased TNF is bioactive.5 Furthermore, at the level of inflamed tissue, TNF expression has been found in lupus skin lesions and in inflamed renal tissue of patients with lupus nephritis, where it also correlates with disease activity (see “TNF and Organ Inflammation,” p. 18).6,7 In several lupus mouse models, including the MRL/lpr mouse, in particular, TNF significantly increases over time, in parallel with developing organ inflammation. Even NZB/W mice, which otherwise lack TNF, have increased TNF in their severely inflamed kidneys in the end. In some mouse model systems, attempts at TNF blockade have actually led to improvement in murine lupus.
Finally, the limited clinical experience with TNF blockade in SLE suggests benefits for inflammatory organ disease, including lupus nephritis, lupus arthritis, skin lupus, interstitial lung disease, and haemophagocytic syndrome.1,8 Of the first 10 patients treated in Vienna, all of whom were primarily treated with an induction regimen of four infusions of infliximab, eight had lupus nephritis and three had lupus arthritis (one had both). Two additional patients from Belgium and the U.K., with lupus nephritis and arthritis, and interstitial lung disease, respectively, were treated with somewhat different regimens.1 In addition, there are published case reports and small case series including 14 patients with lupus nephritis, 20 with lupus arthritis, and three with haemophagocytic syndromes.9-11
There appear to be significant differences in the response patterns of different organ manifestations in that effects were short-lived in lupus arthritis, comparable to the situation in RA, but long lasting (over years) in lupus nephritis and possibly in manifestations in other organs. Regarding treatment options, if these findings are confirmed, they would suggest the need for continuous therapy for lupus arthritis, but, much more favorably, only induction therapy for lupus nephritis (see Figure 1, below).