How would you treat active SLE with high level crithidia dsDNA abs and recurrent pleuritis with effusions still requiring corticosteroids despite combination therapy with full doses of mycophenolate, hydroxychloroquine, and Benlysta for over 6 months after no response to Saphnelo for 6 months?

There are no controlled trials of different therapies for treating refractory pleuritis in lupus as the primary manifestation. Due to refractory pleuritis being relatively uncommon, the trials of benlysta and anifrolumab did not have enough patients to assess response. In the literature, there are a number of case reports with success using high-dose steroids and cytoxan, plasmapheresis and sirolimus, IVIg, and rituximab. Although not tested that I can find, one might think that rilonacept and/or anakinra may be effective given their use for refractory pericarditis. If the pleural effusions are the only active component of their lupus, then pleurodesis could be considered in place of further escalation of immunosuppression. I have no eviden...

To add to Dr. @Dr. First Last's excellent answer:

Treatment-resistant, recurrent pleural effusions after such good combination therapies as these would be highly unusual. Though anti-dsDNA Crithidia is positive, this does not necessarily mean the effusions/pleuritis are due to SLE. I have patients with quite high anti-dsDNA's who are otherwise clinically quiescent.

A re-examination of the etiology of the effusions is important. Though Occam's razor would point toward SLE serositis, SLE patients can have other non-SLE problems going on.

In order not to miss anything, I'd want to consider redoing the workup with pleural effusion analysis (cytology, white count, total protein, ANA, C3, C4, cxs, cholesterol, LDH, glucose, etc), but also consider ...

First, confirm this is genuinely refractory lupus serositis and not a mimic before escalating immunosuppression.

Assuming active lupus serositis is confirmed, I would escalate to an alternative biologic rather than increasing glucocorticoids. Since full-dose MMF has already failed, I would argue that a mechanistic change is needed. I would also make sure that NSAIDs and colchicine have been optimized as adjuncts.

The most recent 2025 ACR SLE guidelines name IL-1 blockade as the panel's preferred biologic for predominant pleuropericarditis, but this is explanatory expert-consensus text rather than a separately graded recommendation, and it rests largely on weak, indirect evidence extrapolated from pericarditis and mixed polyserositis rather th...