RSLV-132: Help for Recalcitrant SLE?

First new SLE drug in 40 years currently under investigation

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By Howard R. Smith, MD

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A 69-year-old woman presented to Cleveland Clinic’s Lupus Clinic with a diagnosis of subacute cutaneous lupus erythematosus (SCLE). She had initially presented to an outside physician with red, blotchy, pruritic skin lesions on her chest that were spreading but not overly distressing. Her initial treatment was a topical preparation of unknown composition, but her skin did not improve.

An outside skin biopsy led to a diagnosis of and treatment for spongiotic dermatitis, but her condition continued to worsen. Another biopsy led to a diagnosis of and treatment for pityriasis rosea. The lesions continued to spread, leading to a third skin biopsy and a diagnosis of SCLE.

Oral prednisone brought some relief, but her physician transitioned her to oral hydroxychloroquine (Plaquenil®) to avoid long-term steroid use. However, she discontinued use after two months due to gastrointestinal side effects. Another low-dose course of prednisone was attempted.

When the patient presented to us, I changed her diagnosis to systemic lupus erythematosus (SLE) based on a skin biopsy as well as the presence of arthritis, rash and blood tests confirming positive antinuclear antibodies and extractable nuclear antigens.

Comorbidities make treatment a challenge

Choosing the right treatment for this patient was complicated to say the least. She has two important comorbidities that limit the use of immunosuppressive therapy — congenital asplenia, which predisposes her to septicemia, and autoimmune hepatitis with cirrhosis of unknown etiology. She also has sicca, osteoarthritis, Raynaud syndrome, alopecia and photosensitivity.

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I initially treated her with dapsone, but that exacerbated her liver problems.

Prednisone again brought her some relief, but she couldn’t be tapered below 20 mg without a flare. Maintaining her at a higher dosage is contraindicated due to her predisposition to infections.

Restarting the patient on low-dose (25 mg) dapsone has brought her some relief, but I continue to monitor her liver function tests closely. She continues to suffer with classic annular-shaped lesions of 3 to 4 inches in diameter on her chest, face and arms (Figures 1, 2).

Phase 2 trial examines first investigational SLE drug in nearly 40 years

We clearly need solutions for complex SLE patients who do not respond to current therapies. Perhaps one is on the horizon; I am currently principal site investigator for a phase 2 study of one of the first investigational drugs available for SLE patients in nearly 40 years.

RSLV-132 is novel; nothing like it has been created before. RSLV-132 (Resolve Therapeutics, Seattle, WA) is an Fc-fusion protein consisting of human RNase attached to the Fc portion of human IgG. The drug is designed to enzymatically digest the RNA contained in immune complexes, thereby preventing the chronic activation of interferon and inflammation characteristic of SLE. This contrasts with immunosuppressive therapy, which can have many complications.

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The main focus of this double-blind, multisite study is the extent of skin involvement in SLE patients and how it responds over the course of the study. RSLV-132 is not a first-line treatment, but it may be particularly promising for some of the 60 to 80 percent of lupus patients with skin manifestations.

For additional information and to refer patients to the study, please call 216- 444-4555. We hope to recruit and ultimately help patients with significant skin disease who have failed other therapies.

Dr. Smith is a staff rheumatologist and Director of the Lupus Clinic.