An Update on Treatment Options for Systemic Lupus

Oct 29, 2019

While significant advances have been made in the treatment of systemic lupus erythematosus (SLE), the highly variable manifestations of the disease make treatment difficult.

While significant advances have been made in the treatment of systemic lupus erythematosus (SLE), the highly variable manifestations of the disease make treatment difficult. Today, SLE patients have increased survival and reduced rates of end-stage renal disease. Writing in a review published in BMJ Lupus Science & Medicine, Antonis Fanouriakis and George Bertsias point out that treatment remains less than optimal. They review changing paradigms in lupus treatment focusing on unmet needs and revisiting established therapies. In this slideshow, we highlight takeaways from the review.

References:

Antonis Fanouriakis and George Bertsias. "Changing paradigms in the treatment of systemic lupus erythematosus." Lupus Science & Medicine. (www.lupus.bmj.com/content/6/1/e000310).

Hydroxychloroquine (HCQ) remains the first line treatment for SLE even though high quality evidence is lacking. HCQ is known to have beneficial effects in SLE however adherence to treatment appears to be suboptimal.

In addition to questionable efficacy, recent advancements in screening have revealed more HCQ-induced retinal toxicity among chronic users. The authors point out that the data suggests that under dosing may be occurring while adherence is low and warn that these discoveries may lead to even higher doses and even higher risk for ocular toxicity.

While conceding that HCQ treatment is of high value, the authors suggest that the dose should not exceed 5mg/kg ideal body weight in conjunction with regular high quality eye exams. Research will be needed looking at HCQ dose, blood levels and efficacy. Finally, quinacrine may be used as an alternative to HCQ when skin manifestations are present.

Like HCQ, glucocorticoids (GC) are widely used in SLE even though limited rigorous evidence exists. While using GCs in the acute control of lupus is proven, long-term use can be problematic due to irreversible organ damage accrual.

In an effort to use less GCs, combination therapy with rituximab and mycophenolate mofetil was studied without oral steroids and lead to a 86% remission rate. A recent Spanish study showed that lower doses of GCs could be used in conjunction with frequent use of HCQ and immunosuppressants sparing SLE patients from the effects of long-term steroid use.

The authors believe that GC use in SLE should be prescribed with lower cumulative doses in mind and even discontinued if possible after acute lupus flares. Clinicians should aim to prescribe prednisone at 0.5-0.6 mg/kg/day to start, and no higher than 7.5g/day after 6 months.

Immunosuppressant (IS) drugs are very useful in SLE allowing for more rapid and successful tapering of GCs. The authors point out that different IS drugs work better depending on which organ system is most affected by SLE.

Recent randomized evidence showed a 71.2% remission rate for extrarenal SLE when mycophenolate sodium and azathioprine (AZA) were used in combination with GCs and significantly reduced the occurrence of flares compared to azathioprine alone. The authors recommend MTX for arthritis and skin involvement, azathioprine or cyclosporine for hematological disease or in pregnancy and cyclophosphamide for severe disease or rescue therapy.

First line therapy for lupus nephropathy consists of mycophenolate mofetil (MMF) and low dose cyclophosphamide for induction and then either MMF or AZA for maintenance. More recent studies may suggest that Calcineurin inhibitors (CNI) may be equal to or better than the previously mentioned first line drugs. Unfortunately these studies were limited to an Asian population and had only short-term follow up.

Without strong evidence the authors recommend CNIs for patients with proliferative or membranous nephropathy refractory to initial treatment. For refractory patients with predominant nephritic disease they favor high-dose intravenous cyclophosphamide or rituximab.

Belimumab has been shown in observational studies to be effective in reducing SLE disease activity and flare rate as well as in allowing dose reductions for GCs. It appears that patients with high disease activity and GC dependence will benefit most from treatment with belimumab. The authors do not initiate belimumab treatment without documented prior failure to at least on IS drug. They further suggest that belimumab should be offered as add-on treatment in patients with extrarenal manifestations of moderate severity, and optimal responses should be awaited at 4–6 months of therapy. The role of rituximab is yet to be determined.

Goals of treatment in SLE should include in all patients:

1) Control of disease activity.
2) Prevention of disease flares.
3) Minimization of irreversible damage accrual.
4) Avoidance of drug toxicity.
5) Improvement of patient quality of life.

The authors believe that these goals are best achieved through a strategic plan tailored to each patient.

Comorbidities should be avoided such as through prevention of infections with appropriate vaccination. Traditional risk factors for cardiovascular disease should be treated as needed as well as SLE specific factors such as anti-phospholipid (aPL) antibodies and GC use. Aspirin should be given to aPL patients and calcium and vitamin D should be given to patients on GC therapy.

In the future better SLE drug trial designs are needed. Other future advances should include:

1) A definition of a universally accepted level of minimal disease activity, if remission is unachievable.
2) Real-life trials comparing low versus traditional GC regimens, as well as different IS drugs for similar manifestations.
3) Prospective studies exploring optimal duration of treatment and opportunities for drug discontinuation.
4) Research on biomarkers and prognostic factors related to response to different therapies.