No Quick Fix in Lupus: Long-Term Treatment Works Best

March 8, 2019

A recent study published in Arthritis & Rheumatology has demonstrated that belimumab is both safe and effective in patients with systemic lupus erythematosus and provides disease control over the long term.

A recent study published in Arthritis & Rheumatology has demonstrated that belimumab is both safe and effective in patients with systemic lupus erythematosus and provides disease control over the long term.

It has been previously demonstrated in phase two controlled trials that belimumab in addition to standard therapy was well tolerated in autoantibody-positive systemic lupus erythematosus (SLE) patients for up to 52 weeks. Subsequent investigations also proved the efficacy and safety of belimumab for up to seven years.

Dr. Daniel Wallace, M.D., and researches from multiple centers in the U.S. report on the remainder of follow-up out to 13 years for their phase III investigation into the long-term safety and efficacy of belimumab in SLE.

THE STUDY

GlaxoSmithKline conducted this multicenter, open label, continuation study looking at belimumab intravenous (IV) plus standard of care therapy in patients with SLE who responded to treatment during the phase II, double-blind study.

During phase three patients who previously received the placebo were started on 10mg/kg IV belimumab while those given belimumab during phase two continued on the drug. All patients in the continuation study received intravenous belimumab every four weeks until they withdrew from the study or they reached the end of the study.

Adverse events were recorded throughout follow-up and clinical laboratory studies were performed. Disease activity was determined utilizing the British Isles Lupus Assessment Group (BILAG) index, the combined Safety of Estrogens in Lupus National Assessment /Systemic Lupus Erythematosus Disease Activity Index (SLENA-SLEDAI), and the SLE responder index (SRI).

The population was analyzed for intention-to-treat with post hoc reporting of adverse events (AE) per 100 patient-years, SRI response among patients who withdrew and disease activity in patients on low dose prednisone.

298 (62.6%) of the original study participants entered the continuation study with 96 reaching the end of follow-up. Withdrawal due to lack of efficacy was rare. At years five, seven and 10, the percentages of patients remaining in the study were 70.1%, 60.1%, and 44.3%, respectively.

The portion of subjects reporting adverse events remained stable or decreased throughout the study. The most common AEs were: upper respiratory infections, sinusitis, urinary tract infection, and headache. The rate of serious infections and infestations remained steady from year 1 through year 11. The rate of malignant neoplasms excluding non-melanoma skin cancer was 0.6/100 patient-years.

The rate of depression was 9.8/100 patient-years (237 events). Six events of suicide/self- injury occurred, four of which were serious, with one resulting in death. There were seven deaths in the study, and one during the follow-up period with two resulting from pneumonia and one each from cardiac arrest, coronary artery disease, acute respiratory distress syndrome, respiratory failure, retroperitoneal hemorrhage, and suicide.

As the number of participants declined, the percentage of patients who achieved an SRI response increased from 32.8% at year one week 16 to 75.6% at year 12 week 32. The occurrence of flares was highest in the first year and was consistently low throughout the study.  The percentage of patients achieving low disease activity increased throughout the study from 13.9% at year one week 16 to a maximum of 57.1% at year 13 week 32.

FINAL THOUGHTS

This study represents the longest longitudinal examination of SLE patients on belimumab. The authors found that belimumab was safe, well tolerated, and efficacious over the 13 years of follow-up.

Dr. Wallace and colleagues state, “That approximately one-third of patients continued to receive belimumab for at least 10 years is extraordinary, particularly in light of adherence rates to other medications used for and studied in SLE.”

Undertaking extended examinations looking at safety and efficacy are very important for drug trials. Often clinicians don’t get to see the long-term effects of prescribed medications due to patients moving, dying, or simply changing practices.

The authors point out in their conclusions that, “It will be important to investigate the effects of stopping belimumab in patients who have achieved stable, long- term low-level disease activity.” This point is crucial to understanding the long-term effects of belimumab in SLE since evidence in other drugs points to success with tapering or stopping treatment during sustained remissions.

With the strong evidence of long-term success presented in this study clinicians should feel confident in prescribing belimumab for their patients with SLE.

ABOUT THE AUTHOR

Gregory M. Weiss, M.D., is a cardiothoracic anesthesiologist practicing in Virginia. He is a frequent contributor to Rheumatology Network.

REFERENCE

Wallace, D. J., Ginzler, E. M., Merrill, J. T., et al. Safety and efficacy of belimumab plus standard therapy for up to 13 years in patients with systemic lupus erythematosus. Arthritis Rheumatol. 16 February 2019, Accepted Author Manuscript. doi:10.1002/art.40861