Anifrolumab reduces lupus disease activity across musculoskeletal, mucocutaneous domains
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Anifrolumab improves systemic lupus erythematosus disease activity across musculoskeletal, mucocutaneous and immunological domains, according to a post-hoc analysis of TULIP-1 and TULIP-2 data published in The Lancet Rheumatology.
“Incomplete disease control leads to progressive organ damage, poor quality of life, and increased mortality, with approximately half of all patients with SLE developing organ damage within 10 years of diagnosis,” Eric F. Morand, MBBS, of Monash University, in Melbourne, Australia, and colleagues wrote. “Therefore, the capacity of a medical intervention to improve activity across multiple systems, and thereby potentially prevent organ damage, is a desirable attribute.
“Organ-specific measures of skin and joint responses were assessed as secondary endpoints in TULIP-1 and TULIP-2,” they added. “The similarity in design of the TULIP-1 and TULIP-2 trials facilitated pooling of data for assessment of individual organ systems with greater statistical power than is possible with the individual trials alone.”
To analyze the efficacy of anifrolumab (Saphnelo, AstraZeneca) on organ domain-specific SLE disease activity, Morand and colleagues pooled data from the randomized, placebo-controlled, phase 3 TULIP-1 and TULIP-2 trials. In these trials, adults aged 18 to 70 years with moderate-to-severe SLE — despite treatment with oral glucocorticoids, antimalarials, immunosuppressants or a combination of these — were randomly assigned to receive either 300 mg of intravenous anifrolumab or placebo every 4 weeks for 48 weeks.
For the post-hoc analysis, Morand and colleagues pooled data from 726 participants. In all, 360 were treated with anifrolumab while 366 received placebo. Among the included patients, the most frequently impacted organ domains at baseline were musculoskeletal and mucocutaneous, reported in 89% and 86% of cases, respectively.
The researchers examined changes in British Isles Lupus Assessment Group 2004 (BILAG-2004) and SLE Disease Activity Index 2000 (SLEDAI-2K) organ domain scores, Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score (CLASI-A), swollen and tender joint counts, hematology and serology from baseline to week 52.
According to the researchers, participants who received anifrolumab demonstrated greater improvements, compared with placebo, in the musculoskeletal system — 56% of patients versus 44% with BILAG-2004 and 49% versus 40% with SLEDAI-2K — the mucocutaneous system — 54% versus 38% with BILAG-2004 and 55% versus 39% with SLEDAI-2K — and immunological system — 19% versus 11% with SLEDAI-2K. Less frequently impacted domains showed varied responses.
Among included participants with a CLASI-A of 10 or more at baseline, 46% of patients receiving anifrolumab achieved a reduction of 50% or more in CLASI-A at week 52 compared with 25% for placebo. Among patients with at least six swollen joints, 57% of patients in the anifrolumab group had a 50% or more reduction from baseline to week 52 in swollen joint count, compared with 46% for placebo. However, the difference between groups was not significant for 50% or more reduction in tender joint count.
“In pooled data from the phase 3 TULIP-1 and TULIP-2 trials, compared with placebo, treatment with anifrolumab of patients with moderate-to-severe SLE was associated with improvements at week 52 across organ systems, as measured using BILAG-2004 and SLEDAI-2K domain scores,” Morand and colleagues wrote. “In addition, more patients receiving anifrolumab than those receiving placebo had reductions in skin disease and swollen and tender joint counts despite evidence of lower exposure to glucocorticoids.
“These conclusions must be balanced against the safety of anifrolumab; we have separately reported pooled safety data in which respiratory infections and herpes zoster were reported more frequently in anifrolumab treated patients than in those who received placebo,” they added. “Together, these results provide evidence of the benefit of anifrolumab for reduction of disease activity across multiple organ domains among patients with active SLE.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
In this paper, the authors combined the phase 3 lupus trials used for the FDA approval of anifrolumab (TULIP-1 and TULIP-2), and then looked at specific organ system responses compared with placebo. Designing lupus trials and measuring outcomes have been major problems for researchers. Millions of dollars have been spent on trials that were failures. In this post-hoc analysis of combined trials, the studies failed to be powered for the less common manifestations of SLE.
The most common manifestations were musculoskeletal and mucocutaneous (this is consistent with my practice). These two organ domains showed a significant improvement with anifrolumab. Patients in these groups with a high interferon gene signature (INFGS) had a much better response than those with a low INFGS. Joint swelling responded to anifrolumab, but joint counts did not.
I think we see this in our own practices, as concomitant osteoarthritis and fibromyalgia often confound the determination of what is, and what is not, a tender lupus joint. Other domains, such as renal and neuropsychiatric (NP) lupus, did not show a significant response, but this was thought to be due to the low number of cases in both groups. The protocols specifically excluded patients with severe lupus nephritis and severe NP lupus. A separate trial in lupus nephritis is underway.
The immunological domain had significant results with anifrolumab, and these were improvements in anti-ds DNA antibodies, C3 and C4. Patients treated with anifrolumab were usually on lower corticosteroid doses as the trials progressed, compared with placebo.
This paper did not look at pooled safety data (reported elsewhere) but noted respiratory infections and herpes zoster were higher in the anifrolumab group. The risk for herpes zoster is increased with all of our biologics, as I noted in a previous commentary. As practicing rheumatologists, we are pleased to have another treatment option for our lupus patients and time will tell where it belongs in our armamentarium.
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