Saphnelo for Lupus: One of Two Approved Biologics [JUN 2023]

Saphnelo for Lupus: It improved lupus in all domains tested.

Anifrolumab (Saphnelo) has the lupus community excited a
Pronounced saf-NEH’-low
​

Read about how Saphnelo compares to Benlysta in my other blog post. Each has its pros and cons.

Saphnelo–the 2021 FDA-approved drug to treat lupus (the 2nd biologic for systemic lupus erythematosus). Below is a graph and a photo of one of the study participants.

I’ll never forget the first patient I treated. A 90-year-old woman with severe, very itchy subacute cutaneous lupus that did not respond to any other treatments. After just one infusion the rash completely disappeared. It was life-changing for her.

Anifrolumab (Saphnelo) has impressive results. Many patients with cutaneous (skin) lupus had total to near total clearing of their skin inflammation as shown in this pic and like in my 1st treated patient … NOTE… this picture comes directly from the following research study found on the internet. The photo is owned by the ACR’s Arthritis and Rheumatology journal: Furie R, Khamashta M, Merrill JT, Werth VP, et al; CD1013 Study Investigators. Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis Rheumatol. 2017 Feb;69(2):376-386. doi: 10.1002/art.39962. PMID: 28130918; PMCID: PMC5299497.

Research results “in a nut shell” in easy-to-understand language:

The clinical trials for anifrolumab were called the TULIP trials
TULIP comes from the full research study name: ​Treatment of Uncontrolled Lupus via the Interferon Pathway

How does it work?

• Most (70%) of systemic lupus erythematosus (SLE) patients have high levels of interferons
• Interferons cause inflammation in organs, leading to permanent organ damage
• Anifrolumab competes with interferon by attaching to the attachments (receptors) on immune system cells
• Normally, when interferons bind to those receptors, the immune system cells become more active. Then they alert more immune system cells to become more active and attack body organs
• Anifrolumab decreases this cascade of events from happening
• This leads to less inflammation
• It is a biologic monoclonal antibody, so it is expensive

Anifrolumab (Saphnelo) works differently than any drug used in the past to treat lupus!
1st in its class! It is the next FDA-approved drug for lupus. 

​Saphnelo, an FDA-approved drug to treat lupus: How is it given?

Saphnelo is given intravenously (IV), 300 mg, every 4 weeks

Premeds, like Benadryl and steroids, are not required since severe infusion reactions are rare

What were the research results?
There was a 90% reduction of interferons at 6 months in the patients who started off with high levels
Other labs measuring lupus inflammation improved (anti-dsDNA, C3, C4, CH50)
Low white blood cell counts improved and low platelet counts improved

What other good things does Saphnelo for Lupus?

They had less disease activity
Even patients who started without high interferon levels overall improved
In TULIP-2: 57% (46 placebo vs 72 anifrolumab patients) more patients who started with high interferon levels met the primary endpoint with anifrolumab
… 58% more patients! Impressive!
When looking at all patients, a 51% higher number of patients responded to anifrolumab, including those with normal interferon levels!
You do not have to have high interferon levels to respond!
Close to twice as many patients were able to decrease their steroids to goal (25 placebo vs 45 on anifrolumab)
Lower steroids is important because higher doses of steroids cause organ damage
Anifrolumab reduced lupus flares

It especially worked well for cutaneous lupus

Look at the picture above from one of the studies
This patient had an amazing improvement. Many others did just as well
They measured skin activity with a CLASI score and looked for more than a 50% improvement
CLASI stands for Cutaneous Lupus Erythematosus Disease Area and Severity Index

Twice as many anifrolumab patients responded

-The numbers were 25% of the placebo cutaneous lupus patients responded, while 49% on anifrolumab did

How fast does it work?

Reduced disease activity was seen as early as 2 months. My patient above had this dramatic response just two weeks after her infusion.

Potential side effects of anifrolumab

When comparing side effects, it is important to know that the placebo patients were not truly “placebo”
They were receiving other lupus therapies (hydroxychloroquine, steroids, and immunosuppressants)
Most were on immunosuppressants and steroids that cause side effects themselves
The patients on anifrolumab were also on immunosuppressants and steroids
Therefore sorting out what anifrolumab may do vs the other drugs is very difficult

Here are the numbers (combination of three different anifrolumab research studies):

Around 87% of anifrolumab patients and 80% of placebo patients had side effects
This include nuisance, mild side effects
The most common were viral upper respiratory tract (URI) and throat infections (cold-like infections)
Infusion reactions were the other most common (but severe reactions were rare)
For example, 10% of the placebo (standard of care) patients had URIs, 18% on anifrolumab did
This is not surprising, interferon is important for fighting viral infections
Shingles occurred in around 6% of anifrolumab patients and 1%-2% of placebo patients
Again, not surprising since shingles is due to chicken pox virus
(MAKE SURE TO GET A SHINGLES VACCINE, SUCH AS SHINGRIX, BEFORE TREATMENT!)
6% of anifrolumab patients stopped treatment due to side effects; 3% of placebo patients stopped

What patients were not studied?

Patients with severe kidney inflammation (lupus nephritis, LN), brain, and nerve lupus (neuropsychiatric) were not
Therefore, we do not know if it works for them
However, I will go out on a limb and predict it will help LN patients (a lupus nephritis trial is being conducted with anifrolumab)
We know that interferon plays a role in LN
Just because we do not have study results for severe LN patients, this does not mean it does not work

Bottom lines- Saphnelo for Lupus:

– Impressive results, especially for skin lupus
– Low rate of side effects (colds, sore throats, infusion reactions, shingles are the most important)
– Get your Shingrix shot before treatment

As of August 2, 2021, anifrolumab became the next FDA-approved drug for lupus!

Author

Don Thomas, MD, author of “The Lupus Encyclopedia” and “The Lupus Secrets”

Disclosures: Dr. Thomas is on the Speaker’s Bureaus and has received advisory payments from AstraZeneca, GlaxoSmithKline, and Aurinia

References: ​

Furie R, Khamashta M, Merrill JT, et al.; for the CD1013 Study Investigators. Anifrolumab, an anti-interferon-alpha receptor monoclonal antibody,in moderate-to-severe systemic lupus erythematosus.Arthritis Rheumatol. 2017;69(2):376–86.Furie R, Morand EF, Bruce IN, Manzi S, Kalunian K, Vital EM, et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol. 2019;1(4):e208–19.

Morand EF, Furie R, Tanaka Y, Bruce IN, Askanase AD, Richez C, et al.; TULIP-2 Trial Investigators. Trial of anifrolumab in active systemic lupus erythematosus. N Engl J Med. 2020;382(3): 211–21.

Tanaka Y, Takeuchi T, Okada M, Ishii T, Nakajima H, Kawai S, et al. Safety and tolerability of anifrolumab, a monoclonal antibody targeting type I interferon receptor, in Japanese patients with systemic lupus erythematosus: a multicenter, phase 2, open label study. Mod Rheumatol. 2020;30(1):101–8.

Tanaka Y, Tummala R. Anifrolumab, a monoclonal antibody to the type I interferon receptor subunit 1, for the treatment of systemic lupus erythematosus: an overview from clinical trials. Mod Rheumatol. 2021 Jan;31(1):1-12. doi: 10.1080/14397595.2020.1812201. Epub 2020 Sep 17. PMID: 32814461.