Commentary
Video
In an interview with Pharmacy Times®, Richard Furie, MD, chief of the division of rheumatology at Northwell Health, explains how pharmacists play a critical role in educating and mitigating the risk of infections in patients with lupus nephritis being treated with obinutuzumab (Gazyva, Gazyvaro; Genentech). Furie highlights obinutuzumab as part of a growing pipeline of lupus nephritis treatments but notes that questions remain among clinicians regarding its optimal use alongside standard treatments like belimumab (Benlysta; GlaxoSmithKline) or voclosporin (Lupkynis; Aurinia Pharmaceuticals).
Pharmacy Times: What are the anticipated challenges and considerations in integrating within standard lupus nephritis treatment regiments, and how can pharmacists collaborate with the patient's care team to address these potential concerns?
1. Obinutuzumab is effective but lacks clear preference over existing lupus nephritis treatments, requiring time for clinicians to establish best-use cases.
2. Ensuring patient vaccination is critical for infection risk reduction in immunosuppressed lupus patients.
3. Matching patients with the most suitable biologic therapy is the next step in optimizing lupus nephritis outcomes.
Richard Furie, MD: We've made progress. As I mentioned, the development of drugs for lupus has been really challenging. We've kind of switched from cyclophosphamide—intravenous cyclophosphamide—which was pioneered by the NIH years ago to mostly using mycophenolate. Then we had successes with belimumab and with voclosporin. I think most of us, but probably not all, favor using 2 drugs: that is mycophenolate and belimumab, or mycophenolate and voclosporin, as opposed to mycophenolate alone. And the study showed that there was an incremental benefit. Now we have obinutuzimab. So, the question is, and I'm not sure anybody has a great answer just yet, is one preferred over the other? Individual clinicians may have a preference. For example, a nephrologist may be more comfortable with voclosporin, a rheumatologist more comfortable with belimumab—a rheumatologist certainly more comfortable with rituximab (Rituxan; Genentech), and therefore they should be comfortable giving obinutuzimab much like rituximab. But the temptation is to compare study results, and I preach: do not compare study results. You can compare study designs, but the studies are different; different enrollments, different end points, and the end points occur at different times. No one can resist that temptation of lining up a table and looking at complete response rates in the studies. I think it will take a little bit of time for everybody to get comfortable with their drug of choice. There's no question that obinutuzimab is an effective drug, and the safety profile, short of the COVID experience, looked pretty good. That just brings up another point: patients must be vaccinated. Not just to COVID, but influenza every year, pneumococcus per the guidelines, shingles with Shingrix (Zoster Vaccine Recombinant, Adjuvanted; GlaxoSmithKline). I'm not really sure what to do about RSV, but vaccines are so important.
Pharmacy Times: What do we know about the long-term durability of response with obinutuzumab, and how can pharmacists support adherence to therapy to optimize patient outcomes?
Furie: Well, I must say, we have limited data on the long term. It really depends on how you define long-term. Let's go back to the phase 2 NOBILITY trial. That study was a 2-year study, so we have 2 years’ worth of data, and because this study was 2 years, we're actually able to do some analyses that couldn't really be done with a 1-year study. One of the key analyses was to look at GFR slope over time, and that's the name of the game in treating patients with kidney disease. You're born with a certain number of nephrons, and from birth till death, you lose some each day. That's without having lupus. But throw in a kidney disease on top of that, and you'll have accelerated loss of nephrons, which translates into loss of GFR over time. So, the natural progression of GFR is to decrease over time, and then if you have a kidney insult, that accelerates the GFR loss. We looked at GFR slope over the course of the NOBILITY trial and saw a significant benefit if you received obinutuzimab compared with standard of care. That analysis was also done in the REGENCY study; it did not reach statistical significance, but there was numerical superiority. Those are sort of the long-term data from the study; I don't know if that's long-term enough, but if you extrapolate that GFR benefit in 2 years, it will hopefully be amplified over the lifetime. We happen to use obinutuzimab, since it has been approved since 2013 or so, and we're compiling our data because we've had patients on it for about 9 years now. So, I'll let you know after we finish our analysis.
Pharmacy Times: Is there anything else you would like to add?
Furie: Well, as I've mentioned before, we've struggled with our lupus trials; no question about that. It's so exciting to see positive data, and we now have choices. We were yearning for a drug, and now we have several drugs for Lupus nephritis. I think we have to learn how to use these drugs and try to match up the appropriate patient with the appropriate drug. We're basically talking about precision medicine, and that's the next frontier. But the bottom line is, the benefits to our patients have been enormous. If you go back to, well, I mentioned 1948, so what happened in 1948? That was the discovery of compound E, or cortisone, and that was transformative for all our inflammatory diseases; no question about that. The life span of someone with lupus was not good back then; in fact, 7-year survival pre-steroid era was 50%. Each era that a new class of drug was introduced, for example, immunosuppressors, cytotoxins, and biologics, we see increased survival. We are, unfortunately, still losing patients to lupus, so about 15% of our patients die within 15 years of diagnosis. We need to reduce that to zero—not only a reduced mortality rate, but reduced morbidity. It's all through clinical research like this that will achieve that.
