Rituxan Risks

Is Rituximab really as dangerous as it appears?
The PDSA article on B-cell depletion states the following:

In a review of published studies about 3% of ITP patients treated with rituximab had become extremely ill or died.⁶

Reading the abstract of the cited article reveals something worse: 2.9% of the adult ITP patients died. Nine of 306.

If this is accurate, then Rituxan is being seriously over-prescribed. The common platelet count cutoff of 50k seems seriously high, considering there is very little risk of death [from bleeding] until much lower counts are reached.

Am I missing something?

Rob, I think that the deaths are usually in patients who have a number of serious illnesses as well as ITP, that's been my understanding.
Erica

I agree with Erica. Also, you have to figure in ITP patients who are asplenic and/or on other immunosuppressants. The risk is obviously higher for that group due to infection. It has been published many times that more people die of infection than they do from bleeding.

However, I do agree that Rituxan has been over-prescribed in certain cases. I've seen 8 infusions given in some instances and I've seen maintenance doses given. I truly do not see the necessity of that at all.

Thanks, Erica and Sandi.
The Rituxan information www.rituxan.com/ra/hcp/safety/important-safety-information/index.html for rheumatoid arthritis patients is also somewhat reassuring (ITP info is scarce, since Rituxan is not approved for ITP), but I would love to see in print an actual number of how many deaths were not attributable to preexisting conditions.

Ellen is back down into the 50s, and Rituxan would be her next course of action. Would waiting until counts fall below 20k (assuming no serious symptoms) be a reasonable strategy to balance the risks? Maybe fifteen? ten?

If I felt well at low counts, and no serious symptoms, I'd treat under 30k. I feel too scared at lower counts. It's a judgment call, of course.
Erica

Rob - it's a tough call. Since Rituxan can take time to work, you'd want to begin before counts get too low. But you also wouldn't want to treat if counts are decent based on the thought that they 'might drop'. You just have to do what feels right based on the situation.

It would be helpful to have better stats on Rituxan deaths. There was a woman here long ago who had ITP and died of sepsis. She was asplenic, on low dose Prednisone and using Rituxan. She got sick and died within 24 hours. She is the only one that I know of, but I'm sure there are more (probably not a lot).

Patients just have to be aware of the risks and take precautions. Rituxan by itself probably isn't too risky, but adding other factors in can change that risk.

Other than an internal hemorrhage, what else would cause death from ITP? I just read a 26yr old female with ITP that passed away. One day she was fine and 4 days later she was on life support. I wonder if there were other undetected health issues that may have contributed to her death? I am not sure what I want to do if this transfusion fails.

Dean:

It's hard to say what caused her death since we don't know the story. Bleeding is the only way to die directly from ITP, but there are obviously other indirect reasons that one could die while having ITP. I'd think the most common would be treatment-related, such as blood clots or infection. Both of those could cause a person to be on life support.

If your transfusion does not work (and again, it probably won't), you'll need to make a decision. Rituxan worked well for you before, right? You could try that again....maybe low dose this time instead of the full dose? There are quite a few options. You'll figure it out and you'll be okay. We're here to help you think it through.

The first study that I find when I google rituximab and mortality states:

There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections.

Of the 370 patients, there have been 11 deaths (3.0%
of patients) reported following treatment with rituximab
(Table 2). Patients with ANCA-associated granulomatous
vasculitis were the group most affected (four
deaths), followed by those with polydermatomyositis
(three deaths). Infection was the major cause of death,
which was the cause in seven cases. The timing of the
11 deaths after rituximab therapy (mean 11.6 months)
ranged between 0.8 and 31.3 months after the first infusion
of rituximab. Notably, the study protocol required
documentation within six months after the last rituximab
therapy. Thus, five deaths occurred in this period;
for the remaining six deaths, these occurred outside the
protocol-specified period of six months and, therefore,
the data of this patient group are less certain. Patients
(n = 7) with a short interval between rituximab infusion
and death (< 7 months) had highly active, uncontrolled
disease and received rituximab as a final option during
intensive care therapy. Four of the deaths occurred
more than 11 months after rituximab therapy. Two
patients with ANCA-associated granulomatous vasculitis
died 13.8 and 11.1 months after the last infusion of
rituximab (31.3 and 12.7 months, respectively, after the
first infusion) and two patients with polydermatomyositis
died at 12.7 and 14.2 months following first and only infusion. Notably, within the largest patient groups of SLE and MS, no deaths were reported.

I should add that the post above doesn't mean that I think someone with a count of 50K should treat in the absence of symptoms. I've been at 40K for about 6 months (maybe more), and I am not treating.

However, I'm debating a low dose of rituxan before my deductible clock starts over in January, because up until this year I was hovering around 100K for several years. My doc is amenable to whatever I decide, though she doesn't usually treat with counts above 30K.