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Epratuzumab: Targeting B-Cells To Treat SLE

As research laboratories across the world investigate new lupus treatments, efforts increasingly focus on suppressing B-cell activity.  B-cells are major actors in the normal immune response.  With lupus, the immune response is not normal and neither is the behavior of B-Cells.  During an active disease phase, the immune system attacks organs and wreaks havoc. B-cells play an important role in this process.
Historically, lupus medicines have sought to control the aberrant immune response by tamping down the entire immune system.  Established remedies (for example: glucocorticoids  and cyclophosphamide) are not very specific in suppressing the immune system. Instead of acting on the parts of the system that are especially aggressive, older medicines depress the general immune response. While this approach is often effective in controlling symptoms, it can sometimes have a devastating impact on the overall health of the patient.
An analogy to the traditional approach might be found in the case of a broken light switch. In order to repair the switch, an electrician could shut down all the circuits in a house. This certainly would insure that electricity isn’t flowing to the broken switch–it would also insure that electricity isn’t flowing anywhere else in the house, either. A total shutdown might have far-reaching consequences–melting ice cream, for instance.  However, if the electrician decided to shut off only the circuit associated with the broken switch–that is, if she/he targeted the problem area–disruption in the household would be minimized.
That’s the principle behind targeted B-cell suppression. If only B-cells are affected, the impact on the patient might not be as widespread as it would be if an older generation, immune-suppressant drugs were administered.
The problem with new generation, B-cell-targeting drugs is that, so far, they haven’t proven to be very effective. This is the case with belumimab and rituximab. While both of these drugs are prescribed at present and do help people in certain situations, neither has lived up to its early promise.
Epratuzumab is a B-cell-targeting drug with a difference. This drug doesn’t try to suppress all B-cell activity.  It is designed to address only a specific part of the B-cell: CD-22, which is on the surface of the cell.
It is believed that a major benefit of epratuzumab over other B-cell-targeting drugs may be that it does not depopulate all of the B-cells in the course of treatment. It seems that epratuzumab only eliminates “up to 45% of circulating B-cells“.  Rituximab, on the other hand, eliminates  greater than 90% of circulating B-cells.  Since B-cells are essential for a robust immune response, wiping these cells out increases the risk of infection. Keeping viable B-cells might help to limit that risk.
Epratuzumab has gone through Phases I and Phase II clinical trials. Phase III is currently underway.  A January 2013 article published in the Annals of Rheumatology describes the drug as promising. The journal reports that epratuzumab was well tolerated by study participants, even at high doses (2400 mg. week); also, the journal reports, trial subjects who received the medication experienced better outcomes than the control group that received placebo.
In February 2015 Euroscan (a European evaluating organization) issued a report on the safety of epratuzumab and side effects experienced by study subjects. Side effects were noted to have occurred as follows: 10% experienced conjunctivitis; 45% upper respiratory infections; 28% diarrhea and 28%  headache; 14% experienced migraine and 34% caught a cold; 24% experienced nausea; 24% had bronchitis; dizziness was reported by 10%; 10% ran a fever; sinusitis was reported in 31%; abdominal pain occurred in  31%; 10% had chest pain; 10 % had a cough.
Phase III of the epratuzumab clinical trial has 1400 participants; these patients have moderate to severe SLE. The final report on Phase III will be issued in 2019.  The drug’s manufacturer, UCB and Immunomedics is optimistic, based on the results of  Phase I and Phase II.  UCB reports that study participants who received epratuzumab showed a  “24.9% treatment advantage over placebo”.
Will epratuzumab  be a ‘magic bullet’ for lupus patients? A lot of people certainly hope so. Clinical trials and actual practice will prove whether or not this hope is misplaced.
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