I’ve been on seven – count them – seven different biologic medicines since being diagnosed with rheumatoid arthritis. I started with several anti-TNF biologics and then moved to several others even bouncing back to try another anti-TNF before eventually trying Rituxan. I’ve self-injected with auto-inject pens, self-injected with needles, and seems like I’ve had every type of infusion possible. This is probably something of a record although similar stories emerge on discussion boards from time to time. With some of the biologics, I would respond for a period of time and then it would stop working. With others, there was never a response. With yet others, there would be some adverse side-effect causing cessation. This is not all to unusual as it is widely know in the rheumatology community that upwards of 30% of RA patients do not positively respond to anti-TNF biologic medicines.
Posts Tagged ‘enbrel’
Posted in Uncategorized, tagged B Cell lymphocytes, CD20, enbrel, fatigue, humira, rheumatoid arthritis, Rituxan, Rituximab, stiffness, swelling, tendon tear, TNF inhibitor on December 10, 2013| 7 Comments »
I had a follow-up appointment with my rheumatologist to see how the Rituxan/Methotrexate combination is working. Since the time I started Rituxan, an MRI of my right elbow revealed a 50% tear in a tendon and active inflammation in the joint space. A cortisone shot from the orthopedic surgeon seems to have calmed things down for the time being. My right ankle displays regular sharp pain feeling much like it did a couple of years ago when I had surgery to remove bone erosion and repair soft tissue damage. Under examination from the rheumatologist, my toes were tender and painful – something I never noticed since I don’t regularly inspect my toes. I still experience considerable overall stiffness, joint pain, and fatigue. But the good news was that my rheumatologist noticed that I had less tenderness and swelling in my finger joints (it amazes me how she distinctly remembers such things). I agreed as I had noticed the same thing. My wife, one of the best and objective observers, also noticed some improvement over the past few weeks.
When I started other biological treatments, it was pretty clear whether or not it was working within the first few weeks. But that is not the case with Rixutan. Unlike anti-TNF drugs like Enbrel and Humira that can work more quickly, the full effect of Rituximab may not be seen for 16-24 weeks (National Rheumatoid Arthritis Society). My first Rituxan infusion was on September 23rd and I’m sitting at about 11 weeks since I started. According to the Rituxan frequently asked questions (FAQ) website,
“At the time of their first checkup—8 weeks after starting treatment—many of those people had seen an improvement in their symptoms. And 6 months later, many were still experiencing improvement.”
The hope remains that this combination will continue to cause an improvement in symptoms. My rheumatologist believes that with the RA out of control for so long, it may take some time for a treatment to catch up and put out the inflammatory fire.
In this fast-paced, electronic society, we demand everything instantly. It’s difficult to wait for a treatment to take effect. But with the complex biological processes involved with rheumatoid arthritis, the immune system, and Rituxan, we must be patient. While scientists aren’t completely sure about the exact details, it is believed that Rituxan works by depleting the production of B cell lymphocytes by targeting an antigen called CD20 (see graphic) (Pescovitz, 2006). Since B cell production takes time and Rituxan only works on a portion of the production line (see graphic below from the Rituxan website), it stands to reason that it will take time for the therapeutic action to take hold. Slow and steady, hold the course, wait and see…these are all operative words at this time.
Posted in Uncategorized, tagged AbbVie, Actemra, American College of Rheumatology, Amgen, Biotechnology and Pharmaceuticals, Bristol-Myers Squibb, Cimzia, clinical trial, enbrel, Genentech, humira, Jansenn, medicine, Orencia, Pfizer, Pharmaceutical industry, remicade, rheumatoid arthritis, Rheumatoid Patient Foundation, Rituxan, Roche, Simponi, Xeljanz on November 6, 2013| 5 Comments »
I recently had the privilege to attend the annual meeting of the American College of Rheumatology. Considerable time was spent in the exhibit hall since, in addition to presenting a research paper, I was also volunteering at the booth of the Rheumatoid Patient Foundation.
The exhibit hall was overwhelming and the cavernous room was dominated by pharmaceutical companies. There were dozens of exhibits from large to small companies including, but not limited to, the following who provide many of the major biological treatments for RA:
- Jansenn (maker of Remicade and Simponi and a subsidiary of Johnson & Johnson)
- AbbVie (maker of Humira)
- Genentech/Roche (maker of Actemra and Rituxan)
- Amgen (maker of Enbrel)
- Bristol-Myers Squibb (maker of Orencia)
- Pfzier (maker of Xeljanz)
- UCB (maker of Cimzia)
These pharmaceutical companies commanded the majority of the space and had professionally designed exhibits replete with multimedia presentations, large colorful signs and displays hanging from the ceiling, leather lounge chairs, espresso bars, snacks, colorful print materials, conference rooms, and an army of 20-30 sales representatives each. The rumor floating around was that these traveling exhibits cost upwards of $100,000 each in addition to the staff and other associated costs. They replace them every year. It is evident that the big pharmaceutical companies, especially those with expensive biological drugs on the market for RA, have vast amounts of funds to spend on sales and these exhibits. Based on this level of spending, it is obvious that this is big business and it is important for these companies to interact with the doctors and other health care providers who attend this conference in an effort to increase the sales of their drugs.
I enjoyed free espressos from Genentech/Roche each day – the manufacturer of my current RA medication Rituxan. One day while drinking my coffee and looking over research materials on Rituxan, a sales representative approached me obviously expecting me to be a doctor. I told her that I was a patient advocate who was actually taking Rituxan. She literally took a step backwards and told me that she was sorry and hoped I felt better. I laughed and said thanks and grabbed some print materials on clinical trail results and side effects. This awkward moment drove home the potential disconnect between the company sales force and patients. In spite of this brief and awkward interaction, the pharmaceutical companies must be commended for several things.
Most of the research and development (R&D) behind these biological treatments for RA were paid for by the pharmaceutical companies. Oftentimes, the basic research, paid for by government or private foundation money, starts with a university-based researcher. These basic ideas lead to potential new treatments and the drug companies take over the onerous and lengthy task of developing and trying out new drugs. For biological drugs, this process may take years. And for every drug that makes it to market, there may be dozens that fail. Such development processes are extremely expensive and those costs are passed onto the patient in the cost of the drug. During the conference I was able to speak with several companies about RA treatments that are in Phase III Clinical trails (the last phase before seeking government approval). The concern is about who is going to pay for the R&D once pharmaceutical companies go over the so-called patent cliff in the next few years when their patents run out and they start to loose market share and profits.
Another patient benefit provided by the pharmaceutical companies for expensive biological treatments for RA are co-pay assistance plans. All of the companies listed above have such plans and they pay out millions of dollars each year helping patients be able afford treatments that can cost between $16,000 – $40,000 a year. This assistance, while extremely beneficial to those who need it, also demonstrates the large profit margins built into the “retail” costs of the drugs.
During the conference, I also met several consultants who are contracted by pharmaceutical companies to conduct research related to patient reactions and opinions about their products. While one may cynically infer that the companies are simply trying to increase their market share by pressuring the patients to ask for their drug, it was clear from the consultants that they genuinely want to increase the positive interactions between patients and the pharmaceutical companies in an effort to improve patient care and future drug development.
Yes, pharmaceutical companies are huge for-profit entities with a major goal of making money for shareholders. And the companies with major biological treatments for RA make enormous profits (Humira sales alone for the 4th quarter of 2012 were $2.7 billion). But they also bear the brunt of the R&D process, help with co-pays, and appear to seek patient interaction. As the patent cliff approaches, time will tell how it will impact these companies and the future of RA drug development.
Posted in Uncategorized, tagged Arava, Azathioprine, bacteria, CDC, Centers for Disease Control, Cimzia, corticosteroids, enbrel, humira, immune system, immunocompromised, immunosuppressed, infection, methotrexate, Orencia, RA, remicade, Rituxan, Simponi, vaccine, virus on August 30, 2013| 6 Comments »
Ever since the H1N1 swine flu scare a few years ago, I make it a point to get a flu vaccine every autumn. When receiving a regular physical exam from my general practitioner last week, the doctor suggested that a pneumococcal polysaccharide vaccine be added…
To check out the rest of this post, go to the newly launched website rheumatoidarthritis.net. I will be writing posts for this site periodically as a Patient Advocate and will continue to make regular posts at this personal blog.
Posted in Uncategorized, tagged Ablynx, Actemra, autoimmune, biologicals, Bristol-Myers Squibb, Cimzia, enbrel, humira, Interleukin-6, Orencia, research, rheumatoid arthritis, tnf, TNF blocker, Tocilizumab, Tumor necrosis factor-alpha on August 23, 2013| 5 Comments »
With the research net being cast widely and deeply by researchers and pharmaceutical companies, it’s clear that the currently approved treatments for rheumatoid arthritis are not having the intended impact on all patients (see this recent post on lack of remission). Unlike some infectious diseases where there is a treatment that often results in a cure (e.g. tuberculosis) or eradication via a vaccine (e.g. polio), no such remedy currently exists for RA. Last year I wrote a post about the large variety of biological treatments for RA that are currently in the development and testing pipeline. And this did not even include the myriad of small molecule drugs being developed to target the so-called JAK-STAT pathways of which Xeljanz (tofacitinib) is the only one currently approved in the United States but not approved in Europe.
The vast majority of approved RA biological treatments focus on inhibiting the tumor necrosis factor (TNF) alpha molecule which is overactive in autoimmune patients. The TNF blockers Enbrel, Remicade, and Humira account for the majority of biological prescriptions and control a vast portion of the market. The newer TNF blockers Simponi and Cimzia have recently joined the fray. Other parts of the involved biological pathways have been targeted for treatment including costimulatory protein CD-40 (Rituxan), interleukin 6 or IL-6 (Actemra), and T cell lymphocytes (Orencia).
In spite of the major focus on TNF alpha, a Belgium company called Ablynx now proposes that over the next few years, the “Anti-IL-6 pathway will dominate as the preferred biologic after anti-TNFα treatment.” They predict that 16% of the RA biological market will consist of IL-6 inhibitors by the year 2021. This focusing on IL-6 signaling pathways was proposed in 2008. In addition to Actemra (tocilizumab) which is currently approved in the U.S. and Europe, other antibody treatments targeting IL-6 are being developed including sarilumab by Sanofi and Regeneron, sirukumab by GlaxoSmithKline, and clazakizumab by Bristol Myers Squibb.
Ablynx is currently completing Phase II clinical trials of an IL-6 inhibitor called ALX-0061 and the results show strong treatment efficacy and safety profiles. Instead of being made of large monoclonal antibody (MAB) molecules like most of the current biological medicines, the company Ablynx focuses on producing smaller components called “nanobodies” or fragments of antibodies (FAB) (see this Scientific American article). FABs are cheaper to produce, may produce fewer side effects, and are less prone to breakdown in harsh environments. Ablynx clones the human FABs in llamas before isolating the molecules (see this report).
It is heartening that much research continues on the development and testing of treatments for RA.