Editor’s Note: We’re excited to introduce a new recurring column in the 2017 issues of Spondylitis Plus: “Q&A with a Medical Professional.” The column will feature questions from our readers on various aspects of spondylitis, and answers from experts. We are kicking off this feature with a Q&A with noted rheumatologist and researcher, Lianne S. Gensler, MD. Dr. Gensler is Associate Professor of Medicine, and Director of the Axial Spondyloarthritis Clinic at the University of California, San Francisco.
The next installment of this feature will be focused on questions for physical therapists and will appear in our Summer issue.
Please send in your questions to firstname.lastname@example.org. Please keep your questions general in nature, and keep in mind that physicians will be unable to provide medical advice about your specific case through this format.
If you have already submitted your questions through the online survey emailed earlier this year, rest assured we have them!
Question: We hear so much about customized medicine in the media. We know they can test for whether a mood altering drug, such as Zoloft or Prozac, will be metabolized well or not. These tests can categorize whether they will probably reach the therapeutic dose, or whether it’s likely not to work. Is there any work being done in this regard with biologic medications?
Answer: There are commercially available tests for a couple of the biologics (infliximab and adalimumab) to determine what the level is in the blood and whether a patient has developed antibodies to the drug. This is routinely assessed in inflammatory bowel disease and the gastroenterologists have guidelines of what to do in various situations. They also have a target drug level they aim for. There is less evidence in rheumatology as to what the level should be and what to do in the various scenarios.
Question: I read recently that taking an anti-inflammatory with a TNF inhibitor like Humira can stop the progression of spondylitis. My rheumatologist says they don't stop the progression, that they merely treat symptoms. Which is true?
Answer: The emerging data is that taking a TNF inhibitor like adalimumab (Humira) is associated with a significant reduction in spinal progression. We do not believe it simply treats symptoms, though proving the effects are causal has been challenging. (References: Haroon et al Arth Rheum 2013 and Gensler LS et al ACR supplement 2016)
Question: What are the latest risks of lymphoma or other cancers from biologics (from FDA testing through aftermarket reporting?) People are still scared by the warnings on the packages, but I hear that the incidences are really much lower since we have many more users now.
Answer: There has never been a study in spondyloarthritis to show an increased risk of any kind of solid cancer or blood cancer in patients using TNF inhibitors. The original study showing this association has not been reproduced. Many people believe that these data (performed in rheumatoid arthritis) were biased in that those patients were more severe from longstanding untreated disease and therefore at higher risk for lymphoma to begin with. In fact there may be emerging data in cancer research that TNF itself may drive cancer, so this may shift the entire paradigm of how we look at the risk in patients with rheumatic diseases. I generally think the risk of cancer in spondyloarthritis is far outweighed by the benefits of TNF inhibitors in those with active arthritis. There may be a slight increase in non-melanoma skin cancers, but these are generally not dangerous and can usually be removed if they arise. If they occur, there are often other risk factors like UV exposure and fair skin, so UV protection should be considered.
Question: What is the long term effect of methotrexate on my body? What should I be concerned about? Also, I usually need one to two prednisone taper treatments a year if I flare up. What are the long term effects on my body with prednisone use?
Answer: Methotrexate is one of our oldest rheumatology medications and is usually well-tolerated long term. It can affect the liver, and liver function should be measured every three months. It is metabolized in the kidney and if the kidneys do not work well, then methotrexate may not be a good option. This is especially true because as it builds up in the system it can suppress the bone marrow from producing cells (like a chemotherapy) and this can be dangerous. None of these are usually issues with regular blood monitoring. It does suppress the immune system and is associated with infections, but this is especially true if combined with biologics and prednisone. It does not need to be stopped during joint surgeries like knee and hip replacement.
Prednisone long term can have more significant side effects including infection, bone loss leading to osteoporosis and fracture. Fracture is a serious complication because AS patients are at risk for fracture and adding prednisone to that risk likely escalates it further. Prednisone causes weight gain which is bad for AS, but stopping prednisone does not help weight loss. With more chronic use, patients can get thinning of the skin and the adrenal glands can shut down because the body is being supplied by an exogenous source of steroids (with the prednisone). This makes it difficult to taper prednisone quickly, leading to more side effects. Other complications include steroid induced hyperglycemia (diabetes), lipid problems, fluid retention, glaucoma, and muscle weakness called myopathy. In general, the guidelines recommend against the use of oral or injectable prednisone for AS because the doses needed are high and the side effect profile often outweighs the benefit.
Question: Is there any way to prevent recurrences of uveitis for a patient with AS?
Answer: Some patients will not have recurrences of uveitis, however some will and sometimes frequently. In patients with frequently recurrent uveitis and active AS warranting a biologic, using certain biologics (the TNF inhibitors characterized as monoclonal antibodies - adalimumab, certolizumab, golimumab and infliximab) will reduce the recurrence rate of uveitis. The only TNF inhibitor that is not as good for uveitis is etanercept, but older data suggests that even this biologic is associated with less recurrence.
Question: I have dormant TB. What medication can I take? Any biologics?
Answer: Dormant tuberculosis (TB), otherwise known as latent TB, should not preclude treatment for axial spondyloarthritis /ankylosing spondylitis. However, if the TB test is positive by the blood test or the skin test (one of which is required to be performed in all patients before starting biologics) then TB antibiotics should be administered for at least two weeks before starting the biologic and continued for up to nine months (depending on medication used). This is most relevant with TNF inhibitors (where the risk for reactivation is the highest).
Question: I have taken various biologic drugs over the years, but each one keeps losing effectiveness after a couple of years and so I have to keep switching. Can you explain why this keeps happening? Will I likely ever find a biologic that works for many years?
Answer: There are many reasons why patients lose response to biologics. If, when the biologic is first used, the response is very positive and then this decreases, it could be that the patient has developed an antibody against the drug, causing it to be cleared more quickly and therefore decreasing its effectiveness. In this setting, adding a low dose of a medication like methotrexate may help prevent this from happening. Not all of the biologics are prone to this happening. Infliximab is most strongly associated with this phenomenon but it rarely happens in etanercept. It may also be that patients stop responding as well because the disease becomes more active or progresses and the damage is what is causing the pain. The patient’s rheumatologist should evaluate the patient to determine the most likely cause of the reduction in response. I believe we will keep developing more effective drugs with fewer side effects; I therefore believe you will find a medication that works for you for long-term.
Question: Can advanced ankylosing spondylitis affect the heart? If so how?
Answer: Long standing AS is associated with inflammation and inflammation is not good for the heart. The most common heart effects in AS are coronary artery disease and atherosclerosis. This may be associated with an increased risk of heart attack and/or stroke. The older literature suggested AS patients also developed inflammation and leakiness of the aortic valve. In more recent studies, when compared to an age matched healthy population, this association has not been detected. It may be that by treating inflammation with the newer medications like the biologics, we are preventing some of the cardiovascular complications.
Question: Is there a surgical procedure to correct kyphosis?
Answer: There is a surgical procedure called a spinal osteotomy. This is a relatively high risk surgery and should only be performed with severe kyphosis where the patient’s horizontal gaze may be compromised, and only at specialized centers that have significant experience with this procedure.
Question: I have AS and osteoporosis. Will bisphosphonates cause a worsening of bony exostoses? My hand joints are already extremely distorted by the bony growths. Will a bisphosphonate make them worse?
Answer: Bisphosphonates turn off bone loss from osteoporosis, but they do not turn on bone growth. They should not cause extra bone growth or ankylosis.
Question: Does the benefit of long term use of a bisphosphonate outweigh the risk of osteonecrosis for a 40 year old patient with osteopenia?
Answer: I would rarely treat a 40 year old with bisphosphonates in the setting of AS because the usual cause is inflammation and stiffness and these can be treated with AS medications like TNF inhibitors. In addition the reason to treat is really because of the risk of osteoporosis and fracture. Since younger patients (40 is young) are at lower risk for fall, they are also lower risk for this outcome. When AS patients are treated with TNFi, bone density increases as inflammation is suppressed. There are occasional times when we do use bisphosphonates in younger patients. The risk of jaw osteonecrosis from oral bisphosphonates in patients without a history of radiation to the head/neck and with good dentition is quite rare, so when truly indicated, the benefit to bone health outweighs the risk of osteonecrosis. We do not like to use bisphosphonate for too many years without a break.
Question: What is the current status of ustekinumab (Stelara) for the treatment of ankylosing spondylitis? My rheumatologist has recommended it to me. I had disastrous reactions to both Enbrel and Humira.
Answer: A small proof of concept study suggested that ustekinumab may be helpful in AS. Phase three trials are underway both in patients that have never used biologics, and in those that did not respond or did not respond well to TNF inhibitors. Results are not yet available. Ustekinumab was recently FDA approved for Crohn’s disease and is approved for psoriasis and psoriatic arthritis.
Question: What treatment do you recommend for enthesitis pain? Enbrel and NSAIDs don't help me with this ongoing issue in many of my joints (I'm female and HLA-B27 negative); topical NSAIDs help only temporarily.
Answer: NSAIDs and biologics are the only medications expected to work. If there is no relief from these agents, then making sure this is enthesitis causing the pain would be important. Entheseal pain does not necessarily come from inflammation and the above mentioned medications only work by suppressing inflammation.
Question: How many patients with AS also suffer from Crohn's disease? What about the percentage of Crohn's patients who develop AS? Is there any difference in these populations based on gender?
Answer: About 20% of patients with inflammatory bowel diseases (IBD), of which Crohn’s is one, develop AS or some amount of sacroiliitis. About 8% of AS patients have IBD, but the majority of AS patients without any gastrointestinal symptoms have some amount of microscopic inflammation in the gut supporting the strong relationship between these two conditions. There is no data to suggest a gender difference in the setting of IBD and AS.
Question: Does a difficult or stressful childbirth contribute to triggering the onset of spondylitis symptoms in the child? Any research on this?
Answer: There is no data to suggest that a baby born under stressful conditions is more at risk for spondyloarthritis. We do know that the vaginal microbiome is important for babies as they are delivered. Babies born via cesarean section will miss this exposure.
Dr. Gensler is the Director of the Ankylosing Spondylitis Clinic at University of California San Francisco (UCSF). She is an Assistant Professor of Medicine in the division of Rheumatology and sees patients in addition to teaching and performing research in spondyloarthritis.
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