Ask the Experts
What are the time limits for different biologics?
We generally recommend maintaining HBV phylaxis indefinitely for patients on biologics and for 6-9 months for those discontinuing biologics.
How do you treat a patient of RA and Fibrosing Alvelitis?
A and fibrosing alveolitis is a particularly challenging situation. Nonbiologic DMARDS (eg, methotrexate or leflunomide) are both suboptimal in this situation. Recent data on TNF inhibitors also suggests there is an adverse safety signal with these agents. Based upon only on theoretic grounds, I would be interested in a trial of rituximab, but know of no data to support its use.
What is the first choice of biologics according to efficacy & safety?
Based upon the available data, there is nearly 100% agreement that the TNF inhibitors represent first-line therapy in a patient with RA. A TNF inhibitor is generally used in combination with methotrexate.
In a patient with refractory RA (not responding to Anti -TNF alfa&DMARDs) Which is better to switch to Abatacept or Rituximab?
There is no consensus about whether to switch to abatacept or rituximab following treatment with DMARDs or TNF inhibitors. One caution to consider is the risk of PML associated with rituximab use. PML has been reported rarely after rituximab, in both cancer patients and patients with RA .
Is it safe to prescribe interferon without treating Rheumatoid arthritis?
Interferon can both induce and exacerbate rheumatoid arthritis (RA). Interferon must be given with caution when a patient with RA needs IFN for conditions such as hepatitis B or C.
What is it's pathophisiology?
This is a complex question but basically it is an immunologically driven illness that occurs in genetically susceptible hosts. It involves T cells, B cells, fibroblasts, macrophages and osteoslasts. Unfortunately the antigenic stimulus is presently unknown.
What are some therapeutic activities for women with RA to improve function in activities of daily living? Activities that will help improve the simple occupational tasks like dressing , etc?
Does the use of adaptive equipment improve activities of daily living in women over 50 with RA?
In addition to effective therapy with a remitive agent (either non biologic or biologic agent) aggressive physical and occupational therapy is essential.
I am a 34-year-old woman from Caracas, Venezuela. I have rheumatoid arthritis and I want to know if rheumatoid arthritis could be caused by the big infection I had the last couple of months. Thank you.
There is no evidence that RA is caused by an infection.
I have a 62-year-old woman with sero-positive erosive RA, MTX induced ILD and pul. HTN, active synovitis with elevated ESR and CRP, ground glass changes on HRCT chest. Has been on 30 mg/day prednisone for over 5 years. What theraputic intervention would you recommend?
The presence of IPF at baseline makes the choice of therapy difficult. MTX-based therapies are to be avoided for obvious reasons. With regards to TNFi, data from the British Society Rheumatology Biologics Registry (BSRBR) is informative. A complete review of the BSRBR database revealed that treatment with any TNFi in patients with preexisting pulmonary disease (n=184) had a mortality rate of 90 per 1000 person-years of follow-up compared to 14 per 1000 person-years of follow-up in those without pulmonary disease (n=6061), which translates into a 6.4-fold higher mortality rate among patients in the former group. After adjustment for age and sex, patients with baseline pulmonary disease treated with biologics had a 4.4 times higher mortality rate (95% CI 1.8-10.7) than patients without pulmonary disease treated with biologic agents. Thus TNFi would not be my first choice. Leflunomide appears safe even in people with underlying pulmonary disease when used cautiously. We have little data on abatacept or rituximab though abatacept has been somewhat problematic in patients with underlying pulmonary disase. Thus I would gravitate to combination (leflunomide based) non-biologic DMARDS or leflunomide plus rituximab.
(BSRBR Newsletter August 2004 by BSRBR - published in BSR, 2005-08-31)
Session: Managing HBV-Infected RA Patients - Dilemmas and Opportunities
What is the longest survival with HIV and HCV?
Patients successfully treated with HCV who become non-detectable 6 months after starting therapy can lead normal life spans. Since there is no HIV cure many patients successfully treated (for life) who maintain non-detectable virus in their blood can lead normal life spans but not all.
Once you start the antiviral medication, do you like to wait until the virus is neg or simultaneously start the treatment in patients with nml liver numbers?
In the case of HBV it is important to detect "non-detectablity" of HBV-DNA. This may take a few to many weeks depending on how high it is initially.
What are the guidelines regarding steroid use in patients who are hepatitis B or HCV positive?
Steroids in patients with active and untreated HBV (I.e. HBsAG+ + HBV DNA) is dangerous and should be avoided. When HBV DNA is non detectable on therapy it's acceptable.
For HCV there are no data on harmful effects of low dose (Prednisone <20mg QD) steroids.
In case of HCV & rheumatoid arthritis, what is the best treatment with nonbiologic DMARDs & there is some decompensation (child-pugh class B) but active RA? The best evidence is for TNF inhibitors, there is no evidence of decompensation.
ESSENTIAL FACTS ABOUT HCV FOR THE RHEUMATOLOGIST
- Taxonomy: RNA virus member of the Flaviviridaefamily
- Size: 9.6 kb
- Replication rate: In excess of 10 billion particles per day
Epidemiology and transmission
Globally distributed chronic infection
- 170 million infected world wide
- 2.9 million in the USA
Modes of HCV Transmission
- IVDU or intranasal drug use
- Blood products/ tissue transplants before 1992
- High risk sexual activity
- Nosocomial or occupational transmission
- Tattoos, body piercing
- Shared personal items with infected individuals
- Mother to infant
- Most frequently asymptomatic
- 15-40% clear infection within 6 months
- 60-85% chronically infected
- 20% with chronic HCV infection develop cirrhosis leading to hepatocellular carcinoma, decompensation or death
- Chronically infected patients may have normal liver enzymes 30% of the time
- HCV antibody by EIA as initial screen, if positive follow with HCV RNA and if positive patient is chronically infected. If negative patient is probably not infected, repeat RNA testing in 6-12 months.
Session: Treatment of the Patient with Early Rheumatoid Arthritis
What are some examples of regimens using RA drugs in combination?
The two most common are methotrexate and plaquinil and methotrexate, plaquinil and sulfaslazine, both with or without low dose prednisone.
In treating early RA what about cardiovascular risk? What about the infection risk related to DMARD use?
These are great and important questions. Please visit Rheumatology Highlights Report on the CCF website.
Elaine Husni, MD does a terrific job of summarizing CV risk in just 15 minutes: http://www.clevelandclinicmeded.com/online/webcasts/rheumatology-highlights-report/2011-eular/update-rheumatoid-arthritis/
In terms of infections I will steer you to my Rheumatology Highlights report on safety: http://www.clevelandclinicmeded.com/online/webcasts/rheumatology-highlights-report/2011-eular/safety-of-biologic/
When do you use a biologic when adding to or switching therapy? Which agent is used at the onset of the first extraarticular manifestations?
This is a great question. I can't think of a better talk on TNFi failures than that of Ed Keystone, MD at the recent Biologics function at the Cleveland Clinic: http://www.clevelandclinicmeded.com/online/webcasts/biologicsiv/tnf-failures/
In terms of extra-articular features much of this decision is based on which feature you are interested in. For example, tocilizumab sounds logical for anemia because of its effect on inflammation. In terms of diffuse lung disease--this is tough--but I gravitate to rituximab based on recent uncontrolled data suggesting a reasonable safety profile from EULAR.
Session: Treatment Options for the Patient with Refractory RA
Is there information about biologic use (especially TNFi or abatacept) in patients with RA and significant ILD?
There are no comforting data on either of these agents in the presence of ILD. Please see this review for further information: Khasnis AA, Calabrese LH. Tumor necrosis factor inhibitors and lung disease: a paradox of efficacy and risk. Semin Arthritis Rheum. 2010 Oct;40(2):147-163.
Session: Skin Cancer and Biologics: Risks and Management
What is the relationship between treatment with a TNF antagonist and NMSC?
There is a slight increase in incidence of NMSC. This should be monitored clinically and if a patient has a history, yearly skin exams by a dermatologist are advised.
What is the best treatment for a 50 year old woman with RA and an appendicular mass, that was recently diagnosed as an invasive mucinous cyst adenocarcinoma?
Try to avoid biologics if possible and try to treat with triple DMARD therapy.
Session: Early, Aggressive Treatment for Rheumatoid Arthritis: Comparing Combination
biologic to Biologic DMARDs
How long do we continue with the combination therapy?
There is no one correct answer about how long combination therapy should be continued, but 3-6 months duration is an reasonable choice.
How common are rheumatoid arthritis with negative rheumatoid factor?
About one-fourth of patients with RA are rheumatoid factor negative.
Session: Comorbidity in Patients with RA
I am not a rheumatologist and am unfamiliar with DAS28. What is it?
The DAS28 is a standardized measurement of disease activity based on the number of swollen and tender joints, the global assessment of pain (measured on a pain scale), and the ESR. These numbers are entered into a calculator to yield a DAS28 score (range 0 to 10). DAS28 scores are divided into brackets corresponding to disease activity state: low, medium, high, and remission. This measure enables investigators and clinicians to compare responses to treatment.
How long we can administer Methotrexate to a patient with RA safely and effectively?
The use of methotrexate in RA dates back nearly 30 years and there are many patients who take it for this long of a time. The proviso is that the patient is adherent and tolerates therapy, and is monitored properly i.e.. CBC differential, liver enzymes, and albumin every 4 months after initial use. Strong guidelines (ACR) exist for stopping methotrexate when AST rises or albumin falls. Another matter I want to assess in a an aging person who may have started methotrexate at age 50 and who now is over 70 years is renal function. Methotrexate is cleared by the kidney so if GFR falls the methotrexate dose may have to be reduced.
Session: Prevention of Infection in Rheumatoid Arthritis Patients Receiving Biologic Agents
What is the magnitude of infection risk with use of abatacept?
In general, the magnitude of infection risk with abatacept is within the range of the other biologics, about 2-6 cases per 100 patient years. However, long-term safety studies totaling over 10,000 patient years have shown a low incidence of opportunistic infections. Nevertheless, the same safety precautions with regard to infection risk and biologics apply when using abatacept.
Session: Treating a Patient with RA and Hepatitis B or C
Can Sulfasalazine be used in patients with RA and hepatitis B or C?
Good question. Actually there are no data on using sulfasalazine in patients with RA who have hepatitis B or C. It has been suggested, but I still prefer TNF blockers in Childs Pugh A.
Session: Rheumatoid Arthritis and Malignancy
If the patient described in this activity (RA and malignancy, Dr. Latinis) shows worsening disease despite MTX and prednisone, would Rituxan be considered a first line biologic?
Yes, if malignancy becomes an issue regarding TNF inhibitor selection rituximab is generally my second choice. Abatacept is an unknown given lack of data.
What about skin sqamous cell or basal cell cancer in patient with RA? can we use Biologic tx?
Non melanoma skin cancers are common and 'manageable'. I do not believe they are a contraindication from TNF inhibitors. If confronted by a patient with such history, I would send for screening exam per a dermatologist and treat. I would have them have regular 6- 12 month skin screens.
Session: Managing RA Patients with an Inadequate Response to TNF Inhibitors
How long after abatacept would you consider rituximab in a patient with TNF alfa(Enbrel) secondary failure. Note: patient has pulmonary fibrosis. Would you choose adalimumab or tocizilumab instead?
DAS 28 5.2
The presence of IPF confounds this decision. I have strong concerns about abatacept as well as all class TNF inhibitors. Rituximab is logical (although there are no significant data on safety in this population), probably with leflunomide background. The pk of abatacept permits rapid switching.
Session: RA and Heart Failure
In patients with heart failure, acute exacerbation of rheumatoid arthritis poses problems for selection of an effective drug. What would be the best choice of antirheumatic drug?
Although there are strong warnings in the labeling of all TNFi with regards to CHF, it should be noted that the most explicit issues are patients with poorly controlled (Class II or IV) with all agents and especially with higher doses of infliximab. I do not hesitate to use TNFi, especially etanercept in patients 1) requiring a biologic for RA control 2) with well-controlled CHF, and 3) who have had a baseline echocardiogram. Only anecdotes exist for any problem with abatacept and none I am aware of for rituximab.