North carolina rheumatology association

North Carolina Rheumatology Association
Position Statements
Appropriate delivery, handling, storage and administration of biologic agents Treatment in patients unable to tolerate routine therapy I-A: Appropriate Delivery, Handling, Storage and
Administration of Biologic Agents

Statement: The North Carolina Rheumatology Association believes that the standard of care for the
administration of biologic agents for autoimmune inflammatory rheumatic diseases requires
rheumatologist recommendations for the choice of medication as well as rheumatologist approval of
the handling, delivery, storage and administration of intravenously administered medications when
infusions are performed in their offices.
Discussion: In the last decade there have been numerous discoveries that have lead to a better
understanding of the pathogenesis of rheumatoid arthritis. As a result of these discoveries, agents that
modify specific abnormalities of the immune system, termed biologic agents, have been developed. The
use of these agents in the treatment of rheumatoid arthritis and other autoimmune diseases has resulted in a
marked improvement of the overall condition of people with these illnesses. According to some studies it is
now possible to even prevent deformities and resultant disabilities in illnesses like rheumatoid arthritis.
Biologic agents target interleukins and cytokines, which are involved in disease pathogenesis and
inflammation. For the treatment of rheumatoid arthritis the FDA has approved the use of infliximab,
etanercept, anakinra and adulimumab. These medications have been shown, in clinical trials, to have a
dramatic impact on disease activity by reducing joint swelling, pain, and stiffness. Several of these
medications (infliximab, etanercept and adulimumab) have additionally been shown to reduce joint
erosions and joint space narrowing which lead to joint destruction, deformities and disability. Use of these
agents not only improves short-term disease activity and symptoms but also improves long-term outcomes
by preserving quality of life, decreasing disability and avoiding the need for joint replacement surgery and
perhaps even long term care.
There are many therapeutic alternatives for the treatment of rheumatoid arthritis. A rheumatologist, with
patient involvement, must consider age, gender, length and severity of illness, and other medical history in
determining the appropriate medication for that specific patient. The North Carolina Rheumatology
Association believes that the choice of biologic agents for the treatment of rheumatoid arthritis is the
responsibility of the treating rheumatologist and the patient based on standard of care issues.
Additionally, in-office infusion of intravenous biologic agents is extremely safe and highly cost-
effective in the hands of rheumatologists. This is similar to the current policies established for physicians
specializing in Oncology, who have been utilizing in-office infusion of chemotherapy for many years.
These medications require appropriate handling and delivery. Without appropriate refrigeration and
handling, these medications can be denatured or damaged. If denatured, more serious side effects may
occur during infusion or administration. It is therefore imperative that the delivery of these medications
also remains acceptable to established standards of care for biologic agents. This is of extreme importance
in biologic agents requiring intravenous infusion.
The intravenous infusions of biologic agents can be associated with potentially serious side effects,
including: pruritus, rash, headache, dyspnea, chest pain, hypertension, hypotension and even anaphylactic
reactions. It is imperative that this medication be given in a controlled environment with experienced staff
present knowledgeable of the patient’s complicated medical history, aware of the potential side effects of
the infused biologic agents and competent in the management of potential adverse events. Under these
conditions, patient acceptance and confidence is increased, compliance is assured, outcomes are optimized
and efficiency is maximized.
I-B: Biologic Agents – Indications for Use

Statement: The North Carolina Rheumatology Association believes that the use of biologic
agents (infliximab, etanercept, anakinra and adulimumab) for the treatment of patients
with serious autoimmune diseases (e.g. psoriatic arthritis, ankylosing spondylitis,
inflammatory eye disease, Behcet’s disease) is appropriate in those who do not respond to
other therapies or are not candidates for other therapies available and is the standard of
care when patholophysiologic evidence and published information for efficacy exists and
supports the use of these agents. To interfere with this prudent, reasonable and cautious
treatment of patients represents an interference with the standard of care for patients in
need of serious disease treatment in a timely manner These treatments should be quickly
approved and available through health insurers when a rheumatologist has concluded that
treatments with these agents are necessary.

Discussion: In the last decade, increased knowledge of cytokine activation and interactions has lead to a
better understanding of the pathogenesis of rheumatoid arthritis, psoriatic arthritis, and other autoimmune
inflammatory diseases. As a result of these discoveries and the development of biologic agents to inhibit
cytokine activities, a marked improvement in control and prevention of progression is now possible in
many diseases. FDA approval of these and other medications for specific indications are recognized as
guidelines for the pharmaceutical industry and are not intended to restrict medical use where appropriate.
Pathophysiologic mechanisms in other serious, uncommon and rare diseases warrant use of these agents
especially where academic experience, published information and/or scientific information is confirmatory.
For example, infliximab (Remicade) and etanercept are biologic agents targeting tumor necrosis factor, a
key cytokine in immune mediated inflammatory diseases. The FDA has approved these agents for use in
the treatment of rheumatoid arthritis, psoriatic arthritis and, in the case of infliximab, for Crohn’s disease.
Other indications are pending FDA approval. This medication has been shown in numerous clinical studies,
as published in scientific journals and published at scientific meetings, to have a dramatic impact on the
disease activity of many other conditions not responsive to other therapies including psoriasis, ankylosing
spondylitis, inflammatory eye disease, Reiter’s syndrome and Behcet’s syndrome. Improvement in joint,
skin and destructive organ involvement is observed in these respective diseases when treated with
infliximab. Improvement in short-term disease activity with preservation of function, low risk and long-
term quality of life (potentially resulting in less disability, decreased need for joint replacement surgery,
decreased skin scarring, preservation of vision and probably decreased mortality due to other disease
complications and comorbid conditions) are possible with these treatments (references available upon
request).
Biologic agents need to be available when therapeutic alternatives for the treatment of psoriasis, psoriatic
arthritis, ankylosing spondylitis, inflammatory eye disease, and Behcet’s disease fail or are not indicated.
The FDA has approved the use of etanercept for the treatment of psoriatic arthritis however availability has
not been reliable. No other biologic agents have received FDA approval for treatment of psoriasis,
ankylosing spondylitis, autoimmune inflammatory eye disease, or Behcet’s disease. Infliximab has been
shown in many clinical studies to have significant benefit in psoriasis, ankylosing spondylitis,
inflammatory eye disease, and Behcet’s disease.
A rheumatologist, with the agreement of the patient, must consider a patient’s age, gender, length and
severity of illness, potential complications of alternate therapies, comorbid conditions and other medical
history in determining the appropriate medication for management. To abrogate or impair this decision
making capacity of Rheumatologists is indicative of a denial to accept the standard of care as set forth by
the North Carolina Rheumatology Association.
II-A. Osteoporosis Treatment in patients unable to tolerate routine therapy
Statement: The North Carolina Rheumatology Association recommends that
intravenous bisphoshonate therapy, when prescribed by rheumatologists after
thorough evaluation, be available, utilized and appropriately reimbursed by health
insurers for the treatment of osteopenia, osteoporosis, and/or low-trauma fractures
(fragility fractures), in appropriate patients who cannot tolerate or are refractory to
treatment with estrogen replacement therapy, raloxifene (Evista), alendronate
(Fosamax) or risedronate (Actonel). Use of parenteral bisphoshonates is also not
inappropriate in these same patients after successful treatment with teraperitide.
We believe that this represents the standard of care for these seriously ill patients.
Discussion: The NIH Consensus Statement on Osteoporosis Prevention, Diagnosis, and
Therapy defines osteoporosis as "a skeletal disorder characterized by compromised bone
strength predisposing to an increased risk of fracture. Bone strength reflects the
integration of two main features: bone density and bone quality." Osteoporosis is a silent
disease until bones become so weak that fractures occur. Osteoporosis is a major health
problem in the United States, affecting approximately 10 million people. Approximately
18 million people have osteopenia. One of every three women over the age of 50 have
osteoporosis and nearly half of all women over 50 will break a bone in her lifetime due to
osteoporosis. Approximately one in every eight men over the age of 50 will have an
osteoporotic fracture in his lifetime. Ultimately, in an extremely elderly population, one
in every six men will have a hip fracture.
Appropriate therapeutic alternatives for the prevention and treatment of osteoporosis
include calcium, vitamin D, estrogen replacement therapy, raloxifene (Evista),
alendronate (Fosamax), risedronate (Actonel), calcitonin (Miacalcin) and teraperitide
(Forteo). Unfortunately, some patients have contraindications to taking these
medications, develop intolerable side effects, or are refractory to therapy. An alternative
to these routine medications is intravenous bis-phosphonate therapy, such as pamidronate
(Aredia). Pamidronate has been shown to inhibit bone resorption and improve bone
density in patients with osteoporosis.
II-B. Osteoporosis Evaluation in Men
Statement: The North Carolina Rheumatology Association recommends that central
DEXA studies be performed and appropriately reimbursed by insurance, for these
additional conditions: 1) testosterone deficiency (257.2?); 2) men over the age of 70
(code?); 3) men receiving hormonal therapy for the treatment of prostate cancer
(V58.69?); 4) men with any low trauma fracture (codes?); and 5) men with
rheumatoid arthritis (714.0) and other autoimmune inflammatory diseases.
Discussion: The NIH Consensus Statement on Osteoporosis Prevention, Diagnosis, and
Therapy defines osteoporosis as "a skeletal disorder characterized by compromised bone
strength predisposing to an increased risk of fracture. Bone strength reflects the
integration of two main features: bone density and bone quality." Osteoporosis is a silent
disease until bones become so weak that fractures occur. Osteoporosis is a major health
problem in the United States, affecting approximately 10 million people -20% of who are
men. Approximately 18 million people have osteopenia –approximately 20% of who are
men. Thirty percent of all hip and vertebral fractures occur in men. Approximately one
in every eight men over the age of 50 will have an osteoporotic fracture in his lifetime.
Ultimately, in an extremely elderly population, one in every six men will have a hip
fracture.
Osteoporosis in men has become a major health problem as the elderly population
expands. In men, bone density declines slowly after 30 years of. A number of risk
factors increase the chance of developing osteoporosis and fractures in men, including:
smoking, excessive alcohol consumption, the use of corticosteroids and certain anti-
seizure medications, inadequate intake of calcium and vitamin D, inadequate exercise, a
family history of osteoporosis, and a previous history of low trauma fracture (hip, wrist,
pelvis, etc.). Illnesses such as hyperthyroidism, hyperparathyroidism, and severe liver
and kidney diseases can lead to osteoporosis. In men, the lack of testosterone and the use
of some treatments for prostate cancer (e.g., Lupron) can also result in osteoporosis.
Additionally, rheumatoid arthritis can increase bone resorption and can lead to metabolic
bone disease.
Osteoporosis, in both men and women, is best diagnosed with a central bone density test,
called a DEXA. Although both central and peripheral bone density tests can identify
patients with osteoporosis or osteopenia, central DEXA studies are recognized as the only
way to monitor response to therapy. Moreover, the World Health Organization
definitions of disease prevalence using T-score equivalents are based on central, not
peripheral, DEXA measurements.
Medicare and other insurance companies generally cover central DEXA studies in men
for the following diagnoses: osteopenia (733.90), osteoporosis (733.00 – 733.09),
hyperparathyroidism (252.0), vertebral fracture (733.13), or for monitoring of bone
density when on chronic corticosteroids (V58.69) or monitoring response to therapy
(V67.59).
III. Cox-2 Drugs

Statement: It is inappropriate to apply the same restrictions, review processes and
scrutiny to subspecialty Rheumatologists prescribing Cox 2 or other NSAID
medications as those used to review, restrict or scrutinize other specialists. The
North Carolina Rheumatology Association strongly recommends alteration of the
review processes and restrictive processes for Rheumatologists prescribing any and
all anti-inflammatory agents for the care of patients with serious inflammatory
rheumatic diseases. To continue to do otherwise is counter-productive, costly,
inappropriate and harmful to patient care.
COX 2 anti-inflammatory medications represent a significant advance in rheumatology
therapeutics with markedly decreased GI toxicity compared to previously available
agents. Appropriate selection of anti-inflammatory agents for chronic uses in
inflammatory rheumatic diseases is complicated given other existing comorbid
conditions, use of concomitant medications prescribed by other physicians, patient age
and patient debility. This medical decision making process differs significantly from
NSAIDs selection for short-term use in acute musculoskeletal traumas and injuries,
minor, short term arthritic problems or for other non-rheumatic purposes by other
specialists.

Source: http://www.allianceforpatientaccess.org/wp-content/uploads/2013/12/example_position_statements_from_nc_rheumatology_assoc.pdf