Arthritis Treatment News: FDA Nixes Expanded Golimumab Use

/ July 27th, 2011/ Posted in Health News / No Comments »

FDA Nixes Expanded Golimumab Use

July 27, 2011 — The US Food and Drug Administration (FDA) did not approve an application for a proposed label expansion for golimumab (Simponi, Janssen Biotech, Inc.), which would include stopping the progression of joint damage. Janssen Biotech, Inc., which is part of Johnson & Johnson, announced Friday that it received a “complete response” letter from the agency.

The “complete response” letter signifies that the FDA has completed its initial review of the application but that changes must be made before the application can be approved.

Brian Kenney, a company spokesperson, would not reveal what additional information the FDA has requested. He also declined to comment on the FDA’s safety concerns.

FDA spokesperson Morgan Liscinsky told Medscape Medical News that federal regulations prevent the FDA from disclosing any information from a new drug application that has not been approved by the agency.

“We look forward to collaborating with the FDA to fully understand the requirements needed to support this proposed label expansion,” Jerome A. Boscia, MD, vice president and head of immunology development at Centocor Research & Development, a division of Johnson & Johnson Pharmaceutical Research & Development, LLC, said in a statement.

Janssen Biotech, Inc., plans to request an end-of-review meeting with the FDA to thoroughly understand the details of the complete response letter and discuss future steps to achieve approval, according to a statement.

The expanded approval application for Simponi sought to expand the physician label to include inhibiting the progression of structural damage, such as joint damage; inducing major clinical response and maintenance of reduction of signs and symptoms; and maintenance of improved physical function in the treatment of moderately to severely active rheumatoid arthritis.

Simponi is a human monoclonal antibody that targets and neutralizes excess anti-tumor necrosis factor (TNF)-α, a protein that can cause inflammation and damage to bones, cartilage, and tissue. It is an FDA-approved treatment for reducing signs and symptoms of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. It is 1 of 5 TNF blockers on the market.

According to David S. Pisetsky, MD, PhD, professor of medicine and immunology in the Division of Rheumatology and Immunology at Duke University Medical Center and director of Duke University Arthritis Center in Chapel Hill, North Carolina, TNF blockers generally do everything listed under Simponi’s proposed label expansion.

“TNF blockers in general fulfill all those criteria,” he told Medscape Medical News after hearing about the application. “But did they have enough data in those particular studies to support those claims?”

The FDA’s initial thumbs down probably relates to a shortage of data from clinical trials to support the claims, he said. It usually relates to the number of patients and duration of the study. “That’s my guess,” he said.

Psoriatic Arthritis

Psoriatic arthritis affects about 25 percent of those with psoriasis and early diagnosis is critical to reduce the risk for joint destruction. Researchers are trying to identify potential markers that may be useful for determining which patients are at greatest risk for the condition.

Psoriatic Arthritis
Psoriasis is a chronic skin condition characterized by red, scaly patches on the skin, typically over the scalp, knees, elbows, and torso. According to the National Psoriasis Foundation, the condition affects about 7.5 million Americans.

Psoriatic arthritis is an inflammatory condition that is sometimes associated with psoriasis. It occurs when the body’s immune system mistakenly attacks the joints. This leads to a breakdown of joint cartilage and bone damage. Christopher Ritchlin, M.D., Rheumatologist with the University of Rochester Medical Center in Rochester, NY, says in addition to bone destruction, psoriatic arthritis patients can have abnormal bone growth, which can cause the joints to fuse and become immobile.

Roughly 25 percent of psoriasis patients develop psoriatic arthritis. Some signs include: painful and swollen joints, back pain, morning stiffness, fatigue, loss of range of motion in the joints, nail changes and redness and pain around the eyes. Most patients develop the condition about ten years after the first signs of psoriasis. However, Ritchlin says about 15 percent of patients develop joint symptoms before the onset of the skin disease and another 15 percent develop the skin and joint symptoms at about the same time.

Getting Treatment
Initial treatment for psoriatic arthritis tends to be conservative. Doctors may start with nonsteroidal anti-inflammatory medications to reduce pain, swelling and inflammation. If these drugs cause too many side effects or fail to reduce symptoms, the next step is to use disease modifying antirheumatic medications, then biologic response modifiers. Exercise is important to keep joints strong and flexible. Patients may also use heat and cold treatments to soothe joint pain.

Ritchlin says patients with psoriatic arthritis often see a dermatologist, rheumatologist and family health care provider. It’s important for all physicians involved in the patient’s care to work together to provide the safest and simplest forms of treatment.

Early diagnosis of psoriatic arthritis is critical to reduce the risk for joint destruction. However, in patients who develop the joint symptoms before the skin disease, Ritchlin says the diagnosis can be tricky because the joint signs may be mistaken for rheumatoid arthritis. Since there are no specific diagnostic tests for psoriatic arthritis, doctors must rely on medical and family history, physical exams, diagnostic X-rays and blood tests (that rule out rheumatoid arthritis). Ritchlin is also looking at potential markers that may be useful for identifying patients at greatest risk for developing psoriatic arthritis.

Shock Wave Therapy and PSGAGs: Effects on Arthritis

We know osteoarthritis (OA) is a painful, degenerative condition that can result in lost training days, poor performance, and early retirement in equine athletes. We also know that there are many different treatments for OA. What we don’t know, and what a team of researchers recently investigated, is how certain arthritic joint tissues–such as the subchondral bone (the layer of bone that lies directly underneath the layer of articular cartilage that lines the ends of the bones and lends support to the joint)–respond to treatments such as extracorporeal shock wave therapy (ESWT) and polysulfated glycosaminoglycans (PSGAGs, a common joint therapy).

“Previous studies have shown that both extracorporeal shock wave therapy and intramuscular administration of polysulfated glycosaminoglycans have a beneficial effect in some horses with OA, and these therapies are widely used in equine practice,” said Chris Kawcak, DVM, PhD, Dipl. ACVS, professor and equine surgeon at the Gail Holmes Equine Orthopaedic Research Center at Colorado State University.

“The subchondral bone is commonly involved in joint disease and is therefore a potential site of action for ESWT and PSGAGs,” relayed Kawcak.

To determine if ESWT or PSGAGs “targeted” the subchondral bone, Kawcak and colleagues created a chip in the middle carpal joint (the lower joint in the knee) in one knee of 24 healthy horses. Three groups of horses were then either treated with ESWT, PSGAGs, or neither. The team evaluated the treatment results by measuring the levels of various markers of cartilage and bone turnover (i.e., synthesis and degradation) in blood and synovial (joint) fluid samples; evaluating bone density; and assessing the structure and composition of the bone.

Key findings of the study were:
PSGAG had no significant effect on any bone variables; and
ESWT also did not affect the subchondral bone itself, but increased levels of the bone marker called osteocalcin in the blood were significantly higher in horses treated with ESWT than in the control group.

“Unlike other published studies, we did not find any physical evidence of subchondral bone remodeling, and, thus, healing following either ESWT or PSGAG administration,” relayed Kawcak.

Comments are closed.