Neck Pain from Rheumatoid Arthritis – Subcutaneous Abatacept gets FDA Approval

abatacept neck pain rheumatoid arthritis fda approvalSevere neck pain can be caused by rheumatoid arthritis and so the approval by the FDA of subcutaneous abatacept will be welcome news for those suffering from chronic neck pain related to the autoimmune disease. Along with neck pain and more widespread joint pain, rheumatoid arthritis can cause extreme fatigue, fever, and even lead to spinal stenosis from degeneration of the joints in the spine. In extreme cases, particularly where a patient with rheumatoid arthritis has also experienced whiplash, the disease which involves the immune system erroneously attacking the body’s own joint tissue, can lead to spinal cord compression from changes in the position of the spine. Atlantoaxial subluxation may occur at the top of the spine where the skull meets the spinal column, causing myelopathy. Finding an effective treatment to put rheumatoid arthritis into remission would help reduce such events and the research supporting abatacept’s approval by the FDA suggests that patients finding little benefit from existing treatments may yet have cause for hope.


Abatacept (the brand name is Orencia) has been approved by the Food and Drug Administration for the treatment of adults with moderate-to-severe RA, allowing patients to inject the formulation themselves at a fixed dose once a week. There is also an initial dose taken intravenously (in most cases) for the purpose of loading, which amounts to 10mg/kg of body weight for most patients. Each weekly subcutaneous self-injectable dose is then 125mg.

The approval of abatacept (a biologic medication) for rheumatoid arthritis gives physicians the option of prescribing a non-anti tumor necrosis factor (TNF) medication alongside the new drug that has a different mechanism. The lead investigator of the study on which the drug’s approval heavily rests is Mark C. Genovese of Stanford University Medical Center. Genovese stated that subcutaneous abatacept “demonstrated efficacy and safety consistent with the intravenous formulation.” Patients unable to have the intravenous dose may start on the weekly injections of subcutaneous abatacept without the initial loading dose. The drug is the first biologic for RA that is available as a subcutaneous formulation and in an intravenous form although it should not be used at the same time as TNF antagonists, making it inappropriate for some patients.

The Evidence for Abatacept

Clinical trial results for abatacept compared the subcutaneous formulation alone to the drug in addition to TNF antagonists, with clear differences in safety. No additional benefits were observed taking both medications together but the rate of infection was higher at 63% (versus 43%) in the combination group and serious infections were also higher at 4.4% compared to 0.8%. Intravenous abatacept had a slightly higher rate of malignancy associated with it compared to placebo (1.3% compared to 1.1%), and a higher rate of serious infection at 3% compared to 1.9% with the placebo.


The use of abatacept offers hope to patients of reducing pain (including neck pain from rheumatoid arthritis), along with improvements in physical function, and a slowing down of the degeneration of joint structures and tissues. In another study, by Yazici et al (2011), researchers at New York’s University Hospital for Joint Diseases found that patients with early stage RA were more likely to have their RA go into remission with abatacept treatment in comparison to those with long-standing disease. The patients in this trial, who had experienced no significant relief with methotrexate treatment, had had RA for less than two years in 23% of cases or longstanding RA of more than ten years’ duration. At the one-year mark, abatacept had resulted in remission of rheumatoid arthritis in 35.2% of patients with early disease compared to 19.4% of the second group, rising to 46.0% vs. 30.9% at year 3. The authors suggest that patients who do not respond to methotrexate treatment early in the course of their therapy may benefit instead from treatment with abatacept.

Abatacept Prescription Guidelines

Not all patients with rheumatoid arthritis are likely to be prescribed the new subcutaneous abatacept treatment however, and guidelines for doctors may include advice to test patients’ CD28-negative T Cells prior to administering the medication. It appears that those with high circulating levels of these immune system cells are less likely to respond well to abatacept treatment, according to a study by Scarsi, et al (2011). This Italian study looked at thirty-two patients, all with rheumatoid arthritis and all treated with abatacept. After six months of abatacept therapy the researchers found that patients with low baseline numbers of CD8+CD28- T Cells had more than four times the likelihood of achieving RA remission than patients with higher levels of these cells.

abatacept orencia neck pain rheumatoid arthritis approvalAnother study that took place in Italy examined the cost-effectiveness of abatacept for treating rheumatoid arthritis patients. Again, the patients that took part in the study were non-responders to treatment with anti-TNF agents and Cimmino (et al, 2011) found that abatacept was more effective than rituximab in achieving a state of low disease activity (LDAS) over two years with the former group enjoying 102 days LDAS compared to just 82 days LDAS with rituximab. The cost of treatment was advantageous when abatacept was used after just one or two anti-TNF agents rather than attempting a third such medication prior to prescribing abatacept. Indeed, using abatacept after two anti-TNF agents was significantly more effective than using a third anti-TNF agent, with sixty-three days of low disease activity compared to thirty-two days respectively. Such research is also likely to influence the guidelines for prescribing the biologic agent for rheumatoid arthritis patients as they appear able to reduce healthcare costs alongside improving a patient’s condition.

Patients currently taking methotrexate for neck pain and more widespread symptoms of rheumatoid arthritis may also be able to benefit from additional abatacept therapy as well as those who have not responded to methotrexate treatment alone. A clinical trial carried out in New York (NCT00122382) found improved LDAS and inhibition of progression of erosive rheumatoid arthritis in patients given abatacept and methotrexate together and with abatacept added to methotrexate treatment after one year, with the former experiencing the better overall results. This two-year study, completed by 433 patients, found that 55.2% were in remission at the end of the trial having taken the two rheumatoid arthritis medications together. Those in the methotrexate alone group for the first year who then had abatacept added to their treatment programme had an increased rate of remission from 26.9% to 44.5% on one measure, and 60.4% from 43.2% on another (LDAS). Bathon, et al (2011), note that the safety issues appeared similar in each group, with similar rates of infections and autoimmune events.

The approval by the FDA of abatacept as a novel therapy for rheumatoid arthritis will be welcomed by the vast number of patients suffering from the disease who find that current medications fail to adequately relieve their symptoms. With the drug administered by the patient the costs of treatment are reduced, making it easier on healthcare budgets in addition to helping patients. Although neck pain can be caused by a number of factors, rheumatoid arthritis can be particularly hard to manage as it may progress unchecked in some patients. FDA approval of abatacept gives patients and their physicians another weapon in the armory against the painful autoimmune disease.


References

Yazici Y, Moniz Reed D, Klem C, Rosenblatt L, Wu G, Kremer JM., Greater remission rates in patients with early versus long-standing disease in biologic-naive rheumatoid arthritis patients treated with abatacept: a post hoc analysis of randomized clinical trial data. Clin Exp Rheumatol. 2011 May-Jun;29(3):494-9. Epub 2011 Jun 29.

Scarsi M, Ziglioli T, Airo’ P., Baseline Numbers of Circulating CD28-negative T Cells May Predict Clinical Response toAbatacept in Patients with Rheumatoid Arthritis. J Rheumatol. 2011 Aug 1.

Cimmino MA, Leardini G, Salaffi F, Intorcia M, Bellatreccia A, Dupont D, Beresniak A., Assessing the cost-effectiveness of biologic agents for the management of moderate-to-severe rheumatoid arthritis in anti-TNF inadequate responders in Italy: a modelling approach. Clin Exp Rheumatol. 2011 Jul 26.

Bathon J, Robles M, Ximenes AC, Nayiager S, Wollenhaupt J, Durez P, Gomez-Reino J, Grassi W, Haraoui B, Shergy W, Park SH, Genant H, Peterfy C, Becker JC, Covucci A, Moniz Reed D, Helfrick R, Westhovens R., Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated withabatacept: 2-year outcomes. Ann Rheum Dis. 2011 Aug 6.

Caution

It is important to note that abatacept, like most medications, can cause side-effects. As the approval of the drug for use in rheumatoid arthritis is very recent it may be that the listed side-effects are not exhaustive and patients should report any concerns to their physician immediately.

Common abatacept side-effects include: Dizziness; headache; mild pain, swelling, or redness at the injection site; mild sore throat; nausea; stomach upset; stuffy nose.

More severe side-effects of abatacept include: Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chills, fever, or persistent sore throat; flu-like symptoms; increased cough; increased, decreased, or painful urination; night sweats; severe or persistent dizziness; shortness of breath; unexplained weight loss; unusual lumps or growths; unusual tiredness; wheezing.


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