Orencia Reviews

qqkingdom 2014-04-08

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Orencia Side Effects & Safety

Abatacept (Orencia) is called a costimulation modulator that inhibits T-cells (T lymphocytes), which play a key role in the immune response involved in RA. It is manufactured by Bristol-Myers Squibb and is indicated (approved for use) for the treatment of moderately- to severely-active RA in adults as monotherapy (used alone) or in combination with disease-modifying anti-rheumatic drugs (DMARDs) other than anti-TNF treatments. It is also approved for the treatment of juvenile idiopathic arthritis.

Abatacept (Orencia): overview and efficacy

Abatacept (Orencia) is called a costimulation modulator that inhibits T-cells (T lymphocytes) which play a key role in the immune response involved in RA. It is manufactured by Bristol-Myers Squibb and is indicated (approved for use) for the treatment of moderately- to severely-active RA in adults as monotherapy (used alone) or in combination with disease-modifying anti-rheumatic drugs (DMARDs) other than anti-TNF treatments. It is also approved for the treatment of juvenile idiopathic arthritis.¹

How is Orencia taken?

Orencia is given either as an intravenous (IV) infusion or as a subcutaneous injection (under the skin). If Orencia is given by IV infusion, treatment starts with an IV loading dose of 8-10 mg per kg of body weight (500-1000 mg), given at week 0, 2, and 4, followed by monthly infusions at the same dosage. An IV infusion of Orencia typically takes about 30 minutes.

If Orencia is given as a subcutaneous injection, treatment may be started with or without an IV loading dose (as above). If the IV loading dose is given, a subcutaneous injection of 125 mg is given within a day of the loading dose, then once weekly, thereafter. If no IV loading dose is given, then subcutaneous injections of Orencia 125 mg are given once weekly.¹

If you decide to give yourself the Orencia injection at home, you (or a caregiver) should receive training on the correct way to prepare and administer the injection. Do not give yourself an injection of Orencia until your doctor or nurse has shown you how to do it. Remember to read the “Instructions for Use” that come with your Orencia prefilled syringe packet. If you have any questions about how to administer Orencia, call your doctor or pharmacist or call the patient support line at 1-800-ORENCIA (1-800-673-6242).

How does Orencia work?

Orencia is called a costimulation modulator because it binds to two proteins (CD28 and CD80/86) found on the surface of B-cells and other lymphocytes that together provide the costimulatory signal to fully activate T-cells. So, in this manner abatacept inhibits the function of T-cells, which play a key role in the immune response involved in RA. In addition to decreasing the production of T-cells, abatacept also inhibits the production of a number of cytokines that also play a role in RA, including tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN- γ), and interleukin-2 (IL-2).¹

Are there people who should not take Orencia?

There is an increased risk for serious infections with Orencia. This is because Orencia can decrease the ability of the immune system to fight infections. If you are taking Orencia and you develop a serious infection, contact your doctor immediately. You may need to interrupt or discontinue the drug.¹

Orencia is a pregnancy category C drug. In animal studies, while Orencia did not result in birth defects in the developing fetus, there were changes in immune function. There have been no well-controlled studies in humans. Orencia should only be used in pregnant women if the potential benefits justify the risk to the fetus.¹

It is unknown whether Orencia is excreted into human milk. Because of the potential for adverse effects to the nursing infant, a nursing woman should either stop taking the drug or discontinue nursing while taking Orencia.¹

What evidence do we have that Orencia works in RA?

The effectiveness of IV Orencia in RA has been evaluated in six randomized, controlled trials in adult patients with active RA. Five of these studies included patients with moderately- to severely-active RA. The remaining study made no requirement for number of tender or swollen joints in its inclusion criteria. In five studies, patients were randomized to IV Orencia given at weeks 0, 2, and 4, then every 4 weeks thereafter. Another study was conducted to evaluate Orencia given as a subcutaneous (SC, or subQ) injection, randomizing 1,457 patients who had had an inadequate response to methotrexate to either IV or SC Orencia, with methotrexate continued.¹

Study 1 (IV) was conducted in patients who had failed at least one conventional DMARD or the biologic etanercept (Enbrel). Study 3 (IV) was conducted in patients who had had an inadequate response to the DMARD methotrexate. Study 4 (IV) was conducted in patients who had had an inadequate response to a tumor necrosis factor-alpha inhibitor (anti-TNF-α). Finally, Study 6 was conducted in patients who had never been treated with methotrexate.¹

Disease control and clinical response. Orencia combined with conventional DMARDs resulted in higher rates of ACR20, 50, and 70 response than the combination of placebo and DMARDs across the IV studies. These higher response rates were maintained through 12 months. In one open-label extension, response rates were maintained for up to 3 years. In the single study (Study 1) in which Orencia was given alone as monotherapy, it also resulted in higher rates of ACR20, 50, and 70 response at 3 months. In the study evaluating Orencia subQ dosing (combined with methotrexate), rates of ACR20, 50, and 70 response were similar to those achieved with IV dosing (combined with methotrexate).¹

Clinical responses in clinical studies of Orencia in RA
	Inadequate response to DMARDs		Inadequate response to MTX		Inadequate response to anti-TNF		MTX-naive
	Study 1		Study 3		Study 4		Study 6
	Orencia (N=32)	Placebo (N=32)	Orenciab + MTX (N=424)	Placebo + MTX (N=214)	Orenciab + DMARDs (N=256)	Placebo + DMARDs (N=133)	Orenciab + MTX (N=256)	Placebo + MTX (N=253)
ACR20
Mon 3	53%	31%	62%*	37%	46%*	18%	64%**	53%
Mon 6	–	–	68%*	40%	50%*	20%	75%***	62%
Mon 12	–	–	73%*	40%	–	–	76%*	62%
AC50
Mon 3	16%	6%	32%*	8%	18%***	6%	40%*	23%
Mon 6	–	–	40%*	17%	20%*	4%	53%*	38%
Mon 12	–	–	48%*	18%	–	–	57%*	42%
ACR70
Mon 3	6%	0%	13%*	3%	6%**	1%	19%***	10%
Mon 6	–	–	20%*	7%	10%***	2%	32%***	20%
Mon 12	–	–	29%*	6%	–	–	43%*	27%
Major clinical Mon 12c	–	–	–	–	–	–	41%*	23%
Statistical significance: P<0.001 versus placebo group. Statistical significance: P<0.05 versus placebo group. **Statistical significance: P<0.01 versus placebo group. ^aOrencia given at 10 mg/kg. ^bOrencia dosing based on weight range. ^cMajor clinical response defined as continuous ACR70 response maintained for 6 month period.

Radiographic progression. X-rays were taken in Studies 3 and 6 to evaluate structural changes from baseline (at the start of the study) using the Genant-modified Total Sharp Score. Orencia + methotrexate resulted in a significant decrease in the progression of structural damage at 1 year compared with placebo + methotrexate.¹

Radiographic change from baseline to 1 year in Orencia Studies 3 and 61
Mean scores	Orencia + MTX	Placebo + MTX
Study 3
Total Sharp-Genant Score	1.07*	2.43
Erosion score	0.61*	1.47
Joint space narrowing score	0.46*	0.97
Study 6
Total Sharp-Genant Score	0.6**	1.1
Statistical significance: P<0.01 versus placebo + methotrexate (MTX). *Statistical significance: P=0.04 versus placebo + MTX.