Impact of Rheumatoid Arthritis Goes Beyond Signs and Symptoms, Delay in Treatment May Impact Long-Term Employment

WASHINGTON, November 13 /PRNewswire/ --

- Pooled Analysis of More Than 1,400 Patients from Two Pivotal Rheumatoid Arthritis Trials Showed Disease Duration and Physical Function Were Related to Probability of Employment

According to data presented today at the American College of Rheumatology (ACR) Annual Scientific Meeting, women and men (average age of 45 years) with rheumatoid arthritis (RA) who have sustained, moderate disability have similar reductions in the probability of employment and full-time employment. From the analysis, investigators concluded that physical function and disease duration are important factors associated with lack of employment in RA and that improving physical function and treating patients earlier may have a substantial impact on work disability. RA is the most common form of inflammatory arthritis, affecting more than two million Americans and about 75 percent of those affected are women.(1)

"The ATTRACT and ASPIRE trials showed that intervention with REMICADE (infliximab), in combination with methotrexate, reduced the signs and symptoms, inhibited joint damage, and improved physical function in patients with moderately to severely active RA," said Josef Smolen, MD, Professor of Internal Medicine and Chairman of the Department of Rheumatology of Vienna General Hospital, and investigator in both studies. "Importantly, these latest analyses, based on patient characteristics at enrollment in these trials, offer further insight on how the burden of this disease relates to the probability of employment for women and men living with RA."

According to a multiple regression analysis of data from the ATTRACT and ASPIRE studies, which evaluated more than 1400 patients with active RA, employment was statistically significantly associated with physical function, age, gender or disease duration at baseline. A regression model showed that for a 45-year-old woman with RA with sustained moderate disability (defined as a Health Assessment Questionnaire score of 1.5), the probability of employment decreased from 0.63 to 0.56 to 0.48 to 0.40 after five, 10 and 15 years of disease onset, respectively. For full-time employment, the probability decreased from 0.48 to 0.38 to 0.28 to 0.20 at five-year intervals over the course of 15 years.

For a man of the same age, disability level and disease duration, the probability of being employed decreased from 0.69 to 0.62 to 0.54 to 0.46 after five, 10 and 15 years of disease onset, respectively. The model also showed that the probability of full-time employment for a man decreased from 0.64 to 0.55 to 0.43 to 0.33 at five-year intervals over the course of 15 years. The difference in employability between women and men after the 15 years was similar to baseline differences seen between the genders. HAQ scores of 0 to 1 are generally considered to represent mild to moderate difficulty, 1 to 2 moderate to severe disability and 2 to 3 severe to very severe disability. Average scores that have been reported in a population-based study are 0.49, and in RA patients are 1.2.(2)

About ATTRACT

The Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) study included 428 patients at 34 research centers in North America and Europe. All patients had moderately to severely active RA despite taking methotrexate. To enter the study, patients had to have at least six swollen joints (out of 66) and six tender joints (out of 68). Also, patients had X-rays of their hands and feet to look for evidence of joint damage. Blood samples were taken to look for rheumatoid factor or for high levels of C-reactive protein, which is a sign of inflammation. Many patients were taking other medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids. Patients were randomized to receive REMICADE 3 mg/kg or 10 mg/kg plus methotrexate or placebo plus methotrexate at weeks 0, 2 and 6 and then every eight weeks thereafter through week 102.

During the ATTRACT study, the incidence of side effects was similar for patients treated with REMICADE and methotrexate and with placebo and methotrexate. The most frequently reported side effects were upper respiratory tract infection, headache, nausea, sinusitis and rash. The incidence of serious side effects was low and was similar in patients treated with REMICADE and methotrexate and with placebo and methotrexate. The most frequent serious adverse event that occurred in patients treated with REMICADE and methotrexate was pneumonia. Please see "Important Safety Information" below.

About ASPIRE

The Active-Controlled Study of Patients Receiving Infliximab for Treatment of Rheumatoid Arthritis of Early Onset (ASPIRE), the largest controlled trial ever conducted exclusively in RA patients with early disease, found REMICADE plus methotrexate to be superior to placebo and methotrexate in patients with moderately to severely active disease. ASPIRE was a 54-week, randomized, double blind, active control study involving 1,004 patients with early disease enrolled in 125 centers in North America and Europe. At randomization, all patients received methotrexate and either placebo, REMICADE 3 mg/kg or REMICADE 6 mg/kg at weeks 0, 2 and 6 and then every eight weeks thereafter. The ASPIRE trial demonstrated superiority of the REMICADE and methotrexate regimen over placebo and methotrexate on all three primary endpoints, including reduction of signs and symptoms, inhibition of the progression of structural damage and improvement in physical function.

During the ASPIRE study, the most commonly reported adverse events were upper respiratory infection, nausea and headache. Serious infections included pneumonia, tuberculosis and sepsis. Please see "Important Safety Information" below.

About Rheumatoid Arthritis

RA is a chronic, progressive disease and research suggests that a critical therapeutic window may exist within the first two years of disease onset when the rate of radiographic progression of the disease can be "reset."(3)(4)(5) Radiographic changes occur within two years of disease onset in 50-70 percent of RA patients.(6) The American College of Rheumatology (ACR) suggests control of disease progression should start early to limit joint damage in RA.(5) RA is associated with substantial disability and economic losses, and one study showed that one-third of patients in the UK who were employed became work-disabled within two years of disease onset.(7) Rheumatologic disorders also account for 25 percent of Social Security disability payments.(8)

About REMICADE

REMICADE is a monoclonal antibody that specifically targets TNF-alpha, which has been shown to play a role in Crohn's disease (CD), rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), ulcerative colitis (UC), pediatric Crohn's disease (PCD) and psoriasis (PsO). REMICADE is the global market leader among anti-tumor necrosis factor alpha (TNF-alpha) therapies and the only agent approved for the treatment of both RA and CD in North America, the European Union (EU) and Japan. Additionally, REMICADE is the only anti-TNF approved in three different therapeutic areas: gastroenterology, rheumatology and dermatology. The safety and efficacy of REMICADE have been well established in clinical trials over the past 14 years and through commercial experience with more than 840,000 patients treated worldwide.

In the U.S., REMICADE, in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage and improving physical function in patients with moderately to severely active RA. REMICADE is the only biologic indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult and pediatric patients with moderately-to-severely active CD who have had an inadequate response to conventional therapy. REMICADE is also indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in patients with fistulizing CD. In December 2004, REMICADE was approved for reducing signs and symptoms in patients with active AS. In May 2005, REMICADE was approved for reducing signs and symptoms of active arthritis in patients with PsA. Additionally, in September 2005, REMICADE was approved for reducing signs and symptoms, achieving clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately to severely active UC who have had an inadequate response to conventional therapy. This approval makes REMICADE the first and only biologic approved for the treatment of moderate to severe UC. In May 2006, REMICADE was approved for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy. This approval establishes REMICADE as the first and only biologic therapy approved for the treatment of PCD. In August 2006, REMICADE was approved for inhibiting progression of structural damage and improving physical function in patients with psoriatic arthritis. In September 2006, REMICADE was approved for the treatment of adults with chronic, severe (i.e. extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. In October 2006, REMICADE was approved for maintaining clinical remission and mucosal healing in patients with moderately to severely active UC, who have had an inadequate response to conventional therapy.

In the EU, REMICADE is indicated for the treatment of severe, active CD in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. REMICADE also is indicated for the treatment of fistulizing, active CD in patients who have not responded despite a full and adequate course of therapy with conventional treatment (including antibiotics, drainage and immunosuppressive therapy).

For RA patients in the EU, REMICADE, in combination with methotrexate, is indicated for the reduction of signs and symptoms as well as the improvement in physical function in patients with active disease when the response to disease-modifying drugs, including methotrexate, has been inadequate, and in patients with severe, active and progressive disease not previously treated with methotrexate or other DMARDs. In these patient populations, a reduction in the rate of the progression of joint damage, as measured by X-ray, has been demonstrated. In carefully selected patients with RA who have tolerated three initial two-hour infusions of REMICADE, consideration may be given to administering subsequent infusions over a period of not less than one hour.

In the EU, REMICADE is also indicated for the treatment of AS in patients who have severe axial symptoms, elevated serological markers of inflammatory activity and who have responded inadequately to conventional therapy. REMICADE is also approved for the treatment of active and progressive PsA in adults when the response to previous disease-modifying anti-rheumatic therapy. REMICADE should be administered in combination with methotrexate or alone in patients who show intolerance to methotrexate or for whom methotrexate is contraindicated. REMICADE is also approved in the EU for the treatment of moderate to severe plaque psoriasis in adults who failed to respond to, or have a contraindication to, or are intolerant of other systemic therapy including cyclosporine, methotrexate or PUVA (psoralen plus ultraviolet A light).

In February 2006, REMICADE was approved in the EU for the treatment of moderately-to-severely active UC in patients who have had an inadequate response to conventional therapy, including corticosteroids and 6-MP or azathioprine, or who are intolerant to or have medical contraindications for such therapies. This approval made REMICADE the first and only biologic therapy approved to treat moderate-to-severe UC in the EU.

REMICADE is the only anti-TNF biologic therapy available as an IV form. Unlike self-administered therapies that require patients to inject themselves frequently, REMICADE is the only anti-TNF biologic administered directly by caregivers in the clinic or office setting. In RA (3 mg/kg), CD (5 mg/kg), PsA (5 mg/kg), UC (5 mg/kg), PCD (5 mg/kg), and PsO (5 mg/kg), REMICADE is a two-hour infusion administered every 8 weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6. As a result, REMICADE patients may require as few as six treatments each year. In AS (5 mg/kg), REMICADE is a two-hour infusion administered every 6 weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6.

Centocor discovered REMICADE and has exclusive marketing rights to the product in the United States.

Schering-Plough markets REMICADE in all countries outside of the United States, except in Japan and parts of the Far East where Tanabe Seiyaku, Ltd. markets the product and in China where Xian-Janssen markets REMICADE.

Important Safety Information

There are reports of serious infections, including tuberculosis (TB), sepsis and pneumonia. Some of these infections have been fatal. Tell your doctor if you have had recent or past exposure to people with TB. Your doctor will evaluate you for TB and perform a TB test. If you have latent (inactive) TB, your doctor should begin TB treatment before you start REMICADE. REMICADE can lower your ability to fight infections, so if you are prone to or have a history of infections, or develop any signs of an infection such as fever, fatigue, cough, flu or warm, red or painful skin while taking REMICADE, tell your doctor right away. Also, tell your doctor if you are scheduled to receive a vaccine or if, you have lived in a region where histoplasmosis or coccidioidomycosis is common.

Reports of a type of blood cancer called lymphoma in patients on REMICADE or other TNF blockers are rare but occur more often than expected for people in general. People who have been treated for rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, or plaque psoriasis for a long time, particularly those with highly active disease may be more prone to develop lymphoma. Cancers, other than lymphoma, have also been reported. Children and young adults who have been treated for Crohn's disease with REMICADE have developed a rare type of lymphoma that often results in death. These patients also were receiving drugs known as azathioprine or 6-mercaptopurine. If you take REMICADE or other TNF blockers, your risk for developing lymphoma or other cancers may increase. You should also tell your doctor if you have had or develop lymphoma or other cancers or if you have a lung disease called chronic obstructive pulmonary disease (COPD).

Many people with heart failure should not take REMICADE; so prior to treatment you should discuss any heart condition with your doctor. Tell your doctor right away if you develop new or worsening symptoms of heart failure (such as shortness of breath, swelling of your ankles or feet, or sudden weight gain.

Reactivation of hepatitis B virus has been reported in patients who are carriers of this virus and are taking TNF blockers, such as REMICADE. Some of these cases have been fatal. Tell your doctor if you know or think you may be a carrier of hepatitis B virus or if you experience signs of hepatitis B infection, such as feeling unwell, poor appetite, tiredness, fever, skin rash and/or joint pain.

There have been rare cases of serious liver injury in people taking REMICADE, some fatal. Tell your doctor if you have liver problems and contact your doctor immediately if you develop symptoms such as jaundice (yellow skin and eyes), dark brown urine, right-sided abdominal pain, fever, or severe fatigue.

Blood disorders have been reported, some fatal. Tell your doctor if you develop possible signs of blood disorders such as persistent fever, bruising, bleeding, or paleness while taking REMICADE. Nervous system disorders have also been reported. Tell your doctor if you have or have had a disease that affects the nervous system, or if you experience any numbness, weakness, tingling, visual disturbances or seizures while taking REMICADE.

Allergic reactions, some severe have been reported during or after infusions with REMICADE. Signs of an allergic reaction include hives, difficulty breathing, chest pain, high or low blood pressure, swelling of face and hands, and fever or chills. Tell you doctor if you have experienced a severe allergic reaction. The most common side effects of REMICADE are: respiratory infections, such as sinus infections and sore throat, headache, rash, coughing, and stomach pain.

Please read the Medication Guide for REMICADE and discuss it with your doctor.

About Centocor

Centocor is harnessing the power of world-leading research and biomanufacturing to deliver innovative biomedicines that transform patients' lives. Centocor has already brought innovation to the treatment of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, ulcerative colitis, pediatric Crohn's disease and psoriasis.

The world leader in monoclonal antibody production and technology, Centocor has brought critical biologic therapies to patients suffering from debilitating immune disorders. Centocor, Inc. is a wholly owned subsidiary of Johnson & Johnson.

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from Johnson & Johnson's expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 1, 2006. Copies of this Form 10-K, as well as subsequent filings, are available online at http://www.sec.gov or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statements as a result of new information or future events or developments.

About Schering-Plough

Schering-Plough is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough's vision is to earn the trust of the physicians, patients and customers served by its more than 32,000 people around the world. The company is based in Kenilworth, N.J., and its Web site is http://www.schering-plough.com.

SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press release contains certain "forward-looking" statements within the meaning of the Securities Reform Act of 1995, including statements related to REMICADE and the potential market for REMICADE. Forward-looking statements relate to expectations or forecasts of future events. Schering-Plough does not assume the obligation to update any forward-looking statement. Many factors could cause actual results to differ materially from Schering-Plough's forward-looking statements, including market forces, economic factors, product availability, current and future branded, generic or over-the-counter competition and the regulatory process, among other uncertainties. For further details and a discussion of risks and uncertainties that may affect forward-looking statements, see the company's Securities and Exchange Commission filings, including the company's second quarter 2006 10-Q.

References: (1) American College of Rheumatology. Who Gets Rheumatoid Arthritis? http://www.rheumatology.org/public/factsheets/ra_new.asp?aud=pat. Accessed 10/19/06. (2) Health and Quality of Life Outcomes. The Stanford Health Assessment Questionnaire: Dimensions and Practical Applications. http://www.hqlo.com/content/1/1/20. Accessed 10/20/06. (3) Landewe RB, Boers M, Verhoeven AC, et al. COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. Arthritis Rheum. 2002;46:347-356. (4) Egsmose C, Lund B, Borg G, et al. Patients with rheumatoid arthritis benefit from early 2nd line therapy: 5 year follow up of a prospective double blind placebo controlled study. J. Rheumatol. 1995;22:2208-2213. (5) American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines, 2002 Update. (6) van der Heijde DM. Joint erosions and patients with early rheumatoid arthritis. Br J Rheumatol. 1995;34(suppl 2):74-78. (7) Barrett EM, Scott DGI, Wiles NJ, Symmons DPM. The impact of rheumatoid arthritis on employment status in the early years of disease: a UK community-based study. Rheumatology. 2000;39:1403-1409. (8) Social Security Disability Insurance Program.

Web site: http://www.schering-plough.com