Rheumatoid Arthritis

A concentrated oral solution of morphine sulfate has been approved by the Food and Drug Administration, rescuing a formulation that had been slated to be taken off the market last year until physician groups spoke up about its clinical utility and lack of equivalent products.

The approval of Roxane Laboratories' product cements the FDA's decision in April 2009 to reinstate the high-concentration oral solutions of morphine sulfate to the market, but not other unapproved narcotic products for which the agency had deemed that acceptable alternatives were available.

The solution is indicated for moderate to severe, acute, and chronic pain in opioid-tolerant patients (defined as those who are taking the equivalent of 60 mg of morphine per day). It will be available in doses of 100 mg/5 mL and 20 mg/1 mL.

The FDA's decision is a part of the ongoing Unapproved Drugs Initiative that the agency began in 2006. Numerous other previously unapproved drugs, including some opioid formulations, have been approved through the initiative.

“It is a significant step toward ensuring that patients needing this medicine have access to a high-quality product,” Dr. Douglas Throckmorton, deputy director of the FDA's Center for Drug Evaluation and Research, said during the briefing.

Dr. Throckmorton added that actions that “would limit the availability of this medicine could cause unnecessary hardship to these patients and limit the treatment options available to prescribers. As such, we are working with the manufacturer of the approved product, Roxane Laboratories, to make sure that here will be enough approved drug for all patients. We will also be working with patient organizations and prescribers, so that they are both aware of this approved product.

Roxane met the FDA's standard for establishing the safety and efficacy of the oral solution by referring to the agency's prior findings for similar products. The manufacturer also gave the product a standardized drug label and a medication guide.

A concentrated oral solution of morphine sulfate has been approved by the Food and Drug Administration, rescuing a formulation that had been slated to be taken off the market last year until physician groups spoke up about its clinical utility and lack of equivalent products.

The approval of Roxane Laboratories' product cements the FDA's decision in April 2009 to reinstate the high-concentration oral solutions of morphine sulfate to the market, but not other unapproved narcotic products for which the agency had deemed that acceptable alternatives were available.

The solution is indicated for moderate to severe, acute, and chronic pain in opioid-tolerant patients (defined as those who are taking the equivalent of 60 mg of morphine per day). It will be available in doses of 100 mg/5 mL and 20 mg/1 mL.

The FDA's decision is a part of the ongoing Unapproved Drugs Initiative that the agency began in 2006. Numerous other previously unapproved drugs, including some opioid formulations, have been approved through the initiative.

“It is a significant step toward ensuring that patients needing this medicine have access to a high-quality product,” Dr. Douglas Throckmorton, deputy director of the FDA's Center for Drug Evaluation and Research, said during the briefing.

Dr. Throckmorton added that actions that “would limit the availability of this medicine could cause unnecessary hardship to these patients and limit the treatment options available to prescribers. As such, we are working with the manufacturer of the approved product, Roxane Laboratories, to make sure that here will be enough approved drug for all patients. We will also be working with patient organizations and prescribers, so that they are both aware of this approved product.

Roxane met the FDA's standard for establishing the safety and efficacy of the oral solution by referring to the agency's prior findings for similar products. The manufacturer also gave the product a standardized drug label and a medication guide.

A concentrated oral solution of morphine sulfate has been approved by the Food and Drug Administration, rescuing a formulation that had been slated to be taken off the market last year until physician groups spoke up about its clinical utility and lack of equivalent products.

The approval of Roxane Laboratories' product cements the FDA's decision in April 2009 to reinstate the high-concentration oral solutions of morphine sulfate to the market, but not other unapproved narcotic products for which the agency had deemed that acceptable alternatives were available.

The solution is indicated for moderate to severe, acute, and chronic pain in opioid-tolerant patients (defined as those who are taking the equivalent of 60 mg of morphine per day). It will be available in doses of 100 mg/5 mL and 20 mg/1 mL.

The FDA's decision is a part of the ongoing Unapproved Drugs Initiative that the agency began in 2006. Numerous other previously unapproved drugs, including some opioid formulations, have been approved through the initiative.

“It is a significant step toward ensuring that patients needing this medicine have access to a high-quality product,” Dr. Douglas Throckmorton, deputy director of the FDA's Center for Drug Evaluation and Research, said during the briefing.

Dr. Throckmorton added that actions that “would limit the availability of this medicine could cause unnecessary hardship to these patients and limit the treatment options available to prescribers. As such, we are working with the manufacturer of the approved product, Roxane Laboratories, to make sure that here will be enough approved drug for all patients. We will also be working with patient organizations and prescribers, so that they are both aware of this approved product.

Roxane met the FDA's standard for establishing the safety and efficacy of the oral solution by referring to the agency's prior findings for similar products. The manufacturer also gave the product a standardized drug label and a medication guide.

Major Finding: Experts will review new evidence to determine whether changes are needed to the OARSI guidelines for the treatment of hip and knee OA.

Data Source: An analysis of 65 systematic reviews, 266 randomized, controlled trials, and 21 economic evaluations.

Disclosures: Dr. Zhang had no financial conflicts to disclose. Several coauthors have received consulting fees, honoraria, and research support from multiple pharmaceutical and device-manufacturing companies. No potential conflict of interest was identified that would prevent any OARSI Ethics Committee members from participating in the review.

Some osteoarthritis treatments are less effective than previously thought, judging from findings from a review of research conducted since 2006.

The goal of the update of published evidence is to determine whether the current Osteoarthritis Research Society International's (OARSI) recommendations for the treatment of OA, published in 2008, need to be modified. After reviewing this update and collecting feedback, the OARSI Treatment Guidelines Committee will determine whether changes are needed in 2010.

Acetaminophen use and surgical lavage and debridement were among the therapies that may be falling out of favor to treat knee and hip OA, but evidence supporting weight reduction is on the upswing, said Dr. Weiya Zhang, a rheumatologist at the University of Nottingham (England), and colleagues.

The researchers identified 64 systematic reviews, 266 randomized controlled trials, and 21 economic evaluations related to hip and knee OA that were published between January 2006 and January 2009. “Of the 51 modalities of treatment addressed in the OARSI recommendations, 35 have now been systematically reviewed with 16 new or updated systematic reviews in the last 3 years,” the researchers wrote (Osteoarthritis Cartilage 2010 Feb. [Epub doi:10.1016/j.joca.2010.01.013]). They assessed the best available evidence for effect size (ES) with 95% confidence intervals for improving function and relieving pain and stiffness associated with OA.

The new evidence for nonpharmacologic therapies included several studies supporting weight reduction. Pooled data from two new systemic reviews showed improvements in pain (ES, 0.20) and physical function (ES, 0.23) after an average weight loss of 6.1 kg (approximately 13 pounds). The ES for pain relief for hip and knee OA were not significantly changed for acupuncture, education, exercise, and self-management. New research on electromagnetic therapy showed a relatively small improvement in function (ES, 0.33) and no significant effect on pain reduction (ES, 0.16).

The review also yielded some changes in evidence for pharmacologic OA treatments, notably acetaminophen. A review of five new studies of acetaminophen for knee OA showed no significant reductions in effect size for pain relief (pooled ES, 0.14). Other recent studies showed an increased risk of hospitalization because of perforation, peptic ulceration, and bleeding when acetaminophen doses of more than 3 g/day were used to treat OA (hazard ratio, 1.20). No data from recent studies identified significant changes in the risks and benefits of oral or topical NSAIDs, diacerhein, or interarticular corticosteroid injections for treating OA.

For surgical treatments, pooled results showed no benefit for lavage, debridement, or a combination of the two for treating OA, compared with placebo. Effect sizes for pain relief, function improvement, and stiffness reduction were 0.21, 0.11, and 0.05, respectively.

The researchers noted that there is a need for “a continuously updated, comprehensive, and coherent database of well-characterized trials of all modalities of treatment of OA.” But they emphasized that treatment guidelines must be based on the best evidence, not simply on updated cumulative evidence.

Major Finding: Experts will review new evidence to determine whether changes are needed to the OARSI guidelines for the treatment of hip and knee OA.

Data Source: An analysis of 65 systematic reviews, 266 randomized, controlled trials, and 21 economic evaluations.

Disclosures: Dr. Zhang had no financial conflicts to disclose. Several coauthors have received consulting fees, honoraria, and research support from multiple pharmaceutical and device-manufacturing companies. No potential conflict of interest was identified that would prevent any OARSI Ethics Committee members from participating in the review.

Some osteoarthritis treatments are less effective than previously thought, judging from findings from a review of research conducted since 2006.

The goal of the update of published evidence is to determine whether the current Osteoarthritis Research Society International's (OARSI) recommendations for the treatment of OA, published in 2008, need to be modified. After reviewing this update and collecting feedback, the OARSI Treatment Guidelines Committee will determine whether changes are needed in 2010.

Acetaminophen use and surgical lavage and debridement were among the therapies that may be falling out of favor to treat knee and hip OA, but evidence supporting weight reduction is on the upswing, said Dr. Weiya Zhang, a rheumatologist at the University of Nottingham (England), and colleagues.

The researchers identified 64 systematic reviews, 266 randomized controlled trials, and 21 economic evaluations related to hip and knee OA that were published between January 2006 and January 2009. “Of the 51 modalities of treatment addressed in the OARSI recommendations, 35 have now been systematically reviewed with 16 new or updated systematic reviews in the last 3 years,” the researchers wrote (Osteoarthritis Cartilage 2010 Feb. [Epub doi:10.1016/j.joca.2010.01.013]). They assessed the best available evidence for effect size (ES) with 95% confidence intervals for improving function and relieving pain and stiffness associated with OA.

The new evidence for nonpharmacologic therapies included several studies supporting weight reduction. Pooled data from two new systemic reviews showed improvements in pain (ES, 0.20) and physical function (ES, 0.23) after an average weight loss of 6.1 kg (approximately 13 pounds). The ES for pain relief for hip and knee OA were not significantly changed for acupuncture, education, exercise, and self-management. New research on electromagnetic therapy showed a relatively small improvement in function (ES, 0.33) and no significant effect on pain reduction (ES, 0.16).

The review also yielded some changes in evidence for pharmacologic OA treatments, notably acetaminophen. A review of five new studies of acetaminophen for knee OA showed no significant reductions in effect size for pain relief (pooled ES, 0.14). Other recent studies showed an increased risk of hospitalization because of perforation, peptic ulceration, and bleeding when acetaminophen doses of more than 3 g/day were used to treat OA (hazard ratio, 1.20). No data from recent studies identified significant changes in the risks and benefits of oral or topical NSAIDs, diacerhein, or interarticular corticosteroid injections for treating OA.

For surgical treatments, pooled results showed no benefit for lavage, debridement, or a combination of the two for treating OA, compared with placebo. Effect sizes for pain relief, function improvement, and stiffness reduction were 0.21, 0.11, and 0.05, respectively.

The researchers noted that there is a need for “a continuously updated, comprehensive, and coherent database of well-characterized trials of all modalities of treatment of OA.” But they emphasized that treatment guidelines must be based on the best evidence, not simply on updated cumulative evidence.

Major Finding: Experts will review new evidence to determine whether changes are needed to the OARSI guidelines for the treatment of hip and knee OA.

Data Source: An analysis of 65 systematic reviews, 266 randomized, controlled trials, and 21 economic evaluations.

Disclosures: Dr. Zhang had no financial conflicts to disclose. Several coauthors have received consulting fees, honoraria, and research support from multiple pharmaceutical and device-manufacturing companies. No potential conflict of interest was identified that would prevent any OARSI Ethics Committee members from participating in the review.

Some osteoarthritis treatments are less effective than previously thought, judging from findings from a review of research conducted since 2006.

The goal of the update of published evidence is to determine whether the current Osteoarthritis Research Society International's (OARSI) recommendations for the treatment of OA, published in 2008, need to be modified. After reviewing this update and collecting feedback, the OARSI Treatment Guidelines Committee will determine whether changes are needed in 2010.

Acetaminophen use and surgical lavage and debridement were among the therapies that may be falling out of favor to treat knee and hip OA, but evidence supporting weight reduction is on the upswing, said Dr. Weiya Zhang, a rheumatologist at the University of Nottingham (England), and colleagues.

The researchers identified 64 systematic reviews, 266 randomized controlled trials, and 21 economic evaluations related to hip and knee OA that were published between January 2006 and January 2009. “Of the 51 modalities of treatment addressed in the OARSI recommendations, 35 have now been systematically reviewed with 16 new or updated systematic reviews in the last 3 years,” the researchers wrote (Osteoarthritis Cartilage 2010 Feb. [Epub doi:10.1016/j.joca.2010.01.013]). They assessed the best available evidence for effect size (ES) with 95% confidence intervals for improving function and relieving pain and stiffness associated with OA.

The new evidence for nonpharmacologic therapies included several studies supporting weight reduction. Pooled data from two new systemic reviews showed improvements in pain (ES, 0.20) and physical function (ES, 0.23) after an average weight loss of 6.1 kg (approximately 13 pounds). The ES for pain relief for hip and knee OA were not significantly changed for acupuncture, education, exercise, and self-management. New research on electromagnetic therapy showed a relatively small improvement in function (ES, 0.33) and no significant effect on pain reduction (ES, 0.16).

The review also yielded some changes in evidence for pharmacologic OA treatments, notably acetaminophen. A review of five new studies of acetaminophen for knee OA showed no significant reductions in effect size for pain relief (pooled ES, 0.14). Other recent studies showed an increased risk of hospitalization because of perforation, peptic ulceration, and bleeding when acetaminophen doses of more than 3 g/day were used to treat OA (hazard ratio, 1.20). No data from recent studies identified significant changes in the risks and benefits of oral or topical NSAIDs, diacerhein, or interarticular corticosteroid injections for treating OA.

For surgical treatments, pooled results showed no benefit for lavage, debridement, or a combination of the two for treating OA, compared with placebo. Effect sizes for pain relief, function improvement, and stiffness reduction were 0.21, 0.11, and 0.05, respectively.

The researchers noted that there is a need for “a continuously updated, comprehensive, and coherent database of well-characterized trials of all modalities of treatment of OA.” But they emphasized that treatment guidelines must be based on the best evidence, not simply on updated cumulative evidence.

Major Finding: Early arthroscopic surgery does not have any effect beyond short-term pain relief.

Data Source: Prospective study of 20 patients with marked intraoperative chondral lesions; mean follow-up 3 years.

Disclosures: None.

Arthroscopic surgery for femoroacetabular impingement did not eliminate the need for total hip arthroplasty in 10 of 20 patients with advanced chondral lesions. The joint had to be replaced within 3 years of undergoing the less-extensive procedure.

The “discouraging” data indicate that arthroscopic surgery in patients with femoroacetabular impingement (FAI) involving more severe, generalized chondral lesions (grade II or greater on the Outerbridge scale) does not obviate the need for total hip arthroplasty (THA) or even lengthen the interval before the joint replacement procedure is required. “It seems obvious that these patients should not be treated by arthroscopic means,” reported Dr. Monika Horisberger and her associates of the University Hospital Basel (Switzerland).

They looked at 150 patients with cam and mixed FAI. Of these, “20 patients showed intraoperative marked chondral lesions of Outerbridge grade II or greater not restricted to the direct impingement zone, and were therefore included in the study,” they wrote (J. Arthro. 2010 Feb. 11 [doi:10.1016/j.arthro.2009.09.003

Preoperatively, according to the Tönnis classification, “[nine] hips had grade I osteoarthritis, [six] had grade II osteoarthritis, and [five] had grade III osteoarthritis.” The mean age was 47.3 years (range, 22-65 years) and the mean follow-up was 3.0 years (range, 1.5-4.1 years). Half of the patients were male, and one patient died of causes unrelated to the study.

Intraoperatively, all 20 patients were found to have “marked” generalized chondral damage as well as labral lesions. “Grade IV chondral lesions were localized at the impingement zone (ventral-cranial acetabulum) in 14 cases (70%) and at the corresponding femur in 3 cases (15%),” wrote the authors. “Microfracturing was performed in these areas in a total of 15 cases (75%).”

At the study's end, total hip arthroplasty had already been performed in eight patients, and two patients were scheduled to undergo the procedure after the study's conclusion. Preoperatively, three of these patients had Tönnis grade I osteoarthritis, two had grade II osteoarthritis, and five had grade III osteoarthritis. A higher preoperative Tönnis grade increased the risk for subsequent THA significantly (P = .03).

The remaining nine patients who had not undergone THA and were not planning the surgery did experience significant improvements in range of motion (internal rotation improved from 0.25 degrees preoperatively to 24.5 degrees following arthroscopy, P less than .001), flexion (from 110.8 to 125.0 degrees; P = .005) and pain on the visual analog scale (from 6.0 to 1.8; P = .002).

However, the authors said, it is unclear whether the index surgery slowed the degenerative process for the long term or whether a major part of improvement might have been because of the effect of articular debridement or therapy for labral tears rather than the correction of the causative lesion.

Dr. Horisberger conceded that the study does have weaknesses: Nevertheless, “If preoperative examinations underestimate the real extent of chondral damage found on arthroscopy, particularly if extended grade IV lesions at the femoral head are seen, THA should be recommended without further joint-preserving treatment attempts,” they asserted.

Major Finding: Early arthroscopic surgery does not have any effect beyond short-term pain relief.

Data Source: Prospective study of 20 patients with marked intraoperative chondral lesions; mean follow-up 3 years.

Disclosures: None.

Arthroscopic surgery for femoroacetabular impingement did not eliminate the need for total hip arthroplasty in 10 of 20 patients with advanced chondral lesions. The joint had to be replaced within 3 years of undergoing the less-extensive procedure.

The “discouraging” data indicate that arthroscopic surgery in patients with femoroacetabular impingement (FAI) involving more severe, generalized chondral lesions (grade II or greater on the Outerbridge scale) does not obviate the need for total hip arthroplasty (THA) or even lengthen the interval before the joint replacement procedure is required. “It seems obvious that these patients should not be treated by arthroscopic means,” reported Dr. Monika Horisberger and her associates of the University Hospital Basel (Switzerland).

They looked at 150 patients with cam and mixed FAI. Of these, “20 patients showed intraoperative marked chondral lesions of Outerbridge grade II or greater not restricted to the direct impingement zone, and were therefore included in the study,” they wrote (J. Arthro. 2010 Feb. 11 [doi:10.1016/j.arthro.2009.09.003

Preoperatively, according to the Tönnis classification, “[nine] hips had grade I osteoarthritis, [six] had grade II osteoarthritis, and [five] had grade III osteoarthritis.” The mean age was 47.3 years (range, 22-65 years) and the mean follow-up was 3.0 years (range, 1.5-4.1 years). Half of the patients were male, and one patient died of causes unrelated to the study.

Intraoperatively, all 20 patients were found to have “marked” generalized chondral damage as well as labral lesions. “Grade IV chondral lesions were localized at the impingement zone (ventral-cranial acetabulum) in 14 cases (70%) and at the corresponding femur in 3 cases (15%),” wrote the authors. “Microfracturing was performed in these areas in a total of 15 cases (75%).”

At the study's end, total hip arthroplasty had already been performed in eight patients, and two patients were scheduled to undergo the procedure after the study's conclusion. Preoperatively, three of these patients had Tönnis grade I osteoarthritis, two had grade II osteoarthritis, and five had grade III osteoarthritis. A higher preoperative Tönnis grade increased the risk for subsequent THA significantly (P = .03).

The remaining nine patients who had not undergone THA and were not planning the surgery did experience significant improvements in range of motion (internal rotation improved from 0.25 degrees preoperatively to 24.5 degrees following arthroscopy, P less than .001), flexion (from 110.8 to 125.0 degrees; P = .005) and pain on the visual analog scale (from 6.0 to 1.8; P = .002).

However, the authors said, it is unclear whether the index surgery slowed the degenerative process for the long term or whether a major part of improvement might have been because of the effect of articular debridement or therapy for labral tears rather than the correction of the causative lesion.

Dr. Horisberger conceded that the study does have weaknesses: Nevertheless, “If preoperative examinations underestimate the real extent of chondral damage found on arthroscopy, particularly if extended grade IV lesions at the femoral head are seen, THA should be recommended without further joint-preserving treatment attempts,” they asserted.

Major Finding: Early arthroscopic surgery does not have any effect beyond short-term pain relief.

Data Source: Prospective study of 20 patients with marked intraoperative chondral lesions; mean follow-up 3 years.

Disclosures: None.

Arthroscopic surgery for femoroacetabular impingement did not eliminate the need for total hip arthroplasty in 10 of 20 patients with advanced chondral lesions. The joint had to be replaced within 3 years of undergoing the less-extensive procedure.

The “discouraging” data indicate that arthroscopic surgery in patients with femoroacetabular impingement (FAI) involving more severe, generalized chondral lesions (grade II or greater on the Outerbridge scale) does not obviate the need for total hip arthroplasty (THA) or even lengthen the interval before the joint replacement procedure is required. “It seems obvious that these patients should not be treated by arthroscopic means,” reported Dr. Monika Horisberger and her associates of the University Hospital Basel (Switzerland).

They looked at 150 patients with cam and mixed FAI. Of these, “20 patients showed intraoperative marked chondral lesions of Outerbridge grade II or greater not restricted to the direct impingement zone, and were therefore included in the study,” they wrote (J. Arthro. 2010 Feb. 11 [doi:10.1016/j.arthro.2009.09.003

Preoperatively, according to the Tönnis classification, “[nine] hips had grade I osteoarthritis, [six] had grade II osteoarthritis, and [five] had grade III osteoarthritis.” The mean age was 47.3 years (range, 22-65 years) and the mean follow-up was 3.0 years (range, 1.5-4.1 years). Half of the patients were male, and one patient died of causes unrelated to the study.

Intraoperatively, all 20 patients were found to have “marked” generalized chondral damage as well as labral lesions. “Grade IV chondral lesions were localized at the impingement zone (ventral-cranial acetabulum) in 14 cases (70%) and at the corresponding femur in 3 cases (15%),” wrote the authors. “Microfracturing was performed in these areas in a total of 15 cases (75%).”

At the study's end, total hip arthroplasty had already been performed in eight patients, and two patients were scheduled to undergo the procedure after the study's conclusion. Preoperatively, three of these patients had Tönnis grade I osteoarthritis, two had grade II osteoarthritis, and five had grade III osteoarthritis. A higher preoperative Tönnis grade increased the risk for subsequent THA significantly (P = .03).

The remaining nine patients who had not undergone THA and were not planning the surgery did experience significant improvements in range of motion (internal rotation improved from 0.25 degrees preoperatively to 24.5 degrees following arthroscopy, P less than .001), flexion (from 110.8 to 125.0 degrees; P = .005) and pain on the visual analog scale (from 6.0 to 1.8; P = .002).

However, the authors said, it is unclear whether the index surgery slowed the degenerative process for the long term or whether a major part of improvement might have been because of the effect of articular debridement or therapy for labral tears rather than the correction of the causative lesion.

Dr. Horisberger conceded that the study does have weaknesses: Nevertheless, “If preoperative examinations underestimate the real extent of chondral damage found on arthroscopy, particularly if extended grade IV lesions at the femoral head are seen, THA should be recommended without further joint-preserving treatment attempts,” they asserted.

Major Finding: Response rate to rituximab is highest in RA patients with elevated CRP and RF positivity.

Data Source: Post hoc analysis of data from REFLEX and SERENE trials.

Disclosures: The study was supported by Genentech Inc., F. Hoffmann-LaRoche Ltd., and Biogen Idec Inc. Dr. Faraawi reported receiving research grants from Roche, Pfizer Inc., UCB, Schering-Plough Corp., and Wyeth.

QUEBEC CITY — Baseline serologic biomarkers offer rheumatologists the possibility of tailoring rheumatoid arthritis medications to fit various subgroups of patients, thereby increasing the likelihood of achieving a good response to treatment, said Dr. Rafat Faraawi at the annual meeting of the Canadian Rheumatology Association.

In a sea of pharmaceuticals for RA, with no clear understanding of why some patients respond to one agent and not to another, biomarkers are a potential tool for predicting treatment response, Dr. Faraawi said in an interview with

“We still don't have guidelines on how to select pharmaceuticals. More or less, [the drugs] all have the same efficacy. There are minor differences, and then the selection depends on many factors.

“We depend on personal preference, physician experience, certain peculiarities of the drugs, mechanism of action,” according to Dr. Faraawi.

In a post hoc analysis of two large trials of rituximab, his group discovered that a subgroup of patients with high serum levels of C-reactive protein (CRP) as well as seropositivity for rheumatoid factor (RF) had the highest response to rituximab. “If you want to select patients who will get a response to this expensive biologic, then those with positive rheumatoid factor and an elevated C-reactive protein most likely will show a better response than [will] seronegative patients or those with low CRP.

“And if they have a combination of both, that is even better,” said Dr. Faraawi, who is a rheumatologist at McMaster University in Kitchener, Ont.

He presented the data as a poster at the meeting.

The investigators used data from REFLEX (Randomized Evaluation of Long-Term Efficacy of Rituximab in RA) and SERENE (Study Evaluating Rituximab's Efficacy in Methotrexate Inadequate Responders).

Both are randomized, placebo-controlled trials of rituximab in patients with inadequate response to either tumor necrosis factor inhibitors or methotrexate, respectively (Arthritis Rheum. 2006;54:2793-806; ACR 2008, abstract 364).

Both trials reported ACR 50 response rates for rituximab, compared with placebo, after 24 weeks.

The REFLEX trial (n = 517) showed an ACR 50 response of 27% in the treated group, compared with 5% in placebo. And the SERENE trial (n = 501) showed an ACR 50 response of 26% in the treated group, compared with 9% in placebo.

For both trials, baseline levels of 19 serologic markers and 9 clinical features were recorded.

After an analysis of baseline and outcome data from both trials, Dr. Faraawi's study identified four serologic biomarkers—RF, CRP, IgG anti–cyclic citrullinated peptide 3 (CCP3) antibodies, and soluble cluster of differentiation 25 (CD25)—that were predictive of response to rituximab, he explained.

Of these, seropositivity for RF and CRP were the most predictive, and this was further enhanced when both biomarkers were presented.

For example, in the REFLEX trial, the overall ACR 50 response rate was 27% in the treated group, whereas the subgroup of patients with CRP levels above 2.9 mg/dL and positive RF of any isotope (defined as IgA RF greater than 25 U/mL, IgG RF greater than 20 U/mL, IgM RF greater than 20 U/mL, total RF greater than 20 IU/mL) had an ACR 50 response rate of 31% (placebo, 1%).

Similarly, in the SERENE trial, the overall ACR 50 response rate was 26% in the treated group, whereas the response rate was 39% in the same subgroup of patients who were positive for RF and had an elevated CRP (placebo, 7%).

Rituximab is a monoclonal antibody that selectively targets CD20-positive B cells, which secrete rheumatoid factor, said Dr. Faraawi.

“That is why, for this particular drug, patients with positive rheumatoid factor respond well. That doesn't mean this agent does not work for patients with low markers. It still works. But the likelihood of response is greater with positive markers.”

He said that large trials are needed to further clarify which markers can help in the selection of agents for specific patients.

Major Finding: Response rate to rituximab is highest in RA patients with elevated CRP and RF positivity.

Data Source: Post hoc analysis of data from REFLEX and SERENE trials.

Disclosures: The study was supported by Genentech Inc., F. Hoffmann-LaRoche Ltd., and Biogen Idec Inc. Dr. Faraawi reported receiving research grants from Roche, Pfizer Inc., UCB, Schering-Plough Corp., and Wyeth.

QUEBEC CITY — Baseline serologic biomarkers offer rheumatologists the possibility of tailoring rheumatoid arthritis medications to fit various subgroups of patients, thereby increasing the likelihood of achieving a good response to treatment, said Dr. Rafat Faraawi at the annual meeting of the Canadian Rheumatology Association.

In a sea of pharmaceuticals for RA, with no clear understanding of why some patients respond to one agent and not to another, biomarkers are a potential tool for predicting treatment response, Dr. Faraawi said in an interview with

“We still don't have guidelines on how to select pharmaceuticals. More or less, [the drugs] all have the same efficacy. There are minor differences, and then the selection depends on many factors.

“We depend on personal preference, physician experience, certain peculiarities of the drugs, mechanism of action,” according to Dr. Faraawi.

In a post hoc analysis of two large trials of rituximab, his group discovered that a subgroup of patients with high serum levels of C-reactive protein (CRP) as well as seropositivity for rheumatoid factor (RF) had the highest response to rituximab. “If you want to select patients who will get a response to this expensive biologic, then those with positive rheumatoid factor and an elevated C-reactive protein most likely will show a better response than [will] seronegative patients or those with low CRP.

“And if they have a combination of both, that is even better,” said Dr. Faraawi, who is a rheumatologist at McMaster University in Kitchener, Ont.

He presented the data as a poster at the meeting.

The investigators used data from REFLEX (Randomized Evaluation of Long-Term Efficacy of Rituximab in RA) and SERENE (Study Evaluating Rituximab's Efficacy in Methotrexate Inadequate Responders).

Both are randomized, placebo-controlled trials of rituximab in patients with inadequate response to either tumor necrosis factor inhibitors or methotrexate, respectively (Arthritis Rheum. 2006;54:2793-806; ACR 2008, abstract 364).

Both trials reported ACR 50 response rates for rituximab, compared with placebo, after 24 weeks.

The REFLEX trial (n = 517) showed an ACR 50 response of 27% in the treated group, compared with 5% in placebo. And the SERENE trial (n = 501) showed an ACR 50 response of 26% in the treated group, compared with 9% in placebo.

For both trials, baseline levels of 19 serologic markers and 9 clinical features were recorded.

After an analysis of baseline and outcome data from both trials, Dr. Faraawi's study identified four serologic biomarkers—RF, CRP, IgG anti–cyclic citrullinated peptide 3 (CCP3) antibodies, and soluble cluster of differentiation 25 (CD25)—that were predictive of response to rituximab, he explained.

Of these, seropositivity for RF and CRP were the most predictive, and this was further enhanced when both biomarkers were presented.

For example, in the REFLEX trial, the overall ACR 50 response rate was 27% in the treated group, whereas the subgroup of patients with CRP levels above 2.9 mg/dL and positive RF of any isotope (defined as IgA RF greater than 25 U/mL, IgG RF greater than 20 U/mL, IgM RF greater than 20 U/mL, total RF greater than 20 IU/mL) had an ACR 50 response rate of 31% (placebo, 1%).

Similarly, in the SERENE trial, the overall ACR 50 response rate was 26% in the treated group, whereas the response rate was 39% in the same subgroup of patients who were positive for RF and had an elevated CRP (placebo, 7%).

Rituximab is a monoclonal antibody that selectively targets CD20-positive B cells, which secrete rheumatoid factor, said Dr. Faraawi.

“That is why, for this particular drug, patients with positive rheumatoid factor respond well. That doesn't mean this agent does not work for patients with low markers. It still works. But the likelihood of response is greater with positive markers.”

He said that large trials are needed to further clarify which markers can help in the selection of agents for specific patients.

Major Finding: Response rate to rituximab is highest in RA patients with elevated CRP and RF positivity.

Data Source: Post hoc analysis of data from REFLEX and SERENE trials.

Disclosures: The study was supported by Genentech Inc., F. Hoffmann-LaRoche Ltd., and Biogen Idec Inc. Dr. Faraawi reported receiving research grants from Roche, Pfizer Inc., UCB, Schering-Plough Corp., and Wyeth.

QUEBEC CITY — Baseline serologic biomarkers offer rheumatologists the possibility of tailoring rheumatoid arthritis medications to fit various subgroups of patients, thereby increasing the likelihood of achieving a good response to treatment, said Dr. Rafat Faraawi at the annual meeting of the Canadian Rheumatology Association.

In a sea of pharmaceuticals for RA, with no clear understanding of why some patients respond to one agent and not to another, biomarkers are a potential tool for predicting treatment response, Dr. Faraawi said in an interview with

“We still don't have guidelines on how to select pharmaceuticals. More or less, [the drugs] all have the same efficacy. There are minor differences, and then the selection depends on many factors.

“We depend on personal preference, physician experience, certain peculiarities of the drugs, mechanism of action,” according to Dr. Faraawi.

In a post hoc analysis of two large trials of rituximab, his group discovered that a subgroup of patients with high serum levels of C-reactive protein (CRP) as well as seropositivity for rheumatoid factor (RF) had the highest response to rituximab. “If you want to select patients who will get a response to this expensive biologic, then those with positive rheumatoid factor and an elevated C-reactive protein most likely will show a better response than [will] seronegative patients or those with low CRP.

“And if they have a combination of both, that is even better,” said Dr. Faraawi, who is a rheumatologist at McMaster University in Kitchener, Ont.

He presented the data as a poster at the meeting.

The investigators used data from REFLEX (Randomized Evaluation of Long-Term Efficacy of Rituximab in RA) and SERENE (Study Evaluating Rituximab's Efficacy in Methotrexate Inadequate Responders).

Both are randomized, placebo-controlled trials of rituximab in patients with inadequate response to either tumor necrosis factor inhibitors or methotrexate, respectively (Arthritis Rheum. 2006;54:2793-806; ACR 2008, abstract 364).

Both trials reported ACR 50 response rates for rituximab, compared with placebo, after 24 weeks.

The REFLEX trial (n = 517) showed an ACR 50 response of 27% in the treated group, compared with 5% in placebo. And the SERENE trial (n = 501) showed an ACR 50 response of 26% in the treated group, compared with 9% in placebo.

For both trials, baseline levels of 19 serologic markers and 9 clinical features were recorded.

After an analysis of baseline and outcome data from both trials, Dr. Faraawi's study identified four serologic biomarkers—RF, CRP, IgG anti–cyclic citrullinated peptide 3 (CCP3) antibodies, and soluble cluster of differentiation 25 (CD25)—that were predictive of response to rituximab, he explained.

Of these, seropositivity for RF and CRP were the most predictive, and this was further enhanced when both biomarkers were presented.

For example, in the REFLEX trial, the overall ACR 50 response rate was 27% in the treated group, whereas the subgroup of patients with CRP levels above 2.9 mg/dL and positive RF of any isotope (defined as IgA RF greater than 25 U/mL, IgG RF greater than 20 U/mL, IgM RF greater than 20 U/mL, total RF greater than 20 IU/mL) had an ACR 50 response rate of 31% (placebo, 1%).

Similarly, in the SERENE trial, the overall ACR 50 response rate was 26% in the treated group, whereas the response rate was 39% in the same subgroup of patients who were positive for RF and had an elevated CRP (placebo, 7%).

Rituximab is a monoclonal antibody that selectively targets CD20-positive B cells, which secrete rheumatoid factor, said Dr. Faraawi.

“That is why, for this particular drug, patients with positive rheumatoid factor respond well. That doesn't mean this agent does not work for patients with low markers. It still works. But the likelihood of response is greater with positive markers.”

He said that large trials are needed to further clarify which markers can help in the selection of agents for specific patients.

QUEBEC CITY — The increased rate of serious infections seen in patients with rheumatoid arthritis is most strongly associated with current glucocorticoid exposure, but comorbidities are also an important factor, according to findings from a large, nested, case-control study presented at the annual meeting of the Canadian Rheumatology Association.

“When we try to predict risk of infection, we tend to focus on the drugs, particularly the immunosuppressive agents,” said principal investigator Dr. Claire Bombardier in an interview. The findings from this research show that rheumatologists need to pay more attention to other, heretofore largely overlooked risk factors, she added.

Dr. Bombardier noted her study's serious flaw: It relies on data from a source that does not include complete information on exposure to biologic agents. Use of biologics has been linked to an increased risk for reactivation of tuberculosis as well as primary fungal and other infections.

In two separate posters, Dr. Bombardier presented a retrospective examination of serious infections requiring hospitalization, as well as serious fungal infections, in a cohort of 81,497 seniors with RA.

All subjects were aged older than 65 years (mean, 69 years), and were drawn from the Ontario Biologics Research Initiative administrative database, said Dr. Bombardier, professor of medicine and director of the division of rheumatology at the University of Toronto.

The first study involved a total of 14,214 subjects with serious infection requiring hospitalization in 1992-2006, with the most common infection being pneumonia (n = 7,026). These subjects were matched to controls from the same cohort according to age, sex, and year of cohort entry. Multivariate logistic regression analysis was used to assess the independent effects of demographics (age, income, rural/urban residence); comorbidity (based on the Charlson-Deyo comorbidity index); markers of RA severity (number of rheumatology visits, history of joint replacement, presence of extra-articular RA, and prescription NSAID use); and RA-related drug exposure. Past and current drug exposures were determined based on electronic provincial prescription data, although most biologic use was probably not captured in this database because it is not covered by provincial health insurance.

After adjustment, the study found that current use of glucocorticoids was associated with the highest risk of infection, and that this risk increased with increasing doses. Compared with no exposure, a glucocorticoid dose of 5 mg or less per day was associated with an odds ratio of infection of 3.81. At 6-9 mg/day, the OR was 4.56, rising to 5.58 at a dose of 10-19 mg/day, and the OR was 5.46 at a dose of 20 mg or more per day.

But other drugs—both biologics (to the extent their effect was assessed) and disease-modifying antirheumatic drugs—were also associated with risk, although less so, with ORs ranging from 1.1 to 3.64, said Dr. Bombardier. Within the context of these nonglucocorticoid drugs, comorbidity and markers of disease severity were associated with a similar range of risks of infection. Chronic lung disease was associated with an OR of 1.47, and renal disease with OR of 1.38. The Charlson-Deyo comorbidity index score of 1 had an OR of 1.44, whereas a score of 2 or more had an OR of 1.59.

In terms of markers of disease activity, the presence of one or more extra-articular feature of RA was associated with an OR of 1.14, and a history of joint replacement with an OR of 1.05.

Dr. Bombardier's second study focused specifically on the risk of serious fungal infections within the same cohort, because of “the flurry of interest in fungal infections recently,” she said.

A total of 53 serious fungal infections occurred within the cohort, including aspergillosis, coccidioidomycosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, and systemic candidiasis. As with the previous study, cases of infection were matched to 265 controls from the same cohort.

Again, univariate and multivariate logistic regression analysis assessed the independent effects of demographics, comorbidity, markers of RA severity, and RA-related drug exposure.

After adjustment, the study found that cases were more likely than controls to live in rural areas (OR, 6.8) and to have more comorbidity, most commonly lung (OR, 1.27) and renal disease (OR, 1.95).

Compared with no prednisone, there was a greater risk of fungal infection associated with prednisone doses of 10-19 mg/day (OR, 1.90) and more than 20 mg/day (OR, 4.0).

Only 17 of 53 cases were currently exposed to a DMARD at the time of the fungal infection, and no case was currently exposed to a biologic agent.

Compared with no exposure, a higher risk of infection was associated with current exposure to sulfasalazine (OR, 1.90), methotrexate (OR, 1.66), and hydroxychloroquine (OR, 1.64).

Dr. Bombardier said this information should help physicians refine decision making about adjusting RA patients' medication dose.

“When you're worrying about a patient, don't focus just on the drugs. Think about whether they have renal disease, or whether they have lung disease. That is as important [as], if not more important than, worrying about the drugs,” she said.

Disclosures: Funding for the study was provided by the Canadian Institute of Health Research and the Ontario Ministry of Health and Long-Term Care. Dr. Bombardier holds a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care.

QUEBEC CITY — The increased rate of serious infections seen in patients with rheumatoid arthritis is most strongly associated with current glucocorticoid exposure, but comorbidities are also an important factor, according to findings from a large, nested, case-control study presented at the annual meeting of the Canadian Rheumatology Association.

“When we try to predict risk of infection, we tend to focus on the drugs, particularly the immunosuppressive agents,” said principal investigator Dr. Claire Bombardier in an interview. The findings from this research show that rheumatologists need to pay more attention to other, heretofore largely overlooked risk factors, she added.

Dr. Bombardier noted her study's serious flaw: It relies on data from a source that does not include complete information on exposure to biologic agents. Use of biologics has been linked to an increased risk for reactivation of tuberculosis as well as primary fungal and other infections.

In two separate posters, Dr. Bombardier presented a retrospective examination of serious infections requiring hospitalization, as well as serious fungal infections, in a cohort of 81,497 seniors with RA.

All subjects were aged older than 65 years (mean, 69 years), and were drawn from the Ontario Biologics Research Initiative administrative database, said Dr. Bombardier, professor of medicine and director of the division of rheumatology at the University of Toronto.

The first study involved a total of 14,214 subjects with serious infection requiring hospitalization in 1992-2006, with the most common infection being pneumonia (n = 7,026). These subjects were matched to controls from the same cohort according to age, sex, and year of cohort entry. Multivariate logistic regression analysis was used to assess the independent effects of demographics (age, income, rural/urban residence); comorbidity (based on the Charlson-Deyo comorbidity index); markers of RA severity (number of rheumatology visits, history of joint replacement, presence of extra-articular RA, and prescription NSAID use); and RA-related drug exposure. Past and current drug exposures were determined based on electronic provincial prescription data, although most biologic use was probably not captured in this database because it is not covered by provincial health insurance.

After adjustment, the study found that current use of glucocorticoids was associated with the highest risk of infection, and that this risk increased with increasing doses. Compared with no exposure, a glucocorticoid dose of 5 mg or less per day was associated with an odds ratio of infection of 3.81. At 6-9 mg/day, the OR was 4.56, rising to 5.58 at a dose of 10-19 mg/day, and the OR was 5.46 at a dose of 20 mg or more per day.

But other drugs—both biologics (to the extent their effect was assessed) and disease-modifying antirheumatic drugs—were also associated with risk, although less so, with ORs ranging from 1.1 to 3.64, said Dr. Bombardier. Within the context of these nonglucocorticoid drugs, comorbidity and markers of disease severity were associated with a similar range of risks of infection. Chronic lung disease was associated with an OR of 1.47, and renal disease with OR of 1.38. The Charlson-Deyo comorbidity index score of 1 had an OR of 1.44, whereas a score of 2 or more had an OR of 1.59.

In terms of markers of disease activity, the presence of one or more extra-articular feature of RA was associated with an OR of 1.14, and a history of joint replacement with an OR of 1.05.

Dr. Bombardier's second study focused specifically on the risk of serious fungal infections within the same cohort, because of “the flurry of interest in fungal infections recently,” she said.

A total of 53 serious fungal infections occurred within the cohort, including aspergillosis, coccidioidomycosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, and systemic candidiasis. As with the previous study, cases of infection were matched to 265 controls from the same cohort.

Again, univariate and multivariate logistic regression analysis assessed the independent effects of demographics, comorbidity, markers of RA severity, and RA-related drug exposure.

After adjustment, the study found that cases were more likely than controls to live in rural areas (OR, 6.8) and to have more comorbidity, most commonly lung (OR, 1.27) and renal disease (OR, 1.95).

Compared with no prednisone, there was a greater risk of fungal infection associated with prednisone doses of 10-19 mg/day (OR, 1.90) and more than 20 mg/day (OR, 4.0).

Only 17 of 53 cases were currently exposed to a DMARD at the time of the fungal infection, and no case was currently exposed to a biologic agent.

Compared with no exposure, a higher risk of infection was associated with current exposure to sulfasalazine (OR, 1.90), methotrexate (OR, 1.66), and hydroxychloroquine (OR, 1.64).

Dr. Bombardier said this information should help physicians refine decision making about adjusting RA patients' medication dose.

“When you're worrying about a patient, don't focus just on the drugs. Think about whether they have renal disease, or whether they have lung disease. That is as important [as], if not more important than, worrying about the drugs,” she said.

Disclosures: Funding for the study was provided by the Canadian Institute of Health Research and the Ontario Ministry of Health and Long-Term Care. Dr. Bombardier holds a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care.

QUEBEC CITY — The increased rate of serious infections seen in patients with rheumatoid arthritis is most strongly associated with current glucocorticoid exposure, but comorbidities are also an important factor, according to findings from a large, nested, case-control study presented at the annual meeting of the Canadian Rheumatology Association.

“When we try to predict risk of infection, we tend to focus on the drugs, particularly the immunosuppressive agents,” said principal investigator Dr. Claire Bombardier in an interview. The findings from this research show that rheumatologists need to pay more attention to other, heretofore largely overlooked risk factors, she added.

Dr. Bombardier noted her study's serious flaw: It relies on data from a source that does not include complete information on exposure to biologic agents. Use of biologics has been linked to an increased risk for reactivation of tuberculosis as well as primary fungal and other infections.

In two separate posters, Dr. Bombardier presented a retrospective examination of serious infections requiring hospitalization, as well as serious fungal infections, in a cohort of 81,497 seniors with RA.

All subjects were aged older than 65 years (mean, 69 years), and were drawn from the Ontario Biologics Research Initiative administrative database, said Dr. Bombardier, professor of medicine and director of the division of rheumatology at the University of Toronto.

The first study involved a total of 14,214 subjects with serious infection requiring hospitalization in 1992-2006, with the most common infection being pneumonia (n = 7,026). These subjects were matched to controls from the same cohort according to age, sex, and year of cohort entry. Multivariate logistic regression analysis was used to assess the independent effects of demographics (age, income, rural/urban residence); comorbidity (based on the Charlson-Deyo comorbidity index); markers of RA severity (number of rheumatology visits, history of joint replacement, presence of extra-articular RA, and prescription NSAID use); and RA-related drug exposure. Past and current drug exposures were determined based on electronic provincial prescription data, although most biologic use was probably not captured in this database because it is not covered by provincial health insurance.

After adjustment, the study found that current use of glucocorticoids was associated with the highest risk of infection, and that this risk increased with increasing doses. Compared with no exposure, a glucocorticoid dose of 5 mg or less per day was associated with an odds ratio of infection of 3.81. At 6-9 mg/day, the OR was 4.56, rising to 5.58 at a dose of 10-19 mg/day, and the OR was 5.46 at a dose of 20 mg or more per day.

But other drugs—both biologics (to the extent their effect was assessed) and disease-modifying antirheumatic drugs—were also associated with risk, although less so, with ORs ranging from 1.1 to 3.64, said Dr. Bombardier. Within the context of these nonglucocorticoid drugs, comorbidity and markers of disease severity were associated with a similar range of risks of infection. Chronic lung disease was associated with an OR of 1.47, and renal disease with OR of 1.38. The Charlson-Deyo comorbidity index score of 1 had an OR of 1.44, whereas a score of 2 or more had an OR of 1.59.

In terms of markers of disease activity, the presence of one or more extra-articular feature of RA was associated with an OR of 1.14, and a history of joint replacement with an OR of 1.05.

Dr. Bombardier's second study focused specifically on the risk of serious fungal infections within the same cohort, because of “the flurry of interest in fungal infections recently,” she said.

A total of 53 serious fungal infections occurred within the cohort, including aspergillosis, coccidioidomycosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, and systemic candidiasis. As with the previous study, cases of infection were matched to 265 controls from the same cohort.

Again, univariate and multivariate logistic regression analysis assessed the independent effects of demographics, comorbidity, markers of RA severity, and RA-related drug exposure.

After adjustment, the study found that cases were more likely than controls to live in rural areas (OR, 6.8) and to have more comorbidity, most commonly lung (OR, 1.27) and renal disease (OR, 1.95).

Compared with no prednisone, there was a greater risk of fungal infection associated with prednisone doses of 10-19 mg/day (OR, 1.90) and more than 20 mg/day (OR, 4.0).

Only 17 of 53 cases were currently exposed to a DMARD at the time of the fungal infection, and no case was currently exposed to a biologic agent.

Compared with no exposure, a higher risk of infection was associated with current exposure to sulfasalazine (OR, 1.90), methotrexate (OR, 1.66), and hydroxychloroquine (OR, 1.64).

Dr. Bombardier said this information should help physicians refine decision making about adjusting RA patients' medication dose.

“When you're worrying about a patient, don't focus just on the drugs. Think about whether they have renal disease, or whether they have lung disease. That is as important [as], if not more important than, worrying about the drugs,” she said.

Disclosures: Funding for the study was provided by the Canadian Institute of Health Research and the Ontario Ministry of Health and Long-Term Care. Dr. Bombardier holds a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care.

Treatment response and disease remission rates were lowest with infliximab and highest with adalimumab in a large Danish cohort analysis of patients who were treated for rheumatoid arthritis with tumor necrosis factor–alpha inhibitors, judging from recent findings.

Data from the DANBIO (Dansk Reumatologisk Database) registry also revealed that TNF-alpha adherence was lowest with infliximab and highest with etanercept, and that older age, low functional status, and concomitant prednisolone treatment were negative predictors of clinical response and remission, according to Dr. Merete Lund Hetland of Copenhagen University and her associates.

The DANBIO registry has monitored and reported details of TNF-alpha inhibitor therapy for RA patients since October 2000.

Sponsored by Danish hospital owners and the pharmaceutical companies that offer biologic treatments for rheumatologic disease (Abbott, Wyeth, Schering-Plough, Bristol-Myers Squibb, Roche, and UCB-Nordic), DANBIO is approved by the Danish National Board of Health as a national quality registry, Dr. Hetland and her associates wrote (Arthritis Rheum. 2010;62:22-32).

This study is believed to be the first direct comparison between adalimumab, etanercept, and infliximab and the ability of the three agents to elicit treatment goals including remission, they noted.

All patients included in the study had RA and had been treated with one or more conventional disease-modifying antirheumatic drugs (DMARDs), but those treatments had failed, and one of the three biologic agents was initiated. Concomitant methotrexate or other DMARD and prednisolone were administered based on the decision of the treating rheumatologist.

The initial study population comprised 2,326 patients, of whom 449 withdrew prior to the first 6 months of the study. Of those 449, 52% withdrew because of lack of efficacy and 38% from adverse events.

Among the 1,877 patients who had not withdrawn, an ACR 70 (American College of Rheumatology 70) response was achieved after 6 months in 19% of them (Arthritis Rheum. 1995;38:727-35), a good response by the EULAR (European League Against Rheumatism) criteria in 41% of them (Arthritis Rheum. 1996;39:34-40), remission by DAS28 (Disease Activity Score in 28 joints) in 25% of them, and CDAI (Clinical Disease Activity Index) remission in 13%.

Older age, low functional status as reflected in a high score on the Health Assessment Questionnaire, and concomitant prednisolone treatment were negative predictors of an ACR 70 response, whereas concomitant methotrexate, male sex, number of previous DMARD treatments, and disease duration were not predictors.

The patterns were similar for all outcome measures at 6 and 12 months, according to Dr. Hetland and her associates.

Overall, the crude treatment response rates after 6 and 12 months were highest for adalimumab (544 patients), intermediate for etanercept (425), and poorest for infliximab (908).

After correction for withdrawals from the study, ACR 70 was achieved at 6 months by 19% of those receiving adalimumab, by 17% of those using etanercept, and by 11% of those on infliximab. A good EULAR response was reported at 6 months in 41%, 34%, and 27%, respectively.

Similarly, DAS28 remission at 6 months occurred in 26% with adalimumab, 21% with etanercept, and 17% with infliximab; CDAI remission occurred in 15%, 10%, and 8%, respectively.

Combination therapy with methotrexate and prednisolone was used more often by those taking infliximab than by those using the other two TNF-alpha inhibitors.

After adjustment for that, as well as previous DMARD use, sex, age, disease duration, seropositivity, and baseline functional status, the odds ratios for achieving an ACR 70 response after 6 months of treatment were 2.05 for adalimumab and 1.78 for etanercept, compared with infliximab.

Adalimumab and etanercept were not significantly different, the investigators reported.

The odds ratios for adalimumab vs. infliximab were statistically significant for all outcome measures, ranging from 1.78 to 2.76. For etanercept vs. infliximab, odds ratios ranged from 1.16 to 1.99, which were statistically significant for ACR 70 and EULAR response measures, but not for the two remission outcomes.

Adalimumab produced a significantly higher EULAR good response (OR, 1.49) and CDAI remission (OR, 1.58) than did etanercept.

Drug adherence was highest for etanercept and lowest for infliximab. At 48 months, unadjusted adherence rates were 52% for adalimumab, 56% for etanercept, and 41% for infliximab, Dr. Hetland and her associates said.

Disclosures: This study was supported by unrestricted grants to DANBIO from its participating companies, which had no role in the study design, nor the collection, analysis, or interpretation of the data or the decision to submit the manuscript for publication.

Dr. Hetland's work on this study was supported by a grant from the Danish Rheumatism Association and a private foundation.

She has received consulting fees, speaking fees, and/or research grants of less than $10,000 each from all of the companies (except Bristol-Myers Squibb) that were involved in DANBIO, and grants of more than $10,000 each from all the participating companies on behalf of DANBIO.

Several of the 14 other coauthors have similar disclosures.

Treatment response and disease remission rates were lowest with infliximab and highest with adalimumab in a large Danish cohort analysis of patients who were treated for rheumatoid arthritis with tumor necrosis factor–alpha inhibitors, judging from recent findings.

Data from the DANBIO (Dansk Reumatologisk Database) registry also revealed that TNF-alpha adherence was lowest with infliximab and highest with etanercept, and that older age, low functional status, and concomitant prednisolone treatment were negative predictors of clinical response and remission, according to Dr. Merete Lund Hetland of Copenhagen University and her associates.

The DANBIO registry has monitored and reported details of TNF-alpha inhibitor therapy for RA patients since October 2000.

Sponsored by Danish hospital owners and the pharmaceutical companies that offer biologic treatments for rheumatologic disease (Abbott, Wyeth, Schering-Plough, Bristol-Myers Squibb, Roche, and UCB-Nordic), DANBIO is approved by the Danish National Board of Health as a national quality registry, Dr. Hetland and her associates wrote (Arthritis Rheum. 2010;62:22-32).

This study is believed to be the first direct comparison between adalimumab, etanercept, and infliximab and the ability of the three agents to elicit treatment goals including remission, they noted.

All patients included in the study had RA and had been treated with one or more conventional disease-modifying antirheumatic drugs (DMARDs), but those treatments had failed, and one of the three biologic agents was initiated. Concomitant methotrexate or other DMARD and prednisolone were administered based on the decision of the treating rheumatologist.

The initial study population comprised 2,326 patients, of whom 449 withdrew prior to the first 6 months of the study. Of those 449, 52% withdrew because of lack of efficacy and 38% from adverse events.

Among the 1,877 patients who had not withdrawn, an ACR 70 (American College of Rheumatology 70) response was achieved after 6 months in 19% of them (Arthritis Rheum. 1995;38:727-35), a good response by the EULAR (European League Against Rheumatism) criteria in 41% of them (Arthritis Rheum. 1996;39:34-40), remission by DAS28 (Disease Activity Score in 28 joints) in 25% of them, and CDAI (Clinical Disease Activity Index) remission in 13%.

Older age, low functional status as reflected in a high score on the Health Assessment Questionnaire, and concomitant prednisolone treatment were negative predictors of an ACR 70 response, whereas concomitant methotrexate, male sex, number of previous DMARD treatments, and disease duration were not predictors.

The patterns were similar for all outcome measures at 6 and 12 months, according to Dr. Hetland and her associates.

Overall, the crude treatment response rates after 6 and 12 months were highest for adalimumab (544 patients), intermediate for etanercept (425), and poorest for infliximab (908).

After correction for withdrawals from the study, ACR 70 was achieved at 6 months by 19% of those receiving adalimumab, by 17% of those using etanercept, and by 11% of those on infliximab. A good EULAR response was reported at 6 months in 41%, 34%, and 27%, respectively.

Similarly, DAS28 remission at 6 months occurred in 26% with adalimumab, 21% with etanercept, and 17% with infliximab; CDAI remission occurred in 15%, 10%, and 8%, respectively.

Combination therapy with methotrexate and prednisolone was used more often by those taking infliximab than by those using the other two TNF-alpha inhibitors.

After adjustment for that, as well as previous DMARD use, sex, age, disease duration, seropositivity, and baseline functional status, the odds ratios for achieving an ACR 70 response after 6 months of treatment were 2.05 for adalimumab and 1.78 for etanercept, compared with infliximab.

Adalimumab and etanercept were not significantly different, the investigators reported.

The odds ratios for adalimumab vs. infliximab were statistically significant for all outcome measures, ranging from 1.78 to 2.76. For etanercept vs. infliximab, odds ratios ranged from 1.16 to 1.99, which were statistically significant for ACR 70 and EULAR response measures, but not for the two remission outcomes.

Adalimumab produced a significantly higher EULAR good response (OR, 1.49) and CDAI remission (OR, 1.58) than did etanercept.

Drug adherence was highest for etanercept and lowest for infliximab. At 48 months, unadjusted adherence rates were 52% for adalimumab, 56% for etanercept, and 41% for infliximab, Dr. Hetland and her associates said.

Disclosures: This study was supported by unrestricted grants to DANBIO from its participating companies, which had no role in the study design, nor the collection, analysis, or interpretation of the data or the decision to submit the manuscript for publication.

Dr. Hetland's work on this study was supported by a grant from the Danish Rheumatism Association and a private foundation.

She has received consulting fees, speaking fees, and/or research grants of less than $10,000 each from all of the companies (except Bristol-Myers Squibb) that were involved in DANBIO, and grants of more than $10,000 each from all the participating companies on behalf of DANBIO.

Several of the 14 other coauthors have similar disclosures.

Treatment response and disease remission rates were lowest with infliximab and highest with adalimumab in a large Danish cohort analysis of patients who were treated for rheumatoid arthritis with tumor necrosis factor–alpha inhibitors, judging from recent findings.

Data from the DANBIO (Dansk Reumatologisk Database) registry also revealed that TNF-alpha adherence was lowest with infliximab and highest with etanercept, and that older age, low functional status, and concomitant prednisolone treatment were negative predictors of clinical response and remission, according to Dr. Merete Lund Hetland of Copenhagen University and her associates.

The DANBIO registry has monitored and reported details of TNF-alpha inhibitor therapy for RA patients since October 2000.

Sponsored by Danish hospital owners and the pharmaceutical companies that offer biologic treatments for rheumatologic disease (Abbott, Wyeth, Schering-Plough, Bristol-Myers Squibb, Roche, and UCB-Nordic), DANBIO is approved by the Danish National Board of Health as a national quality registry, Dr. Hetland and her associates wrote (Arthritis Rheum. 2010;62:22-32).

This study is believed to be the first direct comparison between adalimumab, etanercept, and infliximab and the ability of the three agents to elicit treatment goals including remission, they noted.

All patients included in the study had RA and had been treated with one or more conventional disease-modifying antirheumatic drugs (DMARDs), but those treatments had failed, and one of the three biologic agents was initiated. Concomitant methotrexate or other DMARD and prednisolone were administered based on the decision of the treating rheumatologist.

The initial study population comprised 2,326 patients, of whom 449 withdrew prior to the first 6 months of the study. Of those 449, 52% withdrew because of lack of efficacy and 38% from adverse events.

Among the 1,877 patients who had not withdrawn, an ACR 70 (American College of Rheumatology 70) response was achieved after 6 months in 19% of them (Arthritis Rheum. 1995;38:727-35), a good response by the EULAR (European League Against Rheumatism) criteria in 41% of them (Arthritis Rheum. 1996;39:34-40), remission by DAS28 (Disease Activity Score in 28 joints) in 25% of them, and CDAI (Clinical Disease Activity Index) remission in 13%.

Older age, low functional status as reflected in a high score on the Health Assessment Questionnaire, and concomitant prednisolone treatment were negative predictors of an ACR 70 response, whereas concomitant methotrexate, male sex, number of previous DMARD treatments, and disease duration were not predictors.

The patterns were similar for all outcome measures at 6 and 12 months, according to Dr. Hetland and her associates.

Overall, the crude treatment response rates after 6 and 12 months were highest for adalimumab (544 patients), intermediate for etanercept (425), and poorest for infliximab (908).

After correction for withdrawals from the study, ACR 70 was achieved at 6 months by 19% of those receiving adalimumab, by 17% of those using etanercept, and by 11% of those on infliximab. A good EULAR response was reported at 6 months in 41%, 34%, and 27%, respectively.

Similarly, DAS28 remission at 6 months occurred in 26% with adalimumab, 21% with etanercept, and 17% with infliximab; CDAI remission occurred in 15%, 10%, and 8%, respectively.

Combination therapy with methotrexate and prednisolone was used more often by those taking infliximab than by those using the other two TNF-alpha inhibitors.

After adjustment for that, as well as previous DMARD use, sex, age, disease duration, seropositivity, and baseline functional status, the odds ratios for achieving an ACR 70 response after 6 months of treatment were 2.05 for adalimumab and 1.78 for etanercept, compared with infliximab.

Adalimumab and etanercept were not significantly different, the investigators reported.

The odds ratios for adalimumab vs. infliximab were statistically significant for all outcome measures, ranging from 1.78 to 2.76. For etanercept vs. infliximab, odds ratios ranged from 1.16 to 1.99, which were statistically significant for ACR 70 and EULAR response measures, but not for the two remission outcomes.

Adalimumab produced a significantly higher EULAR good response (OR, 1.49) and CDAI remission (OR, 1.58) than did etanercept.

Drug adherence was highest for etanercept and lowest for infliximab. At 48 months, unadjusted adherence rates were 52% for adalimumab, 56% for etanercept, and 41% for infliximab, Dr. Hetland and her associates said.

Disclosures: This study was supported by unrestricted grants to DANBIO from its participating companies, which had no role in the study design, nor the collection, analysis, or interpretation of the data or the decision to submit the manuscript for publication.

Dr. Hetland's work on this study was supported by a grant from the Danish Rheumatism Association and a private foundation.

She has received consulting fees, speaking fees, and/or research grants of less than $10,000 each from all of the companies (except Bristol-Myers Squibb) that were involved in DANBIO, and grants of more than $10,000 each from all the participating companies on behalf of DANBIO.

Several of the 14 other coauthors have similar disclosures.

Major Finding: Mothers with rheumatoid arthritis were 1.47 times more likely than unaffected mothers to have a low-birth-weight baby, and 1.20 times more likely to have a baby deemed small for gestational age.

Data Source: From two large databases, researchers selected a sample of women who gave birth (1,912 with RA and 9560 controls).

Disclosures: The researchers made no disclosures.

Pregnant women with rheumatoid arthritis face an increased risk of adverse obstetric outcomes, and they deserve heightened prenatal attention, according to a recent report in the February issue of the Annals of Rheumatic Diseases.

Specifically, mothers with rheumatoid arthritis (RA) were 1.47 times more likely than unaffected mothers to have a low-birth-weight baby and 1.20 times more likely to have a baby deemed small for gestational age.

Women with RA also had a higher risk for developing preeclampsia (adjusted odds ratio, 2.22) or having to undergo a cesarian section (adjusted OR, 1.19), according to investigators from Taipei (Taiwan) Medical University (Ann. Rheum. Dis. 2010 Feb. [doi:10.1136/ard.2008.105262]).

“Our findings suggest a need for more intensive prenatal care among pregnant women with RA. In addition, early intervention should be considered to counter potential adverse obstetric outcomes for pregnant women with RA,” according to Herng Ching Lin, Ph.D., and associates, all of whom are with the university's school of health care administration.

Investigators used two databases in their analysis. The first was the Taiwan National Health Insurance Research Dataset (NHIRD), which included inpatient and ambulatory care claims from 1996 to 2003, and the second was the 2001-2003 National Birth Certificate Registry (NBCR), which is maintained by the government of Taiwan.

From the nearly 500,000 women who had live singleton births in Taiwan between 2001 and 2003, the investigators identified 1,912 mothers with RA (ICD-9-CM, code 714.0) and compared their pregnancy outcomes with those of 9,560 controls who were matched to the cases by age, parity, and year of delivery. The diagnosis of RA in the cases was usually made by a rheumatologist and based on clinical symptoms, radiographic changes, and the presence of rheumatoid factor.

Women with chronic diseases such as hypertension or diabetes that could increase the risk of adverse pregnancy outcomes were excluded.

The two groups of women did not differ significantly in their sociodemographic variables such as marital status, level of education, and household income.

The women with RA were no more likely than their unaffected peers to have preterm births. For women with RA, the mean gestational age was 38.4 weeks (range, 27-43); the mean gestational ages for mothers with and without RA were 38.3 weeks (range, 27-43) and 38.5 weeks (range, 29-41), respectively.

According to the authors, one strength of the study was its homogenous population: More than 98% of Taiwan's residents are of Chinese Han ethnicity.

Although this may have minimized the possibility that race affected the results, it may have also limited whether the results can be generalized to other ethnic groups.

Another strength is its large sample size.

One important limitation of the study was that the NHIRD did not include complete information about RA medications that were taken during pregnancy, a potentially important confounding factor.

A second limitation was that study participants were not differentiated according to RA severity.

Major Finding: Mothers with rheumatoid arthritis were 1.47 times more likely than unaffected mothers to have a low-birth-weight baby, and 1.20 times more likely to have a baby deemed small for gestational age.

Data Source: From two large databases, researchers selected a sample of women who gave birth (1,912 with RA and 9560 controls).

Disclosures: The researchers made no disclosures.

Pregnant women with rheumatoid arthritis face an increased risk of adverse obstetric outcomes, and they deserve heightened prenatal attention, according to a recent report in the February issue of the Annals of Rheumatic Diseases.

Specifically, mothers with rheumatoid arthritis (RA) were 1.47 times more likely than unaffected mothers to have a low-birth-weight baby and 1.20 times more likely to have a baby deemed small for gestational age.

Women with RA also had a higher risk for developing preeclampsia (adjusted odds ratio, 2.22) or having to undergo a cesarian section (adjusted OR, 1.19), according to investigators from Taipei (Taiwan) Medical University (Ann. Rheum. Dis. 2010 Feb. [doi:10.1136/ard.2008.105262]).

“Our findings suggest a need for more intensive prenatal care among pregnant women with RA. In addition, early intervention should be considered to counter potential adverse obstetric outcomes for pregnant women with RA,” according to Herng Ching Lin, Ph.D., and associates, all of whom are with the university's school of health care administration.

Investigators used two databases in their analysis. The first was the Taiwan National Health Insurance Research Dataset (NHIRD), which included inpatient and ambulatory care claims from 1996 to 2003, and the second was the 2001-2003 National Birth Certificate Registry (NBCR), which is maintained by the government of Taiwan.

From the nearly 500,000 women who had live singleton births in Taiwan between 2001 and 2003, the investigators identified 1,912 mothers with RA (ICD-9-CM, code 714.0) and compared their pregnancy outcomes with those of 9,560 controls who were matched to the cases by age, parity, and year of delivery. The diagnosis of RA in the cases was usually made by a rheumatologist and based on clinical symptoms, radiographic changes, and the presence of rheumatoid factor.

Women with chronic diseases such as hypertension or diabetes that could increase the risk of adverse pregnancy outcomes were excluded.

The two groups of women did not differ significantly in their sociodemographic variables such as marital status, level of education, and household income.

The women with RA were no more likely than their unaffected peers to have preterm births. For women with RA, the mean gestational age was 38.4 weeks (range, 27-43); the mean gestational ages for mothers with and without RA were 38.3 weeks (range, 27-43) and 38.5 weeks (range, 29-41), respectively.

According to the authors, one strength of the study was its homogenous population: More than 98% of Taiwan's residents are of Chinese Han ethnicity.

Although this may have minimized the possibility that race affected the results, it may have also limited whether the results can be generalized to other ethnic groups.

Another strength is its large sample size.

One important limitation of the study was that the NHIRD did not include complete information about RA medications that were taken during pregnancy, a potentially important confounding factor.

A second limitation was that study participants were not differentiated according to RA severity.

Major Finding: Mothers with rheumatoid arthritis were 1.47 times more likely than unaffected mothers to have a low-birth-weight baby, and 1.20 times more likely to have a baby deemed small for gestational age.

Data Source: From two large databases, researchers selected a sample of women who gave birth (1,912 with RA and 9560 controls).

Disclosures: The researchers made no disclosures.

Pregnant women with rheumatoid arthritis face an increased risk of adverse obstetric outcomes, and they deserve heightened prenatal attention, according to a recent report in the February issue of the Annals of Rheumatic Diseases.

Specifically, mothers with rheumatoid arthritis (RA) were 1.47 times more likely than unaffected mothers to have a low-birth-weight baby and 1.20 times more likely to have a baby deemed small for gestational age.

Women with RA also had a higher risk for developing preeclampsia (adjusted odds ratio, 2.22) or having to undergo a cesarian section (adjusted OR, 1.19), according to investigators from Taipei (Taiwan) Medical University (Ann. Rheum. Dis. 2010 Feb. [doi:10.1136/ard.2008.105262]).

“Our findings suggest a need for more intensive prenatal care among pregnant women with RA. In addition, early intervention should be considered to counter potential adverse obstetric outcomes for pregnant women with RA,” according to Herng Ching Lin, Ph.D., and associates, all of whom are with the university's school of health care administration.

Investigators used two databases in their analysis. The first was the Taiwan National Health Insurance Research Dataset (NHIRD), which included inpatient and ambulatory care claims from 1996 to 2003, and the second was the 2001-2003 National Birth Certificate Registry (NBCR), which is maintained by the government of Taiwan.

From the nearly 500,000 women who had live singleton births in Taiwan between 2001 and 2003, the investigators identified 1,912 mothers with RA (ICD-9-CM, code 714.0) and compared their pregnancy outcomes with those of 9,560 controls who were matched to the cases by age, parity, and year of delivery. The diagnosis of RA in the cases was usually made by a rheumatologist and based on clinical symptoms, radiographic changes, and the presence of rheumatoid factor.

Women with chronic diseases such as hypertension or diabetes that could increase the risk of adverse pregnancy outcomes were excluded.

The two groups of women did not differ significantly in their sociodemographic variables such as marital status, level of education, and household income.

The women with RA were no more likely than their unaffected peers to have preterm births. For women with RA, the mean gestational age was 38.4 weeks (range, 27-43); the mean gestational ages for mothers with and without RA were 38.3 weeks (range, 27-43) and 38.5 weeks (range, 29-41), respectively.

According to the authors, one strength of the study was its homogenous population: More than 98% of Taiwan's residents are of Chinese Han ethnicity.

Although this may have minimized the possibility that race affected the results, it may have also limited whether the results can be generalized to other ethnic groups.

Another strength is its large sample size.

One important limitation of the study was that the NHIRD did not include complete information about RA medications that were taken during pregnancy, a potentially important confounding factor.

A second limitation was that study participants were not differentiated according to RA severity.

Comorbidities, rather than the effects of inflammatory joint disease, may be why some patients with rheumatoid arthritis remain functionally disabled despite effective treatment for their arthritis.

This study included 380 RA patients from an outpatient clinic with a wide range of disease activity, disease duration, and comorbid conditions, according to Dr. Helga Radner and her associates from the Medical University of Vienna.

The study was based on serial measurements taken from more than 1,600 patient visits between June 2007 and July 2008. Physical disability was measured using the HAQ (Health Assessment Questionnaire) disability index. The Charlson Comorbidity Index (CCI), adjusted for age, was used to assess comorbidity burden, with differing weights given to comorbid conditions such as myocardial infarction (weight = 1), diabetes mellitus with complications (weight = 2), or AIDS (weight = 6).

Analysis of variance indicated a consistent increase in physical disability with increasing comorbidity burden (P less than .01), even after adjustment for disease activity, sex, or disease duration (Ann. Rheum. Dis. 2010 [doi:10.1136/ard.2009. 118430]).

The influential effect of comorbidities on functional disability in patients with RA was seen across all levels of RA disease activity, as measured by the CDAI (Clinical Disease Activity Index). For RA patients with low or moderate/high disease severity, having one or more comorbidities added to the levels of functional disability, “reflecting the well-known contribution of [RA] disease activity to impairment of physical function,” Dr. Radner and her associates said. However, even patients who were thought to be in remission for RA showed significant increases in functional disability when comorbidities were present (P less than .01).

“Based on our analyses, the average HAQ in a group of patients with several comorbid conditions would be somewhere around 0.6, even if the best possible treatment was used. This floor effect of functional improvement is an important aspect when evidence of therapeutic efficacy needs to be provided, such as for reimbursement of interventions,” the authors wrote.

Disclosures: Dr. Radner and her associates report having no conflicts of interest.

Comorbidities, rather than the effects of inflammatory joint disease, may be why some patients with rheumatoid arthritis remain functionally disabled despite effective treatment for their arthritis.

This study included 380 RA patients from an outpatient clinic with a wide range of disease activity, disease duration, and comorbid conditions, according to Dr. Helga Radner and her associates from the Medical University of Vienna.

The study was based on serial measurements taken from more than 1,600 patient visits between June 2007 and July 2008. Physical disability was measured using the HAQ (Health Assessment Questionnaire) disability index. The Charlson Comorbidity Index (CCI), adjusted for age, was used to assess comorbidity burden, with differing weights given to comorbid conditions such as myocardial infarction (weight = 1), diabetes mellitus with complications (weight = 2), or AIDS (weight = 6).

Analysis of variance indicated a consistent increase in physical disability with increasing comorbidity burden (P less than .01), even after adjustment for disease activity, sex, or disease duration (Ann. Rheum. Dis. 2010 [doi:10.1136/ard.2009. 118430]).

The influential effect of comorbidities on functional disability in patients with RA was seen across all levels of RA disease activity, as measured by the CDAI (Clinical Disease Activity Index). For RA patients with low or moderate/high disease severity, having one or more comorbidities added to the levels of functional disability, “reflecting the well-known contribution of [RA] disease activity to impairment of physical function,” Dr. Radner and her associates said. However, even patients who were thought to be in remission for RA showed significant increases in functional disability when comorbidities were present (P less than .01).

“Based on our analyses, the average HAQ in a group of patients with several comorbid conditions would be somewhere around 0.6, even if the best possible treatment was used. This floor effect of functional improvement is an important aspect when evidence of therapeutic efficacy needs to be provided, such as for reimbursement of interventions,” the authors wrote.

Disclosures: Dr. Radner and her associates report having no conflicts of interest.

Comorbidities, rather than the effects of inflammatory joint disease, may be why some patients with rheumatoid arthritis remain functionally disabled despite effective treatment for their arthritis.

This study included 380 RA patients from an outpatient clinic with a wide range of disease activity, disease duration, and comorbid conditions, according to Dr. Helga Radner and her associates from the Medical University of Vienna.

The study was based on serial measurements taken from more than 1,600 patient visits between June 2007 and July 2008. Physical disability was measured using the HAQ (Health Assessment Questionnaire) disability index. The Charlson Comorbidity Index (CCI), adjusted for age, was used to assess comorbidity burden, with differing weights given to comorbid conditions such as myocardial infarction (weight = 1), diabetes mellitus with complications (weight = 2), or AIDS (weight = 6).

Analysis of variance indicated a consistent increase in physical disability with increasing comorbidity burden (P less than .01), even after adjustment for disease activity, sex, or disease duration (Ann. Rheum. Dis. 2010 [doi:10.1136/ard.2009. 118430]).

The influential effect of comorbidities on functional disability in patients with RA was seen across all levels of RA disease activity, as measured by the CDAI (Clinical Disease Activity Index). For RA patients with low or moderate/high disease severity, having one or more comorbidities added to the levels of functional disability, “reflecting the well-known contribution of [RA] disease activity to impairment of physical function,” Dr. Radner and her associates said. However, even patients who were thought to be in remission for RA showed significant increases in functional disability when comorbidities were present (P less than .01).

“Based on our analyses, the average HAQ in a group of patients with several comorbid conditions would be somewhere around 0.6, even if the best possible treatment was used. This floor effect of functional improvement is an important aspect when evidence of therapeutic efficacy needs to be provided, such as for reimbursement of interventions,” the authors wrote.

Disclosures: Dr. Radner and her associates report having no conflicts of interest.

Major Finding: The study confirmed that the incidence of RA increases during the first 2 years post partum.

Data Source: NOR-DMARD Registry and the Medical Birth Registry of Norway.

Disclosures: Research was supported by the liaison committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. The NOR-DMARD registry is supported by all makers of biologic drugs for RA in Europe.

By linking two Norwegian national data registries, investigators confirmed previous findings that the incidence of rheumatoid arthritis is increased in women in the 2 years following delivery, compared with the subsequent 2 years post partum. The results also showed an elevated incidence of other chronic arthritides in the first 2 postpartum years, according to a report by Dr. Marianne Wallenius from the department of rheumatology of St. Olav's Hospital in Trondheim, Norway.

These studies may contribute to a better understanding of the fundamental question of why one person gets RA and another does not,” noted Dr. Radboud J.E.M. Dolhain of Erasmus University Medical Centre, Rotterdam, the Netherlands, in an accompanying editorial (Ann. Rheum. Dis. 2010;69:317-8).

One hypothesis is that pregnancy exerts a protective effect on RA and other arthritides, which then disappears after delivery, allowing disease to flare. However, this study did not look at incidence during pregnancy. More epidemiologic data are needed “to determine whether this is a true increased incidence or whether rather the incidence of RA and other forms of arthritis is postponed to after delivery,” according to Dr. Dolhain.

The investigators took a unique approach to studying the incidence of RA and other chronic arthritides following pregnancy. They linked data from a registry of people with inflammatory arthropathies who were taking disease-modifying antirheumatic drugs (the NOR-DMARD Registry) with the Medical Birth Registry of Norway that has recorded all births in Norway since 1967. The investigators were able to locate 293 women with arthritis whose disease was first diagnosed after delivery. Of these, 183 were diagnosed with RA and 110 with other chronic arthritides (OCA), including 51 with psoriatic arthritis, 14 with ankylosing spondylitides, and 45 with unspecified arthritis.

Of those with RA, 38% (69 women) were diagnosed in the first 2 years post partum, compared with 28% (31 women) who were diagnosed with OCA. The results were not significantly different (P = .09).

RA incidence peaked in the first 2 years after pregnancy, compared with the subsequent 2 years for those who were diagnosed solely with RA (incident rate ratio, 1.73; P = .01) or for the entire RA-plus-OCA group (IRR, 1.44; P = .04) after all pregnancies were considered, but not for those who were diagnosed only with OCA (IRR, 1.05; P = .86). Investigators made similar findings when they limited the group to those who were diagnosed only after the first pregnancy (Ann. Rheum. Dis. 2010;69:332-6).

The investigators suggested that the lack of statistical significance for the OCA group may be attributed to the group's being too small, with rather wide confidence intervals around the IRR estimate. One reason the OCA group may have been small was that the NOR-DMARD Registry included patients who had developed a level of disease that required treatment with DMARDs and/or biologic agents, thereby excluding patients with milder disease who did not require such medication.

Major Finding: The study confirmed that the incidence of RA increases during the first 2 years post partum.

Data Source: NOR-DMARD Registry and the Medical Birth Registry of Norway.

Disclosures: Research was supported by the liaison committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. The NOR-DMARD registry is supported by all makers of biologic drugs for RA in Europe.

By linking two Norwegian national data registries, investigators confirmed previous findings that the incidence of rheumatoid arthritis is increased in women in the 2 years following delivery, compared with the subsequent 2 years post partum. The results also showed an elevated incidence of other chronic arthritides in the first 2 postpartum years, according to a report by Dr. Marianne Wallenius from the department of rheumatology of St. Olav's Hospital in Trondheim, Norway.

These studies may contribute to a better understanding of the fundamental question of why one person gets RA and another does not,” noted Dr. Radboud J.E.M. Dolhain of Erasmus University Medical Centre, Rotterdam, the Netherlands, in an accompanying editorial (Ann. Rheum. Dis. 2010;69:317-8).

One hypothesis is that pregnancy exerts a protective effect on RA and other arthritides, which then disappears after delivery, allowing disease to flare. However, this study did not look at incidence during pregnancy. More epidemiologic data are needed “to determine whether this is a true increased incidence or whether rather the incidence of RA and other forms of arthritis is postponed to after delivery,” according to Dr. Dolhain.

The investigators took a unique approach to studying the incidence of RA and other chronic arthritides following pregnancy. They linked data from a registry of people with inflammatory arthropathies who were taking disease-modifying antirheumatic drugs (the NOR-DMARD Registry) with the Medical Birth Registry of Norway that has recorded all births in Norway since 1967. The investigators were able to locate 293 women with arthritis whose disease was first diagnosed after delivery. Of these, 183 were diagnosed with RA and 110 with other chronic arthritides (OCA), including 51 with psoriatic arthritis, 14 with ankylosing spondylitides, and 45 with unspecified arthritis.

Of those with RA, 38% (69 women) were diagnosed in the first 2 years post partum, compared with 28% (31 women) who were diagnosed with OCA. The results were not significantly different (P = .09).

RA incidence peaked in the first 2 years after pregnancy, compared with the subsequent 2 years for those who were diagnosed solely with RA (incident rate ratio, 1.73; P = .01) or for the entire RA-plus-OCA group (IRR, 1.44; P = .04) after all pregnancies were considered, but not for those who were diagnosed only with OCA (IRR, 1.05; P = .86). Investigators made similar findings when they limited the group to those who were diagnosed only after the first pregnancy (Ann. Rheum. Dis. 2010;69:332-6).

The investigators suggested that the lack of statistical significance for the OCA group may be attributed to the group's being too small, with rather wide confidence intervals around the IRR estimate. One reason the OCA group may have been small was that the NOR-DMARD Registry included patients who had developed a level of disease that required treatment with DMARDs and/or biologic agents, thereby excluding patients with milder disease who did not require such medication.

Major Finding: The study confirmed that the incidence of RA increases during the first 2 years post partum.

Data Source: NOR-DMARD Registry and the Medical Birth Registry of Norway.

Disclosures: Research was supported by the liaison committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. The NOR-DMARD registry is supported by all makers of biologic drugs for RA in Europe.

By linking two Norwegian national data registries, investigators confirmed previous findings that the incidence of rheumatoid arthritis is increased in women in the 2 years following delivery, compared with the subsequent 2 years post partum. The results also showed an elevated incidence of other chronic arthritides in the first 2 postpartum years, according to a report by Dr. Marianne Wallenius from the department of rheumatology of St. Olav's Hospital in Trondheim, Norway.

These studies may contribute to a better understanding of the fundamental question of why one person gets RA and another does not,” noted Dr. Radboud J.E.M. Dolhain of Erasmus University Medical Centre, Rotterdam, the Netherlands, in an accompanying editorial (Ann. Rheum. Dis. 2010;69:317-8).

One hypothesis is that pregnancy exerts a protective effect on RA and other arthritides, which then disappears after delivery, allowing disease to flare. However, this study did not look at incidence during pregnancy. More epidemiologic data are needed “to determine whether this is a true increased incidence or whether rather the incidence of RA and other forms of arthritis is postponed to after delivery,” according to Dr. Dolhain.

The investigators took a unique approach to studying the incidence of RA and other chronic arthritides following pregnancy. They linked data from a registry of people with inflammatory arthropathies who were taking disease-modifying antirheumatic drugs (the NOR-DMARD Registry) with the Medical Birth Registry of Norway that has recorded all births in Norway since 1967. The investigators were able to locate 293 women with arthritis whose disease was first diagnosed after delivery. Of these, 183 were diagnosed with RA and 110 with other chronic arthritides (OCA), including 51 with psoriatic arthritis, 14 with ankylosing spondylitides, and 45 with unspecified arthritis.

Of those with RA, 38% (69 women) were diagnosed in the first 2 years post partum, compared with 28% (31 women) who were diagnosed with OCA. The results were not significantly different (P = .09).

RA incidence peaked in the first 2 years after pregnancy, compared with the subsequent 2 years for those who were diagnosed solely with RA (incident rate ratio, 1.73; P = .01) or for the entire RA-plus-OCA group (IRR, 1.44; P = .04) after all pregnancies were considered, but not for those who were diagnosed only with OCA (IRR, 1.05; P = .86). Investigators made similar findings when they limited the group to those who were diagnosed only after the first pregnancy (Ann. Rheum. Dis. 2010;69:332-6).

The investigators suggested that the lack of statistical significance for the OCA group may be attributed to the group's being too small, with rather wide confidence intervals around the IRR estimate. One reason the OCA group may have been small was that the NOR-DMARD Registry included patients who had developed a level of disease that required treatment with DMARDs and/or biologic agents, thereby excluding patients with milder disease who did not require such medication.

Elevated concentrations of proinflammatory cytokines, cytokine-related factors, and chemokines, indicating activation of the immune system, have been found in the blood of people years before they developed symptoms of rheumatoid arthritis that involved the joints, according to a report by Heidi Kokkonen and coinvestigators at Umeå (Sweden) University. The study was published in the February 2010 issue of Arthritis and Rheumatism.

By comparing blood samples of people diagnosed with RA to normal controls and “prepatients” (those who go on to develop RA), investigators said that they hope the results will help predict an individual's risk of developing RA.

The investigators analyzed samples from the Medical Biobank of Northern Sweden, which invites all adult individuals from the county of Västerbotten to contribute blood samples. Within this population-based cohort, there were 86 individuals who went on develop inflammatory joint disease that fulfilled American College of Rheumatology classification criteria for RA after their donation of blood. For these prepatients, the median time predating the onset of symptoms was 3.3 years (range, 1.1-5 years). Of the 86 prepatients, 69 also provided blood samples at the time of RA diagnosis. For every prepatient, three control subjects were randomly selected from the Biobank register and matched for sex, age, and area of residence.

Several cytokines, cytokine-related factors, and chemokines were upregulated in prepatients, compared with controls. The greatest increases were noted for the Th2-related cytokines, eotaxin, and interleukin-4, with elevated levels also observed for Th1 cytokines, IL-12, interferon-gamma, and IL-10.

A multivariate classification algorithm known as the random forest method, similar to decision trees, was used to estimate which groups of cytokines, cytokine-related factors, or chemokines could best distinguish a particular group of patients. For prepatients, characteristic changes were related to both the Th1 and Th2 lineage, and to Treg cells, representing the adaptive immune system, the authors wrote. Elevation of IL-17 levels did not reach statistical significance.

Levels of at least two-thirds of the cytokines or cytokine-related factors were above the median values for control subjects in 50 of 85 prepatients.

Of the chemokines, MCP-1 and MIP-1 alpha levels were significantly increased in prepatients, compared with controls, as were the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte–colony stimulating factor (G-CSF).

When the authors calculated the sensitivity and specificity of different factors for the development of RA in prepatients, they found that after anti-CCP antibodies and IgM rheumatoid factor (IgM-RF), eotaxin had the highest sensitivity (22.4%) and specificity (95.3%), with an odds ratio of 5.8. About one-half of the cytokines and cytokine-related factors that had significant predicative value for the development of RA in prepatients were related to Th1, Th2, and Treg cells. When all analyzed factors and anti-CCP antibodies were included, the sensitivity level rose to 51.2%, with a specificity of 91.9% for predicting the development of RA among prepatients and control subjects.

The factors distinguishing individuals before and after the onset of RA represented a more general immunologic response, as well as stromal cells and angiogenic factors. After RA diagnosis, significant increases were seen for most of the factors that were measured. IL-17 concentrations actually decreased after RA diagnosis. “This observation endorses the role of IL-17 in the initiating phase [of RA], and, as the pathogenesis progresses, other factors are subsequently brought into action,” wrote the authors (Arthritis Rheum. 2010;62:383-91).

Although the authors were unable to conclude which agent initiates RA pathogenesis, they suggested that their findings present an opportunity for better predicting the risk of developing RA and intervening at an early stage to possibly prevent disease progression.

Elevated concentrations of proinflammatory cytokines, cytokine-related factors, and chemokines, indicating activation of the immune system, have been found in the blood of people years before they developed symptoms of rheumatoid arthritis that involved the joints, according to a report by Heidi Kokkonen and coinvestigators at Umeå (Sweden) University. The study was published in the February 2010 issue of Arthritis and Rheumatism.

By comparing blood samples of people diagnosed with RA to normal controls and “prepatients” (those who go on to develop RA), investigators said that they hope the results will help predict an individual's risk of developing RA.

The investigators analyzed samples from the Medical Biobank of Northern Sweden, which invites all adult individuals from the county of Västerbotten to contribute blood samples. Within this population-based cohort, there were 86 individuals who went on develop inflammatory joint disease that fulfilled American College of Rheumatology classification criteria for RA after their donation of blood. For these prepatients, the median time predating the onset of symptoms was 3.3 years (range, 1.1-5 years). Of the 86 prepatients, 69 also provided blood samples at the time of RA diagnosis. For every prepatient, three control subjects were randomly selected from the Biobank register and matched for sex, age, and area of residence.

Several cytokines, cytokine-related factors, and chemokines were upregulated in prepatients, compared with controls. The greatest increases were noted for the Th2-related cytokines, eotaxin, and interleukin-4, with elevated levels also observed for Th1 cytokines, IL-12, interferon-gamma, and IL-10.

A multivariate classification algorithm known as the random forest method, similar to decision trees, was used to estimate which groups of cytokines, cytokine-related factors, or chemokines could best distinguish a particular group of patients. For prepatients, characteristic changes were related to both the Th1 and Th2 lineage, and to Treg cells, representing the adaptive immune system, the authors wrote. Elevation of IL-17 levels did not reach statistical significance.

Levels of at least two-thirds of the cytokines or cytokine-related factors were above the median values for control subjects in 50 of 85 prepatients.

Of the chemokines, MCP-1 and MIP-1 alpha levels were significantly increased in prepatients, compared with controls, as were the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte–colony stimulating factor (G-CSF).

When the authors calculated the sensitivity and specificity of different factors for the development of RA in prepatients, they found that after anti-CCP antibodies and IgM rheumatoid factor (IgM-RF), eotaxin had the highest sensitivity (22.4%) and specificity (95.3%), with an odds ratio of 5.8. About one-half of the cytokines and cytokine-related factors that had significant predicative value for the development of RA in prepatients were related to Th1, Th2, and Treg cells. When all analyzed factors and anti-CCP antibodies were included, the sensitivity level rose to 51.2%, with a specificity of 91.9% for predicting the development of RA among prepatients and control subjects.

The factors distinguishing individuals before and after the onset of RA represented a more general immunologic response, as well as stromal cells and angiogenic factors. After RA diagnosis, significant increases were seen for most of the factors that were measured. IL-17 concentrations actually decreased after RA diagnosis. “This observation endorses the role of IL-17 in the initiating phase [of RA], and, as the pathogenesis progresses, other factors are subsequently brought into action,” wrote the authors (Arthritis Rheum. 2010;62:383-91).

Although the authors were unable to conclude which agent initiates RA pathogenesis, they suggested that their findings present an opportunity for better predicting the risk of developing RA and intervening at an early stage to possibly prevent disease progression.

Elevated concentrations of proinflammatory cytokines, cytokine-related factors, and chemokines, indicating activation of the immune system, have been found in the blood of people years before they developed symptoms of rheumatoid arthritis that involved the joints, according to a report by Heidi Kokkonen and coinvestigators at Umeå (Sweden) University. The study was published in the February 2010 issue of Arthritis and Rheumatism.

By comparing blood samples of people diagnosed with RA to normal controls and “prepatients” (those who go on to develop RA), investigators said that they hope the results will help predict an individual's risk of developing RA.

The investigators analyzed samples from the Medical Biobank of Northern Sweden, which invites all adult individuals from the county of Västerbotten to contribute blood samples. Within this population-based cohort, there were 86 individuals who went on develop inflammatory joint disease that fulfilled American College of Rheumatology classification criteria for RA after their donation of blood. For these prepatients, the median time predating the onset of symptoms was 3.3 years (range, 1.1-5 years). Of the 86 prepatients, 69 also provided blood samples at the time of RA diagnosis. For every prepatient, three control subjects were randomly selected from the Biobank register and matched for sex, age, and area of residence.

Several cytokines, cytokine-related factors, and chemokines were upregulated in prepatients, compared with controls. The greatest increases were noted for the Th2-related cytokines, eotaxin, and interleukin-4, with elevated levels also observed for Th1 cytokines, IL-12, interferon-gamma, and IL-10.

A multivariate classification algorithm known as the random forest method, similar to decision trees, was used to estimate which groups of cytokines, cytokine-related factors, or chemokines could best distinguish a particular group of patients. For prepatients, characteristic changes were related to both the Th1 and Th2 lineage, and to Treg cells, representing the adaptive immune system, the authors wrote. Elevation of IL-17 levels did not reach statistical significance.

Levels of at least two-thirds of the cytokines or cytokine-related factors were above the median values for control subjects in 50 of 85 prepatients.

Of the chemokines, MCP-1 and MIP-1 alpha levels were significantly increased in prepatients, compared with controls, as were the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte–colony stimulating factor (G-CSF).

When the authors calculated the sensitivity and specificity of different factors for the development of RA in prepatients, they found that after anti-CCP antibodies and IgM rheumatoid factor (IgM-RF), eotaxin had the highest sensitivity (22.4%) and specificity (95.3%), with an odds ratio of 5.8. About one-half of the cytokines and cytokine-related factors that had significant predicative value for the development of RA in prepatients were related to Th1, Th2, and Treg cells. When all analyzed factors and anti-CCP antibodies were included, the sensitivity level rose to 51.2%, with a specificity of 91.9% for predicting the development of RA among prepatients and control subjects.

The factors distinguishing individuals before and after the onset of RA represented a more general immunologic response, as well as stromal cells and angiogenic factors. After RA diagnosis, significant increases were seen for most of the factors that were measured. IL-17 concentrations actually decreased after RA diagnosis. “This observation endorses the role of IL-17 in the initiating phase [of RA], and, as the pathogenesis progresses, other factors are subsequently brought into action,” wrote the authors (Arthritis Rheum. 2010;62:383-91).

Although the authors were unable to conclude which agent initiates RA pathogenesis, they suggested that their findings present an opportunity for better predicting the risk of developing RA and intervening at an early stage to possibly prevent disease progression.