Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

ABSTRACTS in PERSPECTIVE based on presentations from the 72nd Annual Meeting of the American College of Rheumatology

San Francisco, California / October 24-29, 2008

EDITORIAL REVIEW:

Michael R. Starr, MD, FRCPC

Division of Rheumatology, Montreal General Hospital, Assistant Professor of Medicine, McGill University, Montreal, Quebec

Rheumatoid arthritis (RA) affects more than 2 million adults in the US, leading to high rates of morbidity and disability despite recent advances in diagnosis and treatment. About 40% of employed patients with RA stop working within five years of diagnosis.

Although RA has no cure, early diagnosis and aggressive treatment can improve the outlook for many patients. Dr. Vappu Rantalaiho, Tampere University Hospital, Finland reported updated results from the FIN-RACo (Finnish Rheumatoid Arthritis Combination Therapy) initial treatment strategy, consisting of three disease-modifying antirehumatic drugs (DMARDs) plus prednisolone. After 11 years of followup, initial aggressive therapy resulted in significantly less radiographic progression (P=0.039) compared to initial treatment with a single DMARD. Additionally, three times as many patients in the FIN-RACo group had no erosions at 11 years compared to the patients treated with a single DMARD.

Within the past decade, laboratory and clinical studies have implicated tumour necrosis factor (TNF) as a major contributor to the pathogenesis of RA. The research formed the basis for development of biologic agents that target TNF, the first of which being infliximab. Extensive clinical evaluation has found TNF inhibitors effective in controlling pain, arresting the disease process and improving the quality of life of patients affected by RA. Though not devoid of adverse events, the anti-TNF agents generally have proved to be safe and well tolerated.

TNF Inhibition in Early Disease

Conventional approaches of early RA treatment have usually relied on monotherapy and step-up regimens. An accumulation of data has shown that beginning treatment with the combination of methotrexate and a TNF-a inhibitor offers advantages over strategies based on monotherapy and step-up care. The French GUEPARD trial provided a demonstration of the advantages of combination therapy with a TNF-a inhibitor. Investigators randomized patients with early RA to initial treatment with methotrexate alone or in combination with adalimumab. Treatment was targeted to a low disease activity state (LDAS), defined as a DAS28- ESR (erythrocyte sedimentation rate) <3.2. The TNF-a inhibitor was withdrawn if LDAS was maintained for three months. The combination therapy had a more rapid onset of activity, reflected in a significant difference in LDAS at 12 weeks (P=0.001) and 12-week AUC (P<0.0001). The two strategies had similar rates of LDAS at 52 weeks.

Dr. Désirée van der Heijde, Leiden University Medical Center, The Netherlands, reported five-year results from another study of patients with early RA initially treated with a methotrexate/TNF inhibitor combination therapy. During the two-year randomized phase of the study, patients received methotrexate or adalimumab, alone or in combination, followed by open-label adalimumab for an additional three years. Half of patients started on combination therapy had no radiographic progression at five years, compared with a third of patients treated with a single agent during the first two years. Moreover, 35% of the combination group had no radiographic progression, clinical remission, and normal function, compared with 13 to 14% of the monotherapy groups.

Observed differences in clinician and patient assessments of RA status have led to some debate about the need for more emphasis on patient-reported outcomes. The patient viewpoint was the focus of a report from a randomized comparison of methotrexate with or without etanercept as initial therapy for early, active RA. After 52 weeks of followup, patients randomized to initial combination therapy had significantly better results on a measure of health state (P<0.05 to P<0.001), self-assessed health status (P<0.01 to P<0.001), and patient-rated fatigue (P<0.05 to P<0.001). Additionally, all eight domains of the Short-form (SF)-36 medical outcomes form favoured combination therapy, including significant differences in physical functioning (P<0.001), vitality (P=0.02), bodily pain (P<0.001), and role emotional (P=0.02). Presented by Dr. Patrick Durez, Catholic University of Louvain, Belgium, the data also showed that even in the earliest stages, RA causes substantial impairment of physical and mental function. An earlier report from this study showed that almost twice as many patients randomized to the combination achieved disease remission, defined as a DAS28 <2.6.

DAS-guided Therapy and Drug-free Remission

Besides rapid onset of disease control, an update from the Behandel Strategieën (BeSt) study also showed that aggressive treatment of early RA with TNF inhibitor-based therapy offers patients the best chance for remission. Dr. Naomi Klarenbeek, Leiden University Medical Center, reported five-year data on the use of the DAS to implement and guide treatment aimed at tight disease control. Twoyear results from the study demonstrated the superiority of initial combination therapy over conventional approaches to RA treatment, and the five-year results showed those benefits were maintained. Dr. Klarenbeek reported that 1 in 5 patients treated with the methotrexate/infliximab combination achieved drug-free remission (DAS <1.6), the highest rate of the four treatment groups. Initial treatment with methotrexate/ infliximab also resulted in significantly better preservation of functional ability as reflected in HAQ score (P=0.01 to P<0.001 vs. all other groups). This combination also led to the least radiographic progression among the treatment groups.

Dr. Diane van der Woude, Leiden University Medical Center, reported results from a comparison of two strategies for treatment of early RA. Patients in the BeSt study had DASsteered therapy aimed at maintaining tight disease control, i.e. aiming for a DAS =2.4. The goal of therapy was drugfree remission, defined as a DAS <1.6 for at least a year after discontinuing all DMARDs. Results in the BeSt cohort were compared with data extracted from the records of patients treated conventionally at an early-RA clinic. The two strategies led to similar rates of sustained drug-free remission. However, high-risk patients (defined as CCP2- positive) were three times as likely to achieve sustained drug-free remission with DAS-guided therapy. Thus, patients who have poor-prognosis characteristics are more likely to achieve a sustained drug-free remission with DAS-guided therapy than with a conventional treatment approach.

The importance of identifying patients at high risk of rapid progression is key to initiating proper treatment. Co-investigator Dr. Nathan Vastesaeger, Leiden, The Netherlands, used data from a study of early RA to develop a risk matrix model for predicting rapid progression. The three most predictive factors were baseline swollen-joint count, C-reactive protein level, and rheumatoid factor positivity. Applying the matrix to data from a trial involving patients with methotrexate-refractory RA, he found that only three patients in the highest-risk category for the three markers would need to be treated with methotrexate/infliximab combination therapy to prevent one rapid progression on methotrexate monotherapy.

Persistency and Treatment Failure

Randomized trials of TNF inhibitors primarily involved biologicnaive patients. In clinical practice, switching from one anti-TNF agent to another is not uncommon. Dr. Jeffrey Greenberg, New York University, and colleagues compared response rates to anti-TNF therapy in biologic-naive and biologicexperienced patients (one or two switches). Not surprisingly, the best response rates occurred in the biologic-naive patients. Patients with no prior exposure to anti-TNF therapy also were significantly less likely to discontinue therapy. The study revealed differences in persistency with therapy among the anti-TNF agents. Biologic-naive patients had a significantly lower discontinuation rate with infliximab vs. adalimumab or etanercept (HR 0.74; 95% CI: 0.61-0.89).

TNF Inhibition Cost-Effectiveness

Data from the BeSt study provided the basis for a costeffectiveness analysis reported by Dr. Michael Ganz, Lexington, Massachusetts. The analysis examined the relative cost-effectiveness of initial treatment with the methotrexate/ infliximab combination vs. sequential DMARD therapy. The cumulative cost of initial combination therapy was higher, owing largely to higher cost in the first year of treatment. Over the course of five years, the methotrexate/infliximab combination led to greater improvement in quality-adjusted life-years (QALYs). During the first year of therapy, the cost per QALY was substantially higher with initial combination therapy. However, the cost declined substantially in year 2, and from year 3 to year 5, the cost per QALY was similar with the two strategies and roughly half the £30,000 standard for cost-effectiveness in the UK. Dr. Ganz and colleagues reported that the greater improvement with the combination offset the higher initial cost.

Increasing the Armamentarium

In many patients, RA remains active despite methotrexate. Dr. Edward Keystone, University of Toronto, Ontario, presented data from a randomized clinical trial of add-on therapy with the newest of the TNF inhibitors, golimumab. Patients who had inadequate disease control with methotrexate monotherapy were randomized to methotrexate plus placebo; golimumab 100 mg plus placebo; or to 50 or 100 mg golimumab plus methotrexate. The results showed that TNF inhibitor add-on to methotrexate significantly reduced signs and symptoms of RA and improved physical function through week 24, compared with methotrexate plus placebo. Golimumab plus placebo demonstrated numerical superiority over methotrexate plus placebo.

Summary

The evidence to treat RA early is undisputable. While one of the challenges remains that of earlier diagnosis, studies consistently showed that early treatment with combination therapy with a TNF-a inhibitor slows radiographic progression and leads to significantly greater improvements in physical function, fatigue and overall health state. The BeSt study has demonstrated the potential for drug-free remission, adding value to combination treatment with a TNF-a inhibitor.

ABSTRACT 2043 Window of Opportunity in Early Rheumatoid Arthritis. Combination Therapy with FIN-RACo Strategy During the First 2 Years Translates into Less Joint Erosions in 11-year Radiographs

V. Rantalaiho, L. Laasonen, H. Kautiainen, M. Korpela, P. Hannonen, M. Leirisalo-Repo, T. Möttönen

Purpose: To evaluate the radiological progression during 11 years in patients with early rheumatoid arthritis (RA) initially treated either with a combination of 3 DMARDs or a single DMARD.

Methods: A cohort of 195 patients with early RA were randomized to a treatment with a combination of methotrexate, sulfasalazine, hydroxychloroquine and prednisolone (COMBI) or with a single DMARD (initially sulfasalazine) with or without prednisolone (SINGLE). After 2 years, the drug treatments became free, but were still targeted to remission. The radiographs of hands and feet were analyzed using the Larsen score at baseline, 2, 5 and 11 years.

Results: Sixty-five COMBI [60% women, 72% RF+, mean(SD) age at baseline 46(9) years] and 65 SINGLE [71% women, 65% RF+, 48(10) years] patients had radiographs of hands and feet available at baseline and at 11 years. At baseline the median (IQR) Larsen score was 0 (0 , 2) in COMBI and 2 (0 , 8) in SINGLE. The median (IQR) Larsen scores at baseline, 2, 5 and 11 years in both groups are shown in Figure 1. The median change in Larsen score from baseline to 11 years was 12 (95% CI: 4 to 16) in COMBI and 20 (95% CI: 12 to 30) in SINGLE (p=0.039, adjusted for age, sex, RF presence and baseline Larsen score). No erosive changes were present at 11 years in 18% of COMBI and 6% of SINGLE patients (p=0.059).

Conclusions: In early RA, patients treated initially with a combination of DMARDs during the first 2 years have less radiological progression even in long term than those randomized to monotherapy.

Commentary on abstract 2043

This study examined radiographic progress at 11 years among patients with early RA who received multi-DMARD therapy or a single DMARD during the first two years. At that point, the randomized phase of the trial ended, and patients entered a long-term extension phase during which treatment could be modified, including the addition of adalimumab. At baseline, the combination group had a median Larsen score of 0, and patients initially treated with a single DMARD had a baseline median Larsen score of 2. At 11 years, patients randomized to the multi-DMARD combination as initial therapy had a mean change in Larsen score of 12, whereas patients started on a single DMARD had a mean change of 20. After adjustment for multiple baseline characteristics, the difference remained statistically significant in favour of multi-DMARD therapy (P=0.039). Additionally, three times as many patients started on multi-DMARD therapy had no erosive changes from baseline to year 11 (18% vs. 6%, P=0.059). The results confirmed previously reported findings from the two-year randomized phase. The data also provided additional confirmation of the value of aggressive treatment of early RA.

Questions and answers with Dr. Vappu Rantalaiho, Tampere University Hospital, Finland

Q: What is meant by the “window of opportunity” that was part of the title of your presentation?

A: RA begins to cause joint damage very early in the course of the disease. Clinicians must act early and aggressively if they hope to limit or prevent the damage and the disability associated with joint damage.

Q: What is the take-home message of this study?

A: Early, aggressive treatment—with multiple DMARDs in this case—leads to long-term benefits in the form of less radiographic progression.

ABSTRACT 1640 - Evaluation of Two Strategies (Initial Methotrexate Monotherapy Versus Its Combination with Adalimumab) in Management of Early Active Rheumatoid Arthritis During the First Year of Evolution: Data From the GUEPARD Trial

M. Soubrier, X. Puechal, J. Sibilia, X. Mariette, O. Meyer, B. Combe, R. M. Flipo, P. Goupille, F. Berenbaum, C. Zarnitsky, T. Schaeverbeke, P. Fardellone, M. Dougados

Background: MTX is the cornerstone therapy of early and active rheumatoid arthritis (RA). In cases of persistent active disease continuous treatment with TNF blockers is recommended in addition to MTX.

Objectives: To compare this strategy with an initial combination of MTX and Adalimumab (ADA) given for 3 months and then on demand.

Methods: 1-Study design: Prospective randomized multicenter controlled one-year trial (Clinical trials. gov#NCT00291915); 2-Patients: Early (< 6 months) and active (DAS28ESR > 5.1) RA; 3-Study drugs: Group1: MTX (0.3 mg/kg/w, maximum of 20 mg/kg/w, without escalating dose regimen) or Group 2: initial combination therapy with MTX (same regimen as in Group 1) and ADA (40 mg eow). In both groups, treatment was adjusted every 3 months. The aim was to achieve a low disease activity state (LDAS) (DAS28ESR < 3.2). 4-Analysis: The one year area under the curve (AUC) of DAS28ESR defined the primary endpoint.

Results: Of the 65 patients (80 % female, mean age 47.8 +/- 15.7 years, duration of symptoms 20 +/- 4.6 weeks), 32 and 33 were assigned to groups 1 and 2 respectively. All patients had active disease (DAS28 6.19), 34 % had erosive disease, 73.8% had RF and 73% anti-CCP. Eight patients dropped out (3 patients in group 1, and 5 in group 2). The one year AUC of DAS28 was lower in group 2 (164 vs 186 in group 1 p< 0.05) owing to an initial better response (AUC W0-W12 : 49 vs 62 p<0.0001). The percentage of patients in LDAS were, 25 vs 64 (p=0.001) at W12 and 65 vs 64 (p=0.98) at W52 in groups 1 vs 2 respectively. From W12 until W52, 7 patients in group 1 and 11 patients in group 2 remained in LDAS while receiving MTX monotherapy. The total consumption of anti-TNF agents was similar in the 2 groups. The mean increase in total modified Sharp score was 1.8 +/- 4.7 and 1.9 +/- 4 in groups 1 and 2, respectively. There were 16 patients without radiological progression in group 1 and 14 in group 2.

Conclusion: This study confirms the interest of a tight control of the disease and suggests that despite a faster response to therapy, an initial MTX-anti-TNF combination strategy did not achieve a better subsequent clinical or radiological outcome than a 3 month delayed initiation of anti-TNF in patients still active despite MTX therapy. Both strategies resulted in a similar one year dose of anti-TNF intake.

Commentary on abstract 1640

This trial represented another evaluation of anti-TNF combination therapy vs. monotherapy with methotrexate as the initial approach to treatment of early RA. In contrast to the BeSt trial, a DAS28 <3.2 was used to guide therapy, and remission was defined as DAS28 <2.6 for at least six months. Patients had multiple clinical assessments by hospital-based and private rheumatologists during a year of treatment and follow-up and completed the French version of the HAQ at baseline and every 12 weeks until the end of the study. Radiographic assessment occurred at baseline, week 24 and week 52. The primary end points were the area under the curve (AUC) of DAS28-ESR and the proportion of patients with low disease activity at week 12 and for whom anti-TNF therapy was not reintroduced. The results showed that initial combination therapy led to a more rapid response. However, delayed initiation of anti-TNF therapy with adalimumab after inadequate response to methotrexate monotherapy resulted in similar clinical and radiologic outcomes as compared to the strategy of initial combination therapy. Both strategies resulted in a similar anti-TNF intake at one year.

ABSTRACT 995 - Initial Combination Therapy with Adalimumab and Methotrexate Leads to Better Long-Term Inhibition of Radiographic Progression in Early RA: 5-Year Results of the PREMIER Trial

D. van der Heijde, R. Landewe, J. T. Sharp, E. C. Keystone, K. Patra, J. L. Perez, A. L. Pangan

Purpose: Previously reported results from the PREMIER study showed that the combination of adalimumab (ADA) and methotrexate (MTX) was significantly better at inhibiting radiographic progression at 2 years than either monotherapy in patients with early RA.1 In a long-term, open-label extension (OLE) of PREMIER, we evaluated the effects of ADA, with and without MTX, on sustained inhibition of radiographic progression through 5 years.

Methods: 799 patients with early RA (<3 yrs) received blinded treatment with ADA + MTX, ADA alone, or MTX alone for 2 years.1 All patients who had remained on blinded therapy were permitted to enroll in an OLE and receive ADA 40 mg every other week. Concomitant use of MTX any time during the OLE was at the investigators’ discretion. For patients who had reached 5 years of therapy, 5-year radiographs were evaluated by the modified total Sharp score (mTSS) method by 2 readers. Blinded to patients and sequence, these readers also re-assessed radiographs taken at baseline and 2 years. We assessed mean changes in mTSS based on patients’ original randomization arms.

Results: 360 patients had available ACR responses and radiographic scores at 5 years of therapy (126 originally randomized to ADA + MTX; 117 to ADA monotherapy; 117 to MTX monotherapy). The following numbers of patients had stable (=12 consecutive weeks), none, or some MTX use during Years 2-5: ADA + MTX (53, 71, 2); ADA (46, 68, 3); and MTX (55, 59, 3). Baseline disease characteristics for the ADA + MTX; ADA; and MTX groups were as follows (means): DAS28 (6.3, 6.3, 6.2), CRP (mg/dL) (4.0, 3.7, 3.6), and HAQ (1.4, 1.6, 1.5). Patients from the original combination therapy arm had a smaller mean change from baseline in mTSS at 5 years (2.8) vs. ADA alone (7.4) and MTX alone (9.2). Mean change in mTSS from baseline to Year 2 (blinded period) and Year 2-5 (OLE), and % of patients without radiographic pr
re provided (table).

<img2571|center>

Conclusion: For patients with early RA, initial ADA + MTX therapy for 2 years led to the best long-term inhibition of radiographic progression at 5 years. More than half of these patients had no radiographic progression at 5 years. Despite receiving open-label ADA, patients originally randomized to MTX experienced more radiographic progression from Years 2-5 than patients in either of the other 2 groups.

¹Breedveld et al. Arthritis Rheum 2006;54:26-37.

Commentary on abstract 995

This trial represented another examination of initial combination therapy with methotrexate and a TNF inhibitor, adalimumab in this case, in early RA. Consistent with results from other studies, the trial showed that beginning therapy with a TNF inhibitor-based combination leads to superior outcomes at five years compared with methotrexate alone or adalimumab alone as initial therapy. The initial treatment strategy continued for two years, at which time randomized therapy ended and patients switched to open-label adalimumab. Methotrexate could be restarted at physician discretion at any time during the open-label extension. Despite the fact that all patients received the same open-label therapy during years 3 to 5, those who began treatment with the adalimumab/methotrexate combination had less radiographic progression at five years. More than half (53%) of patients started with the combination had no radiographic progression at five years vs. 33 to 34% in the other two groups. The pattern continued to favour combination therapy in analyses that included no radiographic progression and clinical remission, defined as a DAS28 <2.6y (40% vs. 18%), and the most stringent criteria of no radiographic progression, clinical remission, and normal physical function, defined as a HAQ =0.5 (35% vs. 13-14%).

Questions and answers with Dr. Désirée van der Heijde, Leiden University Medical Center, The Netherlands

Q: Do you prescribe the combination of methotrexate and a TNF inhibitor as initial therapy for early RA? If so, how often do you prescribe the regimen?

A: I usually start with methotrexate in combination with prednisone for a short period, and if the patient does not respond sufficiently, I start a TNF-blocker.

Q: What is the tolerability of combination therapy as initial treatment for early RA?

A: The tolerability is very good.

Q: Do you think these results are applicable to other TNF inhibitors?

A: Probably, but the data have to show this.

ABSTRACT 781 - Assessment of Patient-Reported Outcomes from a Double-Blind Trial of Etanercept and Methotrexate Combination in Early Active Rheumatoid Arthritis: The COMET Trial

P. Durez, P. Emery, S. Hall, A. Koenig, R. Sato, A. Singh, D. Robertson, B. Freundlich

Purpose: To evaluate the impact of early treatment with ETN+MTX compared with MTX alone on PRO among patients with active RA.

Methods: COMET (Combination of Methotrexate and Etanercept in Active Early Rheumatoid Arthritis) is an on-going 24-month, double-blind, randomized, 2-period study. Patients were randomized at baseline to receive ETN+MTX (N=274) or MTX alone (N=268) for the initial 12 months. At baseline all patients were MTX-naïve. PROs assessed included: the Short Form-36 (SF-36) physical component summary (PCS) and mental component summary (MCS) scores [normalized general population mean equal to 50]); Fatigue VAS [range 0-100]; EuroQOL-5D (EQ-5D VAS [range 0-100]; and EQ-5D utility [range 0-1]). Mean changes from baseline in PRO measures for the modified intention-to-treat population were analyzed by analysis of covariance using last observation carried forward for missing data. Results from week 52 are presented.

Results: The patient population was predominately female (73.3%), had active disease at baseline (mean DAS28 of 6.5 ± 0.98 SD), mean age of 51.4 years (± 0.61 SE), and median disease duration of 7 months. Median MTX dosage was 19.6 mg/wk and 16.8 mg/wk in MTX and ETN+MTX groups, respectively. The two groups had similar baseline PRO scores with substantially impaired QOL (Table). All measures of PRO, with the exception of SF-36 MCS, showed significantly greater improvement with ETN+MTX treatment compared with MTX alone. The greatest improvements were found for the EQ-5D utility scores. At week 52, a significantly greater proportion of patients receiving ETN+MTX than those receiving only MTX achieved EQ-5D VAS within population norms (VAS>82) (39.8% vs 29.9%, p<0.05), and reported “no problem” in the EQ-5D dimension of Mobility (67.0% v 56.1%, p<0.05) and in Pain/Discomfort (31.8% v 20.1%, p<0.01).

Conclusions: Even in its early stages, RA significantly impairs physical and mental function and has a dramatic impact on fatigue and overall health state. Findings reported here demonstrate that early treatment with ETN+MTX led to significantly greater improvements in physical function, fatigue, and overall health state compared with MTX alone. Significant improvements
mplement the 50% clinical remission observed in the ETN+MTX group.

<img2577|center>

Commentary on abstract 781

Similar to other trials reported at the ACR meeting, investigators in this trial randomized patients to initial combination therapy with methotrexate and etanercept or to methotrexate alone. Treatment continued for a year. Patient-reported outcomes consisted of two assessments of the patient’s health status, a fatigue scale, and the Medical Outcomes Short Form (SF-36). By self-reported health status and the SF-36, the patients demonstrated the significant morbidity and impairment associated with early active RA. Both health status scales demonstrated significant improvement 12 weeks after beginning therapy, but the magnitude of improvement was significantly greater with combination therapy (P<0.05 to P<0.001 at all time points). Fatigue improved as early as two weeks after starting therapy and persisted out to week 52, with significantly greater improvement in patients started on combination therapy (P<0.05 to P<0.001). A similar pattern was observed for SF-36 results (P<0.01 to P<0.001). The improvements in health-related quality of life are in addition to a 50% remission rate (DAS28 <2.6) with combination therapy (vs. 28% with methotrexate alone) previously reported by the same group.

Questions and answers with Dr. Patrick Durez, Catholic University Louvain, Brussels, Belgium

Q: How often do you prescribe the combination of methotrexate and a TNF inhibitor for patients with early RA?

A: We use the combination MTX and TNF blockers for the majority of our patients. Monotherapy is allowed in case of remission or intolerance.

Q: How have you found the tolerability of methotrexate/TNF inhibitor combination therapy?

A: The combination in early RA is very well tolerated.

Q: Do you think these results represent a class effect of TNF inhibitors?

A: I suppose that these results might be extrapolated to all TNF blockers.

ABSTRACT 1996 - Clinical and Radiological Outcomes in Recent Onset Rheumatoid Arthritis after 5 Years of DAS-steered Treatment in the BeSt-Study

N. B. Klarenbeek, M. Güler-Yüksel, S. M. van der Kooij, D. M. F. M. van der Heijde, K. H. Han, H. M. J. Hulsmans, P. J. S. M. Kerstens, I. Speyer, T. W. J. Huizinga, B. A. C. Dijkmans, C. F. Allaart

Purpose: To compare the outcomes of four treatment strategies in recent onset rheumatoid arthritis patients after 5 years of DAS-steered therapy.

Methods: 508 patients were randomized into 4 therapy strategies: 1. sequential monotherapy (n=126); 2. step-up combination therapy (n=121); 3. initial combination with prednisone (n=133); 4. initial combination with infliximab (IFX, n=128). Threemonthly therapy adjustments were made aiming at DAS <= 2.4. Primary endpoints were functional ability (HAQ) and joint damage progression (Sharp-van der Heijde Score, SHS).

Results: Baseline characteristics were comparable between the groups. During 5 years of DAS-steered treatment, the initial functional improvement of year 1 was maintained in all groups (mean ? HAQ year 1-5 = -0.04). On average, patients in group 4 had the lowest HAQ scores over time, although the majority of these patients discontinued IFX (table). At t=5 years, 14, 16, 10 and 19% of patients in group 1-4 were in drug-free remission (mean duration 22 months). Group 3 and 4 had an earlier clinical response in year 1 and still showed significantly less joint damage progression at t=5 years compared to group 1 and 2. In all groups, annual progression (median) was the highest in year 1 (2.0 (mean 3.4) and lower in subsequent years (0, 0.75, 0.75, 0.50 for year 2-5 (means: 1.5, 1.1, 1.4, 1.6)) reflecting the efficacy of DAS-steered therapy. In each year of follow-up, more patients in group 1 and 2 showed progression of >= 5 SHS units than in group 3 and 4 (survival analysis; p<0.01: group 4 vs group 1 and 2; p=0.05 and p=0.10: group 3 vs group 1 and 2). Similar results were seen for progression >1, >10 or >20 SHS units. SHS progression remained low (mean 0.34 per year) after patients achieved sustained drug-free remission (n=32). Of these patients, 24 had no SHS increase and the highest SHS progression was 5 units (n=1). Toxicity in the 4 groups was comparable.

Conclusions: Joint damage progression remains adequately suppressed and functional improvement is sustained with DAS-steered treatment in recent onset RA patients, regardless of treatment strategy. After 5 years, patients initially treated with combination therapy still have the benefit with significantly less joint damage, and, after initial i
er HAQ scores. Ten to 19% of patients achieve drug-free remission and rarely suffer joint damage progression.

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Commentary on abstract 1996

The Dutch Behandel Strategieën (BeSt) study addressed three key issues related to optimal treatment of early-onset RA: monotherapy vs. combination therapy; the position of anti-TNF agents in the treatment algorithm; and the value of tight disease control. Five-year follow-up data from this trial went a long way toward answering the questions. Initial combination methotrexate/infliximab treatment led to the highest rate of drug-free remission (DAS <1.6), 19% vs. 10-16%, and to the largest proportion of patients who had drug-free remission for more than a year (mean duration 22 months). Initial treatment with this combination also resulted in significantly better preservation of functional ability as reflected in HAQ score (P=0.01 to P<0.001 vs. all other groups). The rate of radiologic progression was similar to that of the group that received prednisone-containing triple-drug therapy as initial treatment and significantly better than sequential monotherapy and step-up combination therapy (P=0.04).

Questions and answers with Dr. Naomi Klarenbeek, Leiden University Medical Center, The Netherlands

Q: Can you comment on the criteria used to guide therapy in the BeSt study?

A: We used very strict criteria, defined as a DAS <1.6. We feel this level of disease control gives patients the best chance to achieve disease remission.

Q: What was the tolerability of the initial combination therapy?

A: The treatment regimens were generally well tolerated, and the rate of adverse events was similar in the four treatment groups. Initial combination treatment with infliximab and methotrexate was associated with the lowest discontinuation rate due to adverse events, and was significantly lower compared with step-up combination therapy.

Q: Did initial combination therapy with methotrexate and infliximab distinguish itself in any way from the other treatment arms?

A: The combination led to the highest rate of drug-free remission and was associated with less radiographic progression and significantly better function as reflected in HAQ scores.

ABSTRACT 2046 - Improved Outcomes of Drug-free Remission with DAS-steered Therapy Compared to Conventional Therapy for Rheumatoid Arthritis

D. van der Woude, K. Visser, R. Brand, N. B. Klarenbeek, M. P. M. van der Linden, C. Mallée, W. M. de Beus, P. J. S. M. Kerstens, B. A. C. Dijkmans, T. W. J. Huizinga, A. H. M. van der Helm-van Mil, C. F. Allaart

Purpose: To compare drug-free remission in rheumatoid arthritis (RA) patients after conventional therapy and after DAS-steered therapy.

Methods: Sustained drug-free remission was assessed in two cohorts of patients with recent onset RA: in the Leiden Early Arthritis Cohort 410 patients were treated with conventional therapy, whereas in the BeSt trial, 508 patients received DAS-steered treatment, aiming at DAS=<2.4. Baseline characteristics of patients who after 5 years of follow-up had and had not achieved sustained drug-free remission (defined as DAS<1.6 for at least 1 year after discontinuing all DMARDs) were compared by univariate and multivariate logistic regression analysis within each cohort. In a combined multivariate logistic regression analysis correcting for baseline cohort characteristics, differences in the effects of the identified predictors for sustained drugfree remission between the two cohorts were analyzed using interaction terms. Radiographic damage in Sharp/van der Heijde scores (SHS) and functional ability by health assessment questionnaire (HAQ) at the time of remission were compared in a multivariate linear regression analysis corrected for baseline SHS and HAQ scores and cohort differences.

Results: At baseline, RA patients in the DAS-steered cohort had longer symptom duration and more active disease than patients in the conventional cohort. Sustained drug-free remission was achieved by 45/410 (11%) patients in the conventional cohort and by 48/508 (9%) patients in the DAS-steered cohort. In the conventional cohort, independent predictors for sustained drug-free remission were a low CRP (OR 1.02, 95%CI 1.00-1.03) and absence of anti-cyclic citrullinated peptide antibodies (ACPA) (OR 12.4, 95%CI 4.7-33), whereas in the DAS-steered cohort male gender (OR 3.0, 95%CI 1.5-6.1), low tender joint count (OR 1.07, 95%CI 1.01-1.13) and absence of ACPA (OR 5.9, 95%CI 2.8-12.1) were independent predictors. The effect of ACPA on sustained drug-free remission was three times less strong in the DAS-steered cohort compared to the conventional cohort (OR 0.34, 95%CI 0.1-1.1, p=0.07). DAS-steered treatment was an independent predictor for lower SHS (median 2.0 (0-7.5) versus 5.0 (0-11)) and lower HAQ scores (median 0 (0-0.25) versus 0.25 (0-0.94)) at the time of remission.

Conclusions: DAS-steered therapy induces sustained drug-free remission in RA patients with unfavorable prognostic characteristics and results in less radiographic damage and better functional ability at the time of drug free remission compared with conventional therapy.

Commentary on abstract 2046

This trial compared tight control of RA disease activity and conventional treatment with respect to attainment of disease remission. To evaluate the efficacy of tight control, investigators turned to the BeSt database and the use of DAS guided therapy. Remission was defined as a DAS <1.6, the standard used in the BeSt study. Sustained drug-free remission was defined as a DAS <1.6 for more than one year. The performance of conventional therapy was based on data from an early-arthritis clinic in Leiden, The Netherlands. The two treatment strategies yielded similar rates of sustained drug-free remission (~10%). Multivariate analysis of combined data from both cohorts revealed the presence of CCP2 antibodies as the strongest predictor of sustained drug-free remission, conferring an adverse likelihood of <10% (P<0.001). In that group of high-risk CCP2-positive patients, adherence to DAS-guided therapy with infliximab-based combination tripled the chances of sustained remission (OR 2.96).

Questions and answers with Dr. Diane van der Woude, Leiden University Medical Center, The Netherlands

Q: Given that the rate of drug-free remission was similar in the treatment groups, what did DAS steered therapy accomplish?

A: The study showed that drug-free remission is possible with DAS-guided therapy. The study also showed that DAS-guided therapy is more likely than conventional approaches to treatment to achieve sustained drugfree remission in patients who have poor-prognosis characteristics, especially the presence of anti-CCP2 antibodies.

Q: Did you identify any factors other than CCP2 status that predicted the likelihood of drug-free remission?

A: CCP2 status was the strongest negative predictor, followed by female gender, elevated CRP level, and increased duration of RA symptoms. The use of DAS-guided therapy, particularly in CCP2-positive patients, improved the likelihood of achieving drug-free remission.

ABSTRACT 1596 - Matrix Risk Model for Prediction of Rapid Radiographic Progression in Rheumatoid Arthritis

N. Vastesaeger, S. Xu, D. Aletaha, E. W. St. Clair, J. Smolen

Purpose: Identifying patients with rheumatoid arthritis (RA) at high risk for rapid radiographic progression (RRP) is critical to making appropriate treatment decisions. An exploratory prediction model was developed using an RA study population administered methotrexate monotherapy (MTX) or methotrexate in combination with infliximab (MTX+IFX).

Methods: Using data from the ASPIRE early-RA study, RRP was defined as a threshold change in modified Sharp/van der Heijde score (SHS) of =5 units/yr. Spearman’s rank analysis was used to identify baseline predictors and logistic regression was used to calculate the probability of RRP. The resulting algorithm generated a model based on ASPIRE data to predict the risk of RRP in a visual matrix comprised of baseline predictors and initiated treatment arranged in order of increasing probability. To test the applicability of the model, it was applied to the ATTRACT established-RA study.

Results: 28-swollen joint count, rheumatoid factor (RF), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) are included as trichotomous variables; treatment (monotherapy or combination therapy) as a dichotomous variable. A model incorporating all predictors except ESR was developed in a DMARD naïve RA population (ASPIRE, A) and tested in patients with longstanding MTX refractory RA (ATTRACT, B). Due to collinearity, ESR and CRP yielded similar results (ESR not shown). Using actual study results, the number in each cell of the matrix represents the predicted percentage of patients who will rapidly progress among a sub-population with similar baseline characteristics and intended treatment. For example, a DMARD naïve RA patient who has 18 swollen joints, 7 mg/dL CRP and 380 U/dL RF would have a 47% probability of RRP if treated with MTX or a 14% probability if treated with MTX+IFX. An MTX refractory patient with similar disease activity would have a 58% probability of RRP with MTX, and 22% if IFX was added to MTX. From ASPIRE, the NNT with MTX+IFX to prevent one patient to rapidly progress when treated with MTX was 3 for those within the highest ranges for CRP, SJC, and RF and 33 for those within the lowest ranges.

Conclusions: These matrix models predict the risk of RRP using treatment and easily accessible clinical and laboratory variables. Further explora
ation in other populations and with other therapies is needed to obtain a definitive risk model that can guide rheumatologists in making treatment decisions.

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Commentary on abstract 1596

The ability to identify patients with RA at high risk of rapid radiologic progression would give clinicians a powerful tool for use in clinical decision-making. Using data from the ASPIRE early-RA study, investigators defined rapid radiologic progression as a threshold change in modified Sharp/van der Heijde score (SHS) of =5 units/year. They then used Spearman’s rank analysis and logistic regression to identify baseline characteristics most closely associated with rapid progression. The resulting algorithm led a predictive model that included 28-swollen joint count, rheumatoid factor (RF) status, and C-reactive protein (CRP) value. Investigators applied the model to data from the ATTRACT trial involving patients with longstanding, methotrexate-refractory RA. Within the highest range of values for swollen-joint count, CRP and RF, only three patients need to be treated with initial methotrexate/infliximab combination therapy to prevent one rapid progression with methotrexate monotherapy. At the opposite end of the risk spectrum, 33 patients need to be treated to prevent one rapid progression among patients with the lowest range of predictive baseline characteristics.

Questions and answers with Dr. Nathan Vastesaeger, Leiden, The Netherlands

Q: Is the use of a matrix risk model to predict rapid progression of RA feasible for use in routine clinical practice?

A: Yes, I think so. The model is based on easily accessible clinical and laboratory variables.

Q: Is the model ready for use?

A: This was a preliminary evaluation. The model requires testing and validation in other patient populations and with other therapies to ensure that we have a definitive model that clinicians can use as an aid to clinical decision-making.

ABSTRACT 971 - Effectiveness of TNF Inhibitors (TNF-I) in Biologic Naïve and Switched RA Patients in a U.S. Cohort

J. Greenberg, A. Gibofsky, G. Reed, D. Decktor, R. DeHoratius, J. Kremer

Purpose: To compare persistency, response and remission rates to TNF-I for biologic naïve vs first-time (1st) switched and second-time (2nd) switched RA pts.

Methods: RA pts in the CORRONA registry prescribed a TNF-I with =1 follow-up were stratified into 3 cohorts: Naive pts (N=1,395), 1st switched pts (N=630) and 2nd switched pts (N=163). Demographics, disease activity variables and DMARDs including TNF-Is were analyzed. Persistency was compared using Cox regression expressed as Hazard Ratios (HR). Response was defined using modified (m) ACR20, and remission as Clinical Disease Activity Index (CDAI) <2.8. Differences in response and remission were calculated as odds ratios (OR) adjusting for baseline covariates. Outcomes for infliximab (INF) vs other TNF-I (adalimumab or etanercept) were limited to naïve and 1st switched pts due to sample size. Pts in CDAI remission at baseline (N=162) and who discontinued TNF-I due to toxicity (N=110) were excluded from analysis.

Results:

Persistency: Rates of persistency for naïve pts were 80.2% (6 mos), 67.5% (12 mos) and 52.8% (24 mos). Compared to naive pts, the HR for discontinuation was 1.43 (95% CI 1.25-1.63) for 1st-switched and 1.42 (95% CI 1.14-1.76) for 2nd-switched pts. No differences were observed between 1st and 2nd switched pts. The HR for discontinuation was significantly lower for INF vs other anti-TNFs (HR 0.74, 95% CI 0.61-0.89) in naïve pts, but not 1st-switched pts.

Response: mACR20 rates for naïve pts were 29.7% (6 mos), 26.9% (12 mos) and 23.0 (24 mos). Compared to naïve pts, 1st switched pts had lower mACR20 at 6 mos (OR 0.58, 95% CI 0.41-0.81), 12 mos (OR 0.50, 95% CI 0.33-0.75) and 24 mos (OR 0.51, 95% CI 0.30-0.87). No significant difference was observed for INF vs other TNF-I. Compared to naïve pts, 2nd switched pts had lower mACR20 at 6 mos (OR 0.41, 95% CI 0.22-0.76); results at 12 mos: OR 0.57, 95% CI 0.29-1.12 and 24 mos: OR 0.50, 95% CI 0.21-1.20. No differences were observed between 1st vs 2nd switched pts

Remission: For naïve pts, remission rates were 15.8% (6 mos), 15.0 (12 mos) and 15.5% (24 mos). Compared to naïve pts, 1st switched pts had lower remission rates at 6 mos (OR 0.46, 95% CI 0.28-0.76), 12 mos (OR 0.51, 95% CI 0.29-0.88) and 24 mos (OR 0.44, 95% CI 0.23-0.85). No significant difference was observed for INF vs other TNF-I. Compared to naïve pts, 2nd switched pts had lower remission rates at 6 mos (OR 0.20, 95% CI 0.05-0.82); results at 12 mos: OR 0.33, 95% CI 0.10-1.08 and 24 mos: OR 0.32, 95% CI 0.08-1.30. No differences were observed between 1st vs 2nd switched pts.

Conclusions:

1. Persistency, response and remission rates were consistently higher for naïve vs 1st-switched pts.

2. Higher persistency was observed for INF vs other TNF-I agents in naïve pts. No differences were found for INF vs other agents for other outcomes.

3. No differences of outcomes were observed for 1st vs 2nd TNF-I switched pts.

Commentary on abstract 971

Randomized clinical trials that demonstrated the efficacy of TNF inhibitors involved mostly biologic-naive patients with no prior exposure to anti-TNF therapy. Intraclass switching has been proposed as a therapeutic strategy for patients whose initial treatment fails or whose response wanes over time. However, outcomes with such a switching strategy had not been adequately examined. Using data from a registry of patients with inflammatory arthritis treated with a TNF inhibitor, investigators evaluated outcomes for biologic-naive patients, those switching from one TNF inhibitor to another for the first time, and patients switching within the class a second time. Perhaps not surprisingly, the analysis showed that the likelihood of achieving an ACR response was highest among biologic-naive patients and lowest among those switched for a second time. Moreover, persistency (time to discontinuation) was longer in patients with no prior exposure to anti-TNF therapy. The analysis also demonstrated significant differences among TNF inhibitors with respect to persistency. Specifically, biologic-naive patients were significantly less likely to discontinue infliximab compared with adalimumab (HR 1.42, P=0.004) and etanercept (HR 1.27, P=0.047).

Questions and answers with Dr. Jeffrey Greenberg, New York University, New York

Q: What do you consider to be the key message or messages of this analysis?

A: The study provides some data to support the concept of switching between agents in the TNF inhibitor class, which we know occurs with some regularity in clinical practice. The study also showed that biologic-naïve patients have the best responses and persistency with TNF inhibitors, which seemed intuitive but still needed to be evaluated. Finally, the study revealed differences among TNF inhibitors with respect to persistency with treatment, as biologic-naive patients were more likely to remain on infliximab than etanercept or adalimumab.

Q: Were the patients in this study comparable to those treated in clinical trials of TNF inhibitors?

A: No, these patients had lower disease activity scores at baseline. That is consistent with the growing emphasis on treating RA as early as possible to minimize or prevent joint damage and disability.

Q: Are these data applicable to switching patients from a TNF inhibitor to another biologic agent that is not in the same class?

A: That remains to be seen. That is a question for a study that is specifically designed to answer that question.

ABSTRACT 114 - Cost-Effectiveness of Initial Combination Therapy with Infliximab Versus Sequential DMARD Monotherapy, a Model Based on the BeSt Study

M. Ganz, M. Prasad, M. Russell, Y-C. Yeh

Purpose: Rheumatoid arthritis (RA) is a chronic autoimmune disease often causing joint destruction and disability. Treatment has evolved from symptomatic therapies to TNF-a inhibitors that limit disease progression. The clinical benefit of initial combination therapy with infliximab was established in BeSt, a randomized clinical trial assessing the impact of four treatment strategies in patients recently (less than 2 years) diagnosed with RA. Treatment options were sequential monotherapy with DMARDs (group 1), step-up combination therapy (group 2), initial combination therapy with tapered high-dose prednisone (group 3), and initial combination therapy with infliximab (group 4). This analysis evaluated the cost-effectiveness of initial combination therapy with infliximab vs. sequential DMARD monotherapy.

Methods: Data on clinical outcomes (Health Assessment Questionnaire [HAQ]) were extracted from the twoyear publication of BeSt. The model’s time horizon was five years; clinical findings were extrapolated using other literature. Medical resource use data and drug costs (2006 £) were obtained from the British National Formulary and two systematic NICE reviews of TNF-a inhibitors in RA. The base case represents the UK and a third-party payer perspective. The discount rate for cost and benefit is 3.5%. Model outcomes included cost per one-point improvement in HAQ and cost per quality-adjusted life-year (QALY). HAQ scores were translated into QALYs using formulas from NICE evaluations. One-way and probabilistic sensitivity analyses were conducted to determine the impact of drug cost, HAQ improvement, and the translation between HAQ and QALY.

Results: According to BeSt, initial combination therapy with prednisone or infliximab led to earlier HAQ improvement vs. sequential monotherapy and step-up combination therapy. Cumulative costs in group 1 increased from £1,155 to £15,875; costs in group 4 rose from £8,131 to £22,155. QALYs improved more in group 4 (0.70 to 3.30) than in group 1 (0.62 to 2.91). Initial combination therapy with infliximab is costeffective in later years: cost per QALY declines from £92,764 (year 1) to £15,965 (year 5) when this treatment strategy is compared with sequential monotherapy (figure). Results were not sensitive to changes in drug cost, HAQ, or the conversion a
ions: Higher costs associated with the earlier use of infliximab are offset by this regimen’s clinical benefit over time. Also, delaying the use of infliximab likely leads to costly structural damage.

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Commentary on abstract 114

The higher cost of TNF inhibitors compared with older, nonbiologic disease-modifying RA drugs has led to questions related to cost-effectiveness. This analysis compared costs associated with infliximab-based combination therapy vs. sequential monotherapy with DMARDs as the initial approach to treatment of early RA. Using data from the BeSt study, investigators compared two-year results on the HAQ. Primary outcomes were the cost per 1-point improvement in HAQ and cost per QALY. The analysis showed that infliximab combination therapy led to greater improvement in QALYs and that the cost per QALY decreased over time relative to sequential monotherapy. The cost per QALY with infliximab combination therapy was approximately $182,000 (CAD) during the first year of treatment, declining sharply beginning in the second year, and reaching a cost of about $31,000 in the fifth year. The results mean that the higher cost associated with early use of infliximab-based combination therapy is offset by greater and sustained improvement over time.

ABSTRACT 1211 - Golimumab Administered Subcutaneously Every 4 Wks in Patients with Active Rheumatoid Arthritis Despite Methotrexate: Wk 24 Results of the Randomized, Double-Blind, Placebo-Controlled, GO-FORWARD Study

E. Keystone, M. C. Genovese, L. Klareskog, E. C. Hsia, J. Livingston, M. Wiekowski, S. T. Hall, P. Miranda, J. Pazdur, S. C. Bae, W. Palmer, Z. Wu, M. U. Rahman

Purpose: To assess the efficacy and safety of golimumab (GLM) in patients (pts) with active RA despite methotrexate (MTX).

Methods: In this multicenter, randomized, DB, placebo (PBO)-controlled study, adult pts with active RA (=4 tender & 4 swollen joints) despite MTX were randomized (3:3:2:2 ratio) to PBO injections + MTX, GLM 100 mg injections + PBO capsules, GLM 50 mg injections + MTX, or GLM 100 mg injections + MTX. Injections were administered q4 wks. Coprimary endpts were the proportion of pts achieving ACR 20 at wk 14 and improvement from baseline (BL) in HAQ at wk 24. Data through wk 24 are presented.

Results: 444 pts with active RA were enrolled. Treatment groups were balanced for BL demographic and disease characteristics. GLM + MTX was significantly better than PBO + MTX in improving signs and symptoms of RA, as well as in improving physical function (Table). The 2 GLM doses + MTX were comparable in efficacy. While the GLM alone group had numerically better efficacy parameters than MTX alone, they generally did not reach statistical significance. GLM was generally well-tolerated. Through wk 16, the proportions of patients who had >1 adverse event was 60.9%, 63.2%, 68.5%, and 69.7% in the PBO + MTX, GLM 100 mg + PBO, GLM 50 mg + MTX, and GLM 100 mg + MTX, respectively. Serious adverse events occurred in 2.3%, 3.8%, 5.6%, and 9.0% of pts, respectively. Serious infections occurred in 0.8%, 2.3%, 2.2%, and 5.6% of pts, respectively. Injection site reactions occurred in 0.0%, 5.3%, 3.4%, and 4.5% of pts, respectively. One patient in the GLM 100 mg alone group died due
and sepsis. Three pts had malignancies: 1 breast cancer (GLM 100mg + MTX), 1 Bowen’s disease and squamous cell skin cancer (GLM 100 mg + PBO), and 1 basal cell carcinoma (PBO + MTX). There were no reports of tuberculosis or opportunistic infections.

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Conclusions: In patients with active RA despite MTX, the addition of GLM 50 mg or 100 mg SC injections q4 wks to MTX significantly reduced the signs and symptoms of RA and improved physical function through wk 24. GLM was generally well-tolerated.

Commentary on abstract 1211

The newest member of the anti-TNF class of agents, golimumab, continued the demonstration of superiority for TNF inhibitor-containing combination therapy vs. methotrexate monotherapy. The trial involved 444 patients with active RA despite treatment with methotrexate. Patients were randomized to four treatment groups: methotrexate alone, golimumab 100 mg alone, or golimumab 50 mg or 100 mg plus methotrexate. As early as 14 weeks, patients treated with either golimumab combination demonstrated significantly greater improvement vs. methotrexate alone in ACR response (20, 50 and 70), HAQ, DAS28 response and remission. The improvement was maintained out to 24 weeks. More than half of patients treated with the golimumab combinations had achieved an ACR20 response by week 24 vs. a third of methotrexate/placebo patients (P<0.001). Golimumab monotherapy also demonstrated a trend toward superiority over methotrexate alone (44.4%, P=0.059). At 24 weeks, almost 60% of patients randomized to the two TNF inhibitor combinations met criteria for an ACR20 response (59.6% vs. 27.8% for methotrexate alone, P<0.001). Additionally, three-fourths of combination patients had a good or moderate DAS response at week 24 vs. 42% for methotrexate monotherapy (P<0.001), and 21 to 22% of the combination groups achieved DAS28 remission vs. 6% of the methotrexate monotherapy group. Rates of adverse events did not differ among treatment groups.

Questions and answers with Dr. Edward Keystone, University of Toronto, Ontario

Q: Does golimumab have any advantages over other TNF inhibitors?

A: The most obvious advantage is convenience. It is administered once a month, compared with weekly or biweekly with the other agents in the class.

Q: What is its tolerability?

A: It has a safety profile similar to that of other anti-TNF agents.

Q: How did the different golimumab regimens compare with each other and with methotrexate alone?

A: The 50-mg or 100-mg dose of golimumab combined with methotrexate was superior to methotrexate alone. The two combinations were comparable to each other. Golimumab as a single agent generally was no better than methotrexate alone.