- Email: [email protected]
Hot rheumatology updates: January to March 2011
Indian Journal of Rheumatology 2011 March Volume 6, Number 1; pp. 46–49
Rheumservice
Hot rheumatology updates: January to March 2011 Sukhbir Uppal
RHEUMATOID ARTHRITIS Current smoking, female sex, longer symptom duration and younger age predict a worse response to MTX in patients with new-onset (< 1 year) DMARD naïve RA An extended report of the SWEFOT trial has found that current smoking, female sex, longer symptom duration and younger age predict a worse response to MTX in patients with new-onset (< 1 year) DMARD naïve RA. In this trial, after 3–4 months of MTX treatment, the frequency of EULAR good/moderate/no response was calculated. Parameters associated with a decreased likelihood of EULAR response were found to be female gender (adj OR 0.50), symptom duration (adj OR per month increase 0.93–0.99), current smoking (adj OR 0.35 to 0.63) and higher HAQ (adj OR 0.56 to 0.80). (ARD 2011; 70: 469–75). Male smokers with peptidyl arginine deiminase 4 (PADI4) gene are highly predisposed to RA Although it is well established that HLA-DRB1 region is the major genetic determinant of RA susceptibility, recent studies have revealed other non-HLA susceptibility genes for RA. Among these, the peptidyl arginine deiminase 4 (PADI4) gene, which encodes a post-translational modification enzyme that converts arginine to citrulline residues in proteins, is thought to have significant relevance in RA pathogenesis as anticitrullinated protein antibodies (ACPA). Male smokers with this particular polymorphism of PADI gene are highly predisposed to RA. The association carries a greater risk in men than women and in ever-smokers than never-smokers, and is greatest in male ever-smokers. This finding might partly explain the differing incidence of rheumatoid arthritis between populations, where smoking prevalence among males differs. (ARD 2011; 70: 512–5) The increased risk of RA due to smoking is dependent on the amount of smoking in individuals with the shared epitope HLA-DRB1 A case-control study encompassing 1204 patients with RA and 871 controls has found that in individuals carrying two
copies of the HLA-DRB1 SE, 55% of ACPA positive RA is attributable to smoking. Furthermore, the increased risk due to smoking is dependent on the amount of smoking in individuals with this particular genotype. (ARD 2011; 70: 508–11) Methotrexate is more effective and safer than leflunomide for long-term treatment of RA, especially in the setting of low socioeconomic RA patients It is well known that both leflunomide and methotrexate are effective drugs for the long-term treatment of RA. But which is more effective and safer, especially in the setting of low socio-economic RA patients? To answer this important question a double blind randomized clinical trial was carried out. Of 240 subjects who were randomized and treated, 129 received leflunomide and 111 received methotrexate, and the duration was 1 year. RA activity was clinically assessed by noting changes in the four primary (tender joint count, swollen joint count, physician and patient global assessment score) and three secondary (morning stiffness, pain intensity, HAQ) clinical efficacy end-points. The study found that the difference between baseline and 12 month end-point measurements of all primary clinical efficacy end-points was significantly greater in methotrexatetreated than leflunomide-treated subjects, whereas both leflunomide and methotrexate resulted in significant improvements in all secondary clinical efficacy end-points after 1 year of treatment. It was concluded that methotrexate, which is a much cheaper drug than leflunomide, is the drug of choice, especially for patients who belong to low socioeconomic groups. (Mod Rheumatol 2011) Sustained DAS28 remission in early RA patients can be achieved with a treatment to target approach even with conventional DMARDs Long-term remission with conventional DMARDs is a realistic goal in early RA patients in clinical practice, as shown by the excellent 2 year results in the so called DREAM remission inducton trial which used a “treatment to target approach”. In this study, more than 700 newly diagnosed patients with early RA (symptom duration ≤ 1 year) were
Consultant in Rheumatology, University Hospital Sharjah, and Professor of Medicine, Sharjah University College of Medicine, UAE. Correspondence: Dr. Sukhbir Uppal, email: [email protected]
Hot rheumatology updates: January to March 2011
enrolled in the cohort. Treatment adjustments (4–8 weekly) were based on the DAS28, aiming at DAS28 < 2.6 (initial MTX, addition of SSZ, exchange of SSZ by anti-TNF in case of persistent high disease activity). In 60% of patients sustained DAS28 remission (> 6 months) was observed during the first 2 years of follow-up. The majority of patients achieved remission on conventional DMARDs. (Excellence in Rheumatology Meeting in Istanbul, Turkey, February 2011) Discontinuation of TNF inhibitors is possible in 55% of patients with RA after achieving low disease activity score without progression of radiological articular destruction TNF inhibitors enable tight control of disease activity in patients with RA. Discontinuation of TNF inhibitors after acquisition of low disease activity (LDA) is important for safety and economic reasons. A study on 114 patients with RA who had received infliximab treatment, and whose Disease Activity Score was < 3.2 (LDA) for 24 weeks, concluded that after attaining LDA by infliximab, 55% of the 102 patients were able to discontinue infliximab for > 1 year without progression of radiological articular destruction. The mean modified total Sharp score (mTSS) was 63.3 at baseline. Yearly progression of mTSS (⌬TSS) was < 0.5 in 67% and 44% of the RRR-achieved and RRR-failed groups, respectively. The estimated ⌬mTSS was 0.3 and 1.6, respectively, in the 2 groups. (Ann Rheum Dis 2010; 69: 1286–9) Remission induction regime with an infliximab–MTX combination for 1 year in early RA can improve long-term clinical outcomes Twenty patients with poor prognosis RA of < 1 year of disease duration were randomized to receive either INF and MTX or placebo infusions and MTX for 1 year. They then stepped down to MTX monotherapy and were treated according to standard clinical care. After 8 years, disease activity, function and quality of life (QoL) data were collected. Median 28-joint DAS was significantly lower in the INF–MTX group compared with placebo–MTX group (2.7 vs. 4.3, P = 0.02). Four patients in the INF–MTX group were in remission vs. none in the placebo–MTX group. One patient in the INF–MTX group achieved drug-free remission. A remission induction regime with an INF–MTX combination for 1 year in early RA can improve long-term clinical outcomes. (Rheumatology 2010; 49: 1971–4) Halving RA patients’ etanercept doses after achieving remission cuts adverse effects and treatment costs dramatically without compromising the clinical effectiveness of maintenance therapy In a prospective, controlled study on 217 RA patients in remission for at least 1 year on etanercept 25 mg twice
Rheumservice
47
weekly, disease activity remained low in 81.6% of the 109 patients put on low-dose etanercept (25 mg once weekly) for a mean of 2.6 years after achieving remission on 25 mg twice weekly—virtually the same rate as in the 108 patients maintained without dose reduction. At the same time, infection rates were reduced significantly. Moreover, switching to a low-dose maintenance regimen reduced annual treatment costs by an average of €562,000 annually ($685,000) relative to the standard-dose regimen. Radiological arrest was maintained in 78% and 86% of the low-dose group with moderate and severe baseline disease activity, respectively. In the standard-dose maintenance group, the corresponding figures were 82% and 87%, respectively. The differences were not statistically significant. (EULAR 2010) It would be worth while replicating this study using etanercept 50 mg once weekly for remission induction, and 50 mg once every 2 weeks for remission maintenance. RA patients respond poorly to abatacept as the third line biologic The efficacy of abatacept as a third-line biologic is limited after failure of aTNF plus RTX. Thus, failure in response to aTNF and RTX identifies a difficult-to-treat RA population whose needs is currently not met and should become a focus of clinical trials. This was demonstrated by a longitudinal population-based cohort (The Swiss Clinical Quality Management (SCQM) programme for RA) which collected all the cases of RA with an inadequate response to at least one aTNF plus RTX, followed by abatacept. The 28 patients who met the inclusion criteria had an average of 6.3 assessments during a median follow-up of 22.1 months. All patients discontinued RTX because of insufficient disease control. The mean DAS-28 did not improve significantly over time (mean improvement at 6 months 0.38 DAS units, P = 0.48). Only six abatacept patients (21%) had a clinically meaningful DAS-28 improvement (0.6 units) after 6 months. (Rheumatology 2010) High titers of RF and anti-CCP occur in HIV infected persons with low CD4+ cell count. RF and anti-CCP do NOT predict onset of RA among these patients The second- and third-generation ELISA tests, anti-CCP2 and anti-CCP3, are known to be superior to RF for the diagnosis of RA. These provide an at least equal sensitivity (80%) with a superior specificity (94%–99%) compared to those of RF (80%–90%). However, a note of caution has been sounded in a study in the HIV setting: increased titers of anti-CCP and RF occur in advanced HIV infection. These high titers of RF and anti-CCP occur in HIV infected persons with low CD4+ cell count, before drug treatment. The levels fall and reach normal levels with drug treatment
48
Indian Journal of Rheumatology 2011 March; Vol. 6, No. 1
and correlate with the rise in CD4+ cell count. Thus, RF and anti-CCP do NOT predict onset of RA among these patients with advanced HIV infection and low CD4+ counts. (J Rheumatol First Release Feb 15 2011)
Uppal
acetonide caused ocular hypertension in four of the eight eyes, requiring surgical intervention in two. A single infusion of infliximab should always be considered, even as an adjunct therapy, for the control of acute panuveitis attacks in BD. (Rheumatology 2011; 50: 593–7)
BEHCET’S DISEASE SYSTEMIC LUPUS ERYTHEMATOSUS IFN-a induces long-lasting remission in patients with severe ocular BD, resulting in a notable improvement in visual prognosis Ocular involvement is frequent and occurs in ≥ 50% of patients with Behcet’s disease (BD). The most common ocular findings are a relapsing, mostly bilateral, posterior or panuveitis, often accompanied by a cystoid macular edema, and an occlusive retinal vasculitis. Without treatment, patients will become blind an average of 3.36 years after onset of the first symptoms. A study to retrospectively assess the visual acuity in 52 patients treated with interferon-α (6 million IU per day, then tapered to a maintenance dosage of 3 million IU twice per week, and finally discontinued, if possible) for severe uveitis due to BD found that at the end of a follow-up period of > 2 years 98.1% responded to IFN. In 47 patients IFN could be discontinued when the disease was in remission and 20 of these 47 needed a second treatment course. Visual acuity improved or remained unchanged in 94.8%. Ocular disease was still in remission. IFN-α induces long-lasting remission in patients with severe ocular BD, resulting in a notable improvement in visual prognosis. (A&R 2010; 62: 2796–805) A single infusion of infliximab is superior to corticosteroids in clearing retinal vasculitis secondary to Behcet’s disease A prospective, observational study of patients with panuveitis secondary to Behcet’s disease (BD), who received either an infliximab infusion (5 mg/kg, 19 eyes) or highdose methylprednisolone intravenously (1 g/day for 3 days, 8 eyes), or intra-vitreal triamcinolone acetonide (4 mg, 8 eyes) at attack’s onset and followed up for 30 days showed that while no significant differences were noted between i.v. and intra-vitreal CSs, infliximab was faster than CSs in decreasing total ocular inflammation scores and fundus inflammation scores (P = 0.01 and P < 0.0001, respectively). Independently of time, infliximab was superior to CSs in clearing retinal vasculitis (P < 0.003), as well as in resolution of retinitis (P = 0.008) and cystoid macular edema (P < 0.007). Moreover, a faster regression of cystoid macular edema was observed with infliximab compared with CSs (P < 0.03). No side effects were noted with infliximab or methylprednisolone, whereas intra-vitreal triamcinolone
Serum Albumin reflects disease activity in patients with SLE, especially in those with nephritis Do we have a new disease activity marker for SLE? A recent study looked at the relation between serum albumin level and SLE disease activity. Patients with ≥ 3 clinic visits within a maximum follow-up period of 10 years were selected from the University of Toronto Lupus Clinic database. A total of 1078 patients were studied. Serum albumin was more significantly associated with SLEDAI in Lupus nephritis. The association was also present but weaker in the non-nephritis group. In all lupus nephritis, the associations between serum albumin and SLEDAI-2K were stronger in those with proteinuria. In patients with SLE, higher SLEDAI was associated with lower serum albumin levels. (J Rheumatol 2010; 37: 1667–72) Epratuzumab, a monoclonal antibody against CD22 antigen on B-cells, is effective in SLE and could be combined with rituximab Epratuzumab is a monoclonal antibody that targets CD22 antigen on B-cells. Initial phase II and two terminated early phase III studies suggest that treatment of SLE with this immunomodulatory agent is effective, well tolerated and significantly improves the patient’s quality of life. In vitro studies and clinical trials with non-Hodgkin lymphoma patients indicate epratuzumab can potentially serve as a complementary drug in combination therapy with abother inhibitor of B-cell activity, rituximab, which is a monoclonal anti-CD20 antibody. (Brit J Clin Pharmacol 2011; 71: 175–82)
ANKYLOSING SPONDYLITIS Presence of pANCA is significantly increased in AS patients who also have ulcerative colitis, and is an indicator to perform endoscopy About 5%–10% of patients with AS have concurrent IBD, either Crohn’s disease (CD) or ulcerative colitis (UC). Antibodies associated with IBD are detectable in more than
Hot rheumatology updates: January to March 2011
half of AS patients without symptoms or signs of IBD. Arelatively recent marker in this setting, OmpC antibodies, does not contribute to the differentiation between AS and type of IBD. Presence of pANCA, however, is significantly increased in AS patients who also have UC, and is an indicator to perform endoscopy. A recent study on 179 patients (52 with AS, 50 with UC, 51 with CD, and 26 with IBD andAS) has investigated IBD serological markers in AS patients without IBD and whether these antibodies enable differentiating patients with AS and IBD from those without IBD. In 55% of the AS patients without manifest IBD at least one antibody associated with IBD was observed. pANCA, antiSaccharomyces cerevisiae antibodies “ASCA” (IgA and/or IgG), and OmpC antibodies were found in 21%, 30%, and 19% of the AS patients, respectively. pANCA was more frequently present in AS with concurrent UC than in AS alone (OR 8.2, 95% CI 1.2–55.6), thus being an indicator for UC in AS patients. These results corroborate a pathophysiological link between AS and IBD. Therefore, use of serological markers associated with bowel disease to select AS patients at risk of IBD could be helpful to increase the likelihood of a positive diagnosis following an invasive procedure. (J Rheumatol September 1 2010; doi:10.3899/jrheum.100269)
Rheumservice
49
MUSCULOSKELETAL ULTRASOUND Sonographic needle guidance improves the performance, clinical outcomes, and cost-effectiveness of IA injections for inflammatory arthritis A recent study has shown that sonographic needle guidance improves the performance, clinical outcomes, and costeffectiveness of IA injections for inflammatory arthritis. In this study, joints with inflammatory arthritis (n = 244; 76% rheumatoid arthritis, 3% small joints, 51% intermediate, and 46% large) were randomized to injection by conventional palpation-guided anatomic injection (120 joints) or sonographic image-guided injection enhanced with a 1-handed reciprocating procedure device mechanical syringe (124 joints). Relative to conventional palpation-guided methods, sonographic guidance for injection of inflammatory arthritis resulted in an 81% reduction in injection pain (P < 0.001), 35% reduction in pain scores at outcome (P < 0.02), 38% increase in the responder rate (P < 0.003), 34% reduction in the non-responder rate (P < 0.003), 32% increase in therapeutic duration (P = 0.01), 8% reduction in cost/patient/year, and a 33% reduction in cost/responder/year for a hospital outpatient (P < 0.001). (J Rheumatol 2011; 38: 252–63)
Rheumservice
Hot rheumatology updates: January to March 2011 Sukhbir Uppal
RHEUMATOID ARTHRITIS Current smoking, female sex, longer symptom duration and younger age predict a worse response to MTX in patients with new-onset (< 1 year) DMARD naïve RA An extended report of the SWEFOT trial has found that current smoking, female sex, longer symptom duration and younger age predict a worse response to MTX in patients with new-onset (< 1 year) DMARD naïve RA. In this trial, after 3–4 months of MTX treatment, the frequency of EULAR good/moderate/no response was calculated. Parameters associated with a decreased likelihood of EULAR response were found to be female gender (adj OR 0.50), symptom duration (adj OR per month increase 0.93–0.99), current smoking (adj OR 0.35 to 0.63) and higher HAQ (adj OR 0.56 to 0.80). (ARD 2011; 70: 469–75). Male smokers with peptidyl arginine deiminase 4 (PADI4) gene are highly predisposed to RA Although it is well established that HLA-DRB1 region is the major genetic determinant of RA susceptibility, recent studies have revealed other non-HLA susceptibility genes for RA. Among these, the peptidyl arginine deiminase 4 (PADI4) gene, which encodes a post-translational modification enzyme that converts arginine to citrulline residues in proteins, is thought to have significant relevance in RA pathogenesis as anticitrullinated protein antibodies (ACPA). Male smokers with this particular polymorphism of PADI gene are highly predisposed to RA. The association carries a greater risk in men than women and in ever-smokers than never-smokers, and is greatest in male ever-smokers. This finding might partly explain the differing incidence of rheumatoid arthritis between populations, where smoking prevalence among males differs. (ARD 2011; 70: 512–5) The increased risk of RA due to smoking is dependent on the amount of smoking in individuals with the shared epitope HLA-DRB1 A case-control study encompassing 1204 patients with RA and 871 controls has found that in individuals carrying two
copies of the HLA-DRB1 SE, 55% of ACPA positive RA is attributable to smoking. Furthermore, the increased risk due to smoking is dependent on the amount of smoking in individuals with this particular genotype. (ARD 2011; 70: 508–11) Methotrexate is more effective and safer than leflunomide for long-term treatment of RA, especially in the setting of low socioeconomic RA patients It is well known that both leflunomide and methotrexate are effective drugs for the long-term treatment of RA. But which is more effective and safer, especially in the setting of low socio-economic RA patients? To answer this important question a double blind randomized clinical trial was carried out. Of 240 subjects who were randomized and treated, 129 received leflunomide and 111 received methotrexate, and the duration was 1 year. RA activity was clinically assessed by noting changes in the four primary (tender joint count, swollen joint count, physician and patient global assessment score) and three secondary (morning stiffness, pain intensity, HAQ) clinical efficacy end-points. The study found that the difference between baseline and 12 month end-point measurements of all primary clinical efficacy end-points was significantly greater in methotrexatetreated than leflunomide-treated subjects, whereas both leflunomide and methotrexate resulted in significant improvements in all secondary clinical efficacy end-points after 1 year of treatment. It was concluded that methotrexate, which is a much cheaper drug than leflunomide, is the drug of choice, especially for patients who belong to low socioeconomic groups. (Mod Rheumatol 2011) Sustained DAS28 remission in early RA patients can be achieved with a treatment to target approach even with conventional DMARDs Long-term remission with conventional DMARDs is a realistic goal in early RA patients in clinical practice, as shown by the excellent 2 year results in the so called DREAM remission inducton trial which used a “treatment to target approach”. In this study, more than 700 newly diagnosed patients with early RA (symptom duration ≤ 1 year) were
Consultant in Rheumatology, University Hospital Sharjah, and Professor of Medicine, Sharjah University College of Medicine, UAE. Correspondence: Dr. Sukhbir Uppal, email: [email protected]
Hot rheumatology updates: January to March 2011
enrolled in the cohort. Treatment adjustments (4–8 weekly) were based on the DAS28, aiming at DAS28 < 2.6 (initial MTX, addition of SSZ, exchange of SSZ by anti-TNF in case of persistent high disease activity). In 60% of patients sustained DAS28 remission (> 6 months) was observed during the first 2 years of follow-up. The majority of patients achieved remission on conventional DMARDs. (Excellence in Rheumatology Meeting in Istanbul, Turkey, February 2011) Discontinuation of TNF inhibitors is possible in 55% of patients with RA after achieving low disease activity score without progression of radiological articular destruction TNF inhibitors enable tight control of disease activity in patients with RA. Discontinuation of TNF inhibitors after acquisition of low disease activity (LDA) is important for safety and economic reasons. A study on 114 patients with RA who had received infliximab treatment, and whose Disease Activity Score was < 3.2 (LDA) for 24 weeks, concluded that after attaining LDA by infliximab, 55% of the 102 patients were able to discontinue infliximab for > 1 year without progression of radiological articular destruction. The mean modified total Sharp score (mTSS) was 63.3 at baseline. Yearly progression of mTSS (⌬TSS) was < 0.5 in 67% and 44% of the RRR-achieved and RRR-failed groups, respectively. The estimated ⌬mTSS was 0.3 and 1.6, respectively, in the 2 groups. (Ann Rheum Dis 2010; 69: 1286–9) Remission induction regime with an infliximab–MTX combination for 1 year in early RA can improve long-term clinical outcomes Twenty patients with poor prognosis RA of < 1 year of disease duration were randomized to receive either INF and MTX or placebo infusions and MTX for 1 year. They then stepped down to MTX monotherapy and were treated according to standard clinical care. After 8 years, disease activity, function and quality of life (QoL) data were collected. Median 28-joint DAS was significantly lower in the INF–MTX group compared with placebo–MTX group (2.7 vs. 4.3, P = 0.02). Four patients in the INF–MTX group were in remission vs. none in the placebo–MTX group. One patient in the INF–MTX group achieved drug-free remission. A remission induction regime with an INF–MTX combination for 1 year in early RA can improve long-term clinical outcomes. (Rheumatology 2010; 49: 1971–4) Halving RA patients’ etanercept doses after achieving remission cuts adverse effects and treatment costs dramatically without compromising the clinical effectiveness of maintenance therapy In a prospective, controlled study on 217 RA patients in remission for at least 1 year on etanercept 25 mg twice
Rheumservice
47
weekly, disease activity remained low in 81.6% of the 109 patients put on low-dose etanercept (25 mg once weekly) for a mean of 2.6 years after achieving remission on 25 mg twice weekly—virtually the same rate as in the 108 patients maintained without dose reduction. At the same time, infection rates were reduced significantly. Moreover, switching to a low-dose maintenance regimen reduced annual treatment costs by an average of €562,000 annually ($685,000) relative to the standard-dose regimen. Radiological arrest was maintained in 78% and 86% of the low-dose group with moderate and severe baseline disease activity, respectively. In the standard-dose maintenance group, the corresponding figures were 82% and 87%, respectively. The differences were not statistically significant. (EULAR 2010) It would be worth while replicating this study using etanercept 50 mg once weekly for remission induction, and 50 mg once every 2 weeks for remission maintenance. RA patients respond poorly to abatacept as the third line biologic The efficacy of abatacept as a third-line biologic is limited after failure of aTNF plus RTX. Thus, failure in response to aTNF and RTX identifies a difficult-to-treat RA population whose needs is currently not met and should become a focus of clinical trials. This was demonstrated by a longitudinal population-based cohort (The Swiss Clinical Quality Management (SCQM) programme for RA) which collected all the cases of RA with an inadequate response to at least one aTNF plus RTX, followed by abatacept. The 28 patients who met the inclusion criteria had an average of 6.3 assessments during a median follow-up of 22.1 months. All patients discontinued RTX because of insufficient disease control. The mean DAS-28 did not improve significantly over time (mean improvement at 6 months 0.38 DAS units, P = 0.48). Only six abatacept patients (21%) had a clinically meaningful DAS-28 improvement (0.6 units) after 6 months. (Rheumatology 2010) High titers of RF and anti-CCP occur in HIV infected persons with low CD4+ cell count. RF and anti-CCP do NOT predict onset of RA among these patients The second- and third-generation ELISA tests, anti-CCP2 and anti-CCP3, are known to be superior to RF for the diagnosis of RA. These provide an at least equal sensitivity (80%) with a superior specificity (94%–99%) compared to those of RF (80%–90%). However, a note of caution has been sounded in a study in the HIV setting: increased titers of anti-CCP and RF occur in advanced HIV infection. These high titers of RF and anti-CCP occur in HIV infected persons with low CD4+ cell count, before drug treatment. The levels fall and reach normal levels with drug treatment
48
Indian Journal of Rheumatology 2011 March; Vol. 6, No. 1
and correlate with the rise in CD4+ cell count. Thus, RF and anti-CCP do NOT predict onset of RA among these patients with advanced HIV infection and low CD4+ counts. (J Rheumatol First Release Feb 15 2011)
Uppal
acetonide caused ocular hypertension in four of the eight eyes, requiring surgical intervention in two. A single infusion of infliximab should always be considered, even as an adjunct therapy, for the control of acute panuveitis attacks in BD. (Rheumatology 2011; 50: 593–7)
BEHCET’S DISEASE SYSTEMIC LUPUS ERYTHEMATOSUS IFN-a induces long-lasting remission in patients with severe ocular BD, resulting in a notable improvement in visual prognosis Ocular involvement is frequent and occurs in ≥ 50% of patients with Behcet’s disease (BD). The most common ocular findings are a relapsing, mostly bilateral, posterior or panuveitis, often accompanied by a cystoid macular edema, and an occlusive retinal vasculitis. Without treatment, patients will become blind an average of 3.36 years after onset of the first symptoms. A study to retrospectively assess the visual acuity in 52 patients treated with interferon-α (6 million IU per day, then tapered to a maintenance dosage of 3 million IU twice per week, and finally discontinued, if possible) for severe uveitis due to BD found that at the end of a follow-up period of > 2 years 98.1% responded to IFN. In 47 patients IFN could be discontinued when the disease was in remission and 20 of these 47 needed a second treatment course. Visual acuity improved or remained unchanged in 94.8%. Ocular disease was still in remission. IFN-α induces long-lasting remission in patients with severe ocular BD, resulting in a notable improvement in visual prognosis. (A&R 2010; 62: 2796–805) A single infusion of infliximab is superior to corticosteroids in clearing retinal vasculitis secondary to Behcet’s disease A prospective, observational study of patients with panuveitis secondary to Behcet’s disease (BD), who received either an infliximab infusion (5 mg/kg, 19 eyes) or highdose methylprednisolone intravenously (1 g/day for 3 days, 8 eyes), or intra-vitreal triamcinolone acetonide (4 mg, 8 eyes) at attack’s onset and followed up for 30 days showed that while no significant differences were noted between i.v. and intra-vitreal CSs, infliximab was faster than CSs in decreasing total ocular inflammation scores and fundus inflammation scores (P = 0.01 and P < 0.0001, respectively). Independently of time, infliximab was superior to CSs in clearing retinal vasculitis (P < 0.003), as well as in resolution of retinitis (P = 0.008) and cystoid macular edema (P < 0.007). Moreover, a faster regression of cystoid macular edema was observed with infliximab compared with CSs (P < 0.03). No side effects were noted with infliximab or methylprednisolone, whereas intra-vitreal triamcinolone
Serum Albumin reflects disease activity in patients with SLE, especially in those with nephritis Do we have a new disease activity marker for SLE? A recent study looked at the relation between serum albumin level and SLE disease activity. Patients with ≥ 3 clinic visits within a maximum follow-up period of 10 years were selected from the University of Toronto Lupus Clinic database. A total of 1078 patients were studied. Serum albumin was more significantly associated with SLEDAI in Lupus nephritis. The association was also present but weaker in the non-nephritis group. In all lupus nephritis, the associations between serum albumin and SLEDAI-2K were stronger in those with proteinuria. In patients with SLE, higher SLEDAI was associated with lower serum albumin levels. (J Rheumatol 2010; 37: 1667–72) Epratuzumab, a monoclonal antibody against CD22 antigen on B-cells, is effective in SLE and could be combined with rituximab Epratuzumab is a monoclonal antibody that targets CD22 antigen on B-cells. Initial phase II and two terminated early phase III studies suggest that treatment of SLE with this immunomodulatory agent is effective, well tolerated and significantly improves the patient’s quality of life. In vitro studies and clinical trials with non-Hodgkin lymphoma patients indicate epratuzumab can potentially serve as a complementary drug in combination therapy with abother inhibitor of B-cell activity, rituximab, which is a monoclonal anti-CD20 antibody. (Brit J Clin Pharmacol 2011; 71: 175–82)
ANKYLOSING SPONDYLITIS Presence of pANCA is significantly increased in AS patients who also have ulcerative colitis, and is an indicator to perform endoscopy About 5%–10% of patients with AS have concurrent IBD, either Crohn’s disease (CD) or ulcerative colitis (UC). Antibodies associated with IBD are detectable in more than
Hot rheumatology updates: January to March 2011
half of AS patients without symptoms or signs of IBD. Arelatively recent marker in this setting, OmpC antibodies, does not contribute to the differentiation between AS and type of IBD. Presence of pANCA, however, is significantly increased in AS patients who also have UC, and is an indicator to perform endoscopy. A recent study on 179 patients (52 with AS, 50 with UC, 51 with CD, and 26 with IBD andAS) has investigated IBD serological markers in AS patients without IBD and whether these antibodies enable differentiating patients with AS and IBD from those without IBD. In 55% of the AS patients without manifest IBD at least one antibody associated with IBD was observed. pANCA, antiSaccharomyces cerevisiae antibodies “ASCA” (IgA and/or IgG), and OmpC antibodies were found in 21%, 30%, and 19% of the AS patients, respectively. pANCA was more frequently present in AS with concurrent UC than in AS alone (OR 8.2, 95% CI 1.2–55.6), thus being an indicator for UC in AS patients. These results corroborate a pathophysiological link between AS and IBD. Therefore, use of serological markers associated with bowel disease to select AS patients at risk of IBD could be helpful to increase the likelihood of a positive diagnosis following an invasive procedure. (J Rheumatol September 1 2010; doi:10.3899/jrheum.100269)
Rheumservice
49
MUSCULOSKELETAL ULTRASOUND Sonographic needle guidance improves the performance, clinical outcomes, and cost-effectiveness of IA injections for inflammatory arthritis A recent study has shown that sonographic needle guidance improves the performance, clinical outcomes, and costeffectiveness of IA injections for inflammatory arthritis. In this study, joints with inflammatory arthritis (n = 244; 76% rheumatoid arthritis, 3% small joints, 51% intermediate, and 46% large) were randomized to injection by conventional palpation-guided anatomic injection (120 joints) or sonographic image-guided injection enhanced with a 1-handed reciprocating procedure device mechanical syringe (124 joints). Relative to conventional palpation-guided methods, sonographic guidance for injection of inflammatory arthritis resulted in an 81% reduction in injection pain (P < 0.001), 35% reduction in pain scores at outcome (P < 0.02), 38% increase in the responder rate (P < 0.003), 34% reduction in the non-responder rate (P < 0.003), 32% increase in therapeutic duration (P = 0.01), 8% reduction in cost/patient/year, and a 33% reduction in cost/responder/year for a hospital outpatient (P < 0.001). (J Rheumatol 2011; 38: 252–63)