Olivier Brocq

Effect of discontinuing TNFα antagonist therapy in patients with remission of rheumatoid arthritis

OBJECTIVE The objective of this study was to determine the time to relapse after tumor necrosis factor alpha (TNFalpha) antagonist discontinuation in patients with remission of rheumatoid arthritis (RA). METHODS Among 304 patients taking TNFalpha antagonist therapy for RA, 21 achieved a remission and were taken off the TNFalpha antagonist. Remission was defined as DAS28<2.6 for at least 6 months without nonsteroidal inflammatory drugs or more than 5 mg of prednisone per day but with disease-modifying antirheumatic drug (DMARD) therapy if needed. The same TNFalpha antagonist was restarted in the event of a relapse (DAS28>3.2). RESULTS The 21 patients had a mean age of 61 years, a mean disease duration of 11.3 years, and a mean remission duration at TNFalpha antagonist discontinuation of 19.2 months. The TNFalpha antagonist was infliximab in 2 patients, adalimumab in 5, and etanercept in 14; and 14 patients were taking a concomitant DMARD. The number of patients still in remission after TNFalpha antagonist discontinuation was 9/20 after 6 months and 5/20 after 12 months. Mean time to relapse was 14.7 weeks. While off TNFalpha antagonist therapy, 3 of the 5 relapse-free patients after 12 months were on DMARD therapy, compared to 11 of the 15 patients who relapsed. Compared to the 15 patients who relapsed, the 5 relapse-free patients had a longer time on TNFalpha antagonist therapy (56 months vs. 35 months, P=0.012) and a longer time in remission on TNFalpha antagonist therapy (35 months vs.14.5 months, P=0.04). The 15 patients who relapsed consistently achieved a remission after resuming TNFalpha antagonist therapy; the remission occurred within 2 months in 13 patients. CONCLUSION TNFalpha antagonist discontinuation in patients in remission of RA was followed by a relapse within 12 months in 75% of cases. Relapsing patients responded well to resumption of the same TNFalpha antagonist.

Hip osteoarthritis: short-term efficacy and safety of viscosupplementation by hylan G-F 20. An open-label study in 22 patients

UNLABELLED We studied the short-term safety and efficacy of intraarticular hylan G-F 20 (Synvisc) in patients with symptomatic hip osteoarthritis. METHODS In this open-label prospective study, patients who had hip osteoarthritis with a visual analog pain scale score greaterthan 40/100 and a Lequesne index greater than 6 received one or two intra-articular injections of hylan G-F 20 under fluoroscopic guidance. The patients were evaluated once a month. A response was defined as a 50% decrease in the Lequesne score after 1 month as compared to baseline. RESULTS Thirty injections were performed in 22 patients with a mean age of 54 years. The response rate was 50% (11/22) after the first injection. Five of the 11 patients who failed to respond to the first injection received a second injection on day 30; two had a response, yielding a cumulative response rate of 13/22. In the six patients followed up for more than 6 months, the improvement was sustained. Short-term safety was satisfactory, with a self-limited exacerbation of pain during the first few days in three patients but no infections or other side effects.

Insufficiency fracture of the sacrum revealing a pregnancy associated osteoporosis. First case report

Osteoporosis of pregnancy, usually responsible for spinal or femoral fracture,1 is rare as is insufficiency fracture of the sacrum, usually occurring in the elderly.2Magnetic resonance imaging (MRI) permitted during pregnancy, led us to diagnose an insufficiency fracture of the sacrum revealing a pregnancy associated osteoporosis, never previously reported to the best of our knowledge. Rheumatologists need to be aware of this new cause of pelvic pain during pregnancy. A 29 year old pregnant (seventh month) woman presented with a spontaneous acute claudication in conjunction with a left hyperalgesic buttock pain. Her past medical history showed: low back pain, since the second month of her pregnancy, relieved by rest and paracetamol; smoking (10 packet years) stopped at the sixth month of pregnancy; one spontaneous miscarriage at six months responsible for …

Erdheim-Chester disease: typical radiological bone features for a rare xanthogranulomatosis

A 55 year old man was admitted to the rheumatology department owing to inflammatory back pain (occurring at 4 00 am, not aggravated by movement) without sciatica, increasingly severe over two years and associated with asthenia and weight loss (10 kg). No abnormalities were found on physical examination, except for tenderness on palpation of the spinous processes of L5 and S1. There was no significant past medical history. Laboratory tests showed a mild inflammatory picture: erythrocyte sedimentation rate 25 mm/1st h (normal 5–15), C reactive protein 12 mg/l (normal 0–10), fibrinogen 5.1 g/l (normal 2–4). Protein electrophoresis, red and white blood cell count, glucose, renal, and liver function tests were normal. Chemical bone markers (urinary pyridinoline, alkaline phosphatase, osteocalcin, parathormone, 25-hydroxyvitamin D, serum calcium and phosphorus, and urinary calcium and phosphorus) were normal. Standard lumbar spine and pelvic radiographs were normal. Technetium-99m bone scintigraphy showed no abnormal uptake in the spine or skull but disclosed an increased peripheral uptake. A skeletal survey showed multiple mixed bone lesions with sclerotic areas surrounding smaller lytic foci. These roughly bilateral, symmetrical lesions involved the metaphyses and diaphyses of some long bones but spared the epiphyses. Bones affected were the femora, tibiae, radii, wrist, and tarsal bones (fig 1). Figure 1 Skeletal bone radiographs showed bilateral and symmetrical cortical osteosclerosis of the …

Step-down strategy of spacing TNF-blocker injections for established rheumatoid arthritis in remission: results of the multicentre non-inferiority randomised open-label controlled trial (STRASS: Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study)

Tumour necrosis factor (TNF)-blocker tapering has been proposed for patients with rheumatoid arthritis (RA) in remission. Objective The trial aims to compare the effect of progressive spacing of TNF-blocker injections (S-arm) to their maintenance (M-arm) for established patients with RA in remission. Methods The study was an 18-month equivalence trial which included patients receiving etanercept or adalimumab at stable dose for ≥1 year, patients in remission on 28-joint Disease Activity Score (DAS28) for ≥6 months and patients with stable joint damage. Patients were randomised into two arms: maintenance or injections spacing by 50% every 3 months up to complete stop. Spacing was reversed to the previous interval in case of relapse, and eventually reattempted after remission was reachieved. The primary outcome was the standardised difference of DAS28 slopes, based on a linear mixed-effects model (equivalence interval set at ±30%). Results 64 and 73 patients were included in the S-arm and M-arm, respectively, which was less than planned. In the S-arm, TNF blockers were stopped for 39.1%, only tapered for 35.9% and maintained full dose for 20.3%. The equivalence was not demonstrated with a standardised difference of 19% (95% CI −5% to 46%). Relapse was more common in the S-arm (76.6% vs 46.5%, p=0.0004). However, there was no difference in structural damage progression. Conclusions Tapering was not equivalent to maintenance strategy, resulting in more relapses without impacting structural damage progression. Further studies are needed to identify patients who could benefit from such a strategy associated with substantial cost savings. Trial registration number: ClinicalTrials.gov: NCT00780793; EudraCT identifier: 2007-004483-41.

Non–TNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With Insufficient Response to a First Anti-TNF Drug: A Randomized Clinical Trial

Importance One-third of patients with rheumatoid arthritis show inadequate response to tumor necrosis factor α (TNF-α) inhibitors; little guidance on choosing the next treatment exists. Objective To compare the efficacy of a non-TNF-targeted biologic (non-TNF) vs a second anti-TNF drug for patients with insufficient response to a TNF inhibitor. Design, Setting, and Participants A total of 300 patients (conducted between 2009-2012) with rheumatoid arthritis, with persistent disease activity (disease activity score in 28 joints-erythrocyte sedimentation rate [DAS28-ESR]  ≥ 3.2 [range, 0-9.3]) and an insufficient response to anti-TNF therapy were included in a 52-week multicenter, pragmatic, open-label randomized clinical trial. The final follow-up date was in August 2013. Interventions Patients were randomly assigned (1:1) to receive a non-TNF-targeted biologic agent or an anti-TNF that differed from their previous treatment. The choice of the biologic prescribed within each randomized group was left to the treating clinician. Main Outcomes and Measures The primary outcome was the proportion of patients with good or moderate response according to the European League Against Rheumatism (EULAR) scale at week 24. Secondary outcomes included the EULAR response at weeks 12 and 52; at weeks 12, 24, and 52; DAS28ESR, low disease activity (DAS28 ≤3.2), remission (DAS28 ≤2.6); serious adverse events; and serious infections. Results Of the 300 randomized patients (243 [83.2%] women; mean [SD] age, 57.1 [12.2] years; baseline DAS28-ESR, 5.1 [1.1]), 269 (89.7%) completed the study. At week 24, 101 of 146 patients (69%) in the non-TNF group and 76 (52%) in the second anti-TNF group achieved a good or moderate EULAR response (OR, 2.06; 95% CI, 1.27-3.37; P = .004, with imputation of missing data; absolute difference, 17.2%; 95% CI, 6.2% to 28.2%). The DAS28-ESR was lower in the non-TNF group than in the second anti-TNF group (mean difference adjusted for baseline differences, -0.43; 95% CI, -0.72 to -0.14; P = .004). At weeks 24 and 52, more patients in the non-TNF group vs the second anti-TNF group showed low disease activity (45% vs 28% at week 24; OR, 2.09; 95% CI, 1.27 to 3.43; P = .004 and 41% vs 23% at week 52; OR, 2.26; 95% CI, 1.33 to 3.86; P = .003). Conclusions and Relevance Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but with inadequate primary response, a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks than was the second anti-TNF medication. Trial Registration clinicaltrials.gov Identifier: NCT01000441.

The influence of the definition of patient global assessment in assessment of disease activity according to the Disease Activity Score (DAS28) in rheumatoid arthritis.

Objective. Patient global assessment (PGA) is one of the 4 items included in the Disease Activity Score (DAS28) for evaluation of activity of rheumatoid arthritis (RA). We studied the influence of the use of 3 different techniques of PGA on the assessment of disease activity. Methods. We evaluated 3 different DAS28 according to the technique of PGA in 108 patients with active RA before and after 12 weeks of etanercept therapy. Results. The reliability (intraclass coefficient of correlation) between screening and baseline was very high and similar for the 3 DAS28. The percentage of patients in the different states of disease (from remission to higher disease activity) and the sensitivity to change across the 3 DAS28 scales were very similar. Conclusion. The different techniques of collection of PGA to be included in the DAS calculation yield similar results. However, an accepted, unequivocal technique should be encouraged in order to reduce heterogeneity in scoring DAS among patients with RA.

Etanercept Compared to Intraarticular Corticosteroid Injection in Rheumatoid Arthritis: Double-blind, Randomized Pilot Study

Objective. To compare etanercept (anti-tumor necrosis factor-α) with intraarticular (IA) corticosteroid injections to treat rheumatoid arthritis (RA). Methods. Patients with RA who had persistent monoarthritis received etanercept or IA corticosteroid injections. Efficacy was compared at Weeks 4 and 24. Results. Thirty-four patients were included (8 dropped out). Mean age was 58.8 years. No difference between groups was found at Weeks 4 or 24, but both groups showed significant improvement at Weeks 4 and 24 compared to baseline. Conclusion. Etanercept and IA steroid injections resulted in significant improvement at Week 4 that persisted to Week 24. There was no significant difference in outcome between the groups.

Influenza and pneumococcal vaccine coverage in 584 patients taking biological therapy for chronic inflammatory joint: A retrospective study

OBJECTIVES To evaluate influenza and pneumococcal vaccine coverage in patients taking biological therapy for chronic inflammatory joint disease and to identify factors associated with the decision to administer these two vaccines. METHODS Retrospective cross-sectional questionnaire study of a cohort of 584 patients taking biological therapy for chronic inflammatory joint disease (rheumatoid arthritis or spondyloarthritis). We studied the influenza and pneumococcal vaccine coverage rates, information about these vaccines given to patients by the primary-care physician and rheumatologist, and reasons for not administering the vaccines. RESULTS Overall vaccine coverage rates were 44% for influenza and 62% for pneumococcus. Factors associated with being vaccinated were patient age, previous influenza vaccination, and patient information. Concern about adverse effects and absence of patient information by the primary-care physician and rheumatologist were associated with very low coverage rates. CONCLUSION This study showed insufficient vaccine coverage rates, particularly against influenza, in a population at high risk because of exposure to biological therapy. Patient information by healthcare professionals about influenza and pneumococcal vaccination has a major impact and should be renewed as often as possible.

Pleural amyloidosis as the first sign of IgD multiple myeloma

We describe a case of IgD myeloma with amyloid and plasmocytic pleural localisations. At the onset of the disease it mimicked rheumatoid arthritis, which can be the first presentation of both AL amyloidosis and multiple myeloma. Pleural effusion can happen first in IgD myeloma, but our observation is of interest in that it confirms the very rare possibility of pleural amyloid and plasmocytic localisations devoid of pleural effusion.