Do biologic drugs affect the need for and outcome of joint replacements in patients with rheumatoid arthritis? A register-based study.

OBJECTIVES: The aim was to study the incidence of joint replacements among biologic drug and disease-modifying anti-rheumatic drug (DMARD) users as well as to investigate the plausible effect of biologic treatment on survival of prostheses in patients with Rheumatoid arthritis (RA). METHODS: The study population comprised 2 cohorts of patients [Register of biologic treatment in Finland (ROB-FIN) and the Central Finland RA database] from 1999 to 2010. Records of joint replacements performed in the study population between 1980 and 2010 were retrieved from the Finnish Arthroplasty Register. Propensity score matching was used to equalize patient characteristics between biologics and DMARD users. The incidence rates of primary and revision operations were compared between the 2 treatment groups. Kaplan-Meier survival analysis was used to analyze prosthesis survival. RESULTS: Of the 2102 biologics and 2710 DMARD users identified from the registries, 1587 were included in both groups after the matching. Median follow-up times were 3.1 and 8.0 years, respectively. There were more primary operations per 100 patient years in the biologics (3.89, CI 95% 3.41-4.41) vs. DMARD (2.63, 2.35-2.94) group but slightly fewer revisions (0.65, 0.46-0.88 vs. 0.83, 0.68-1.01). Biologics users were more likely to receive a joint replacement to small joints (p < 0.001). The survival of the prostheses installed during or prior to follow-up was similar in both treatment groups. CONCLUSIONS: The use of biologic drugs did not reduce the need for joint replacement surgery in patients with a similar on-medication disease activity. Despite possibly lower rate of revisions among biologic users, the durability of prostheses was not improved.

Systematic review and meta-analysis of the efficacy and safety of existing TNF blocking agents in treatment of rheumatoid arthritis.

BACKGROUND AND OBJECTIVES: Five-tumour necrosis factor (TNF)-blockers (infliximab, etanercept, adalimumab, certolizumab pegol and golimumab) are available for treatment of rheumatoid arthritis. Only few clinical trials compare one TNF-blocker to another. Hence, a systematic review is required to indirectly compare the substances. The aim of our study is to estimate the efficacy and the safety of TNF-blockers in the treatment of rheumatoid arthritis (RA) and indirectly compare all five currently available blockers by combining the results from included randomized clinical trials (RCT). METHODS: A systematic literature review was conducted using databases including: MEDLINE, SCOPUS (including EMBASE), Cochrane library and electronic search alerts. Only articles reporting double-blind RCTs of TNF-blockers vs. placebo, with or without concomitant methotrexate (MTX), in treatment of RA were selected. Data collected were information of patients, interventions, controls, outcomes, study methods and eventual sources of bias. RESULTS: Forty-one articles reporting on 26 RCTs were included in the systematic review and meta-analysis. Five RCTs studied infliximab, seven etanercept, eight adalimumab, three golimumab and three certolizumab. TNF-blockers were more efficacious than placebo at all time points but were comparable to MTX. TNF-blocker and MTX combination was superior to either MTX or TNF-blocker alone. Increasing doses did not improve the efficacy. TNF-blockers were relatively safe compared to either MTX or placebo. CONCLUSIONS: No single substance clearly rose above others in efficacy, but the results of the safety analyses suggest that etanercept might be the safest alternative. Interestingly, MTX performs nearly identically considering both efficacy and safety aspects with a margin of costs.

Outcomes of switching anti-TNF drugs in rheumatoid arthritis--a study based on observational data from the Finnish Register of Biological Treatment (ROB-FIN).

The aim of this study was to assess, based on observational data from the Finnish Register of Biological Treatment, the outcomes of switching an initial tumor necrosis factor (TNF) blocker to another in the treatment of rheumatoid arthritis (RA). RA patients, who started biological therapy with a TNF blocker between May 1999 and April 2009 and who switched to another TNF blocker, were studied (n=479). The outcomes were assessed according to the reason for and type of the switch. Outcome assessments included American College of Rheumatology 50 responder index (ACR50) response at 3 months after the switch, treatment duration of the second TNF blocker, and swollen joint counts, CRP and DAS28 score at the 3 months, best and last observations of the first and second TNF blocker, respectively. In those who switched due to lack of effectiveness (LOE), the disease activity parameters fell significantly from baseline upon use of infliximab or adalimumab, but had increased prior to the switch. Switching to another TNF blocker (etanercept or adalimumab) restored the response initially achieved with the first TNF blocker. The disease activity parameters fell significantly from baseline upon use of etanercept, and were maintained but not further improved after switching to adalimumab. TNF blocker switching seemed to be most beneficial in secondary LOE (defined as loss of ACR50 response). In those who switched due to adverse events (AE) or other reasons, a similar degree of response as had been achieved with the first agent was also achieved and maintained with the second agent. The results suggest that a second TNF blocker can restore the response in cases of secondary LOE and maintain it after switching due to an AE.

Biological therapy for psoriatic arthritis in clinical practice: outcomes up to 2 years.

OBJECTIVE: To evaluate the performance of biological drugs in psoriatic arthritis (PsA) in a routine care setting, using the Finnish national register of biological treatment (ROB-FIN). METHODS: Patients with PsA who started therapy with infliximab or etanercept between June 2000 and February 2006 (n = 127) were followed for up to 24 months. Response was evaluated using American College of Rheumatology response criteria including individual measures. RESULTS: Significantly diminished values for swollen and tender joints, patient's global and pain assessments, doctor's global assessment of disease activity, erythrocyte sedimentation rate, C-reactive protein, and Health Assessment Questionnaire score were observed within 3 months after commencement of both infliximab and etanercept. Values remained significantly lower throughout the 24 months of followup. ACR20 response at 3 months was 79% (n = 22/28) for infliximab and 76% (n = 34/45) for etanercept. The first biological drug was discontinued in 16% due to lack of effectiveness and in 6% due to adverse events. CONCLUSION: Anti-tumor necrosis factor-α therapy, often combined with conventional disease-modifying antirheumatic drugs, appeared to have limited toxicity and persistent effectiveness for up to 2 years in a cohort of Finnish patients with severe peripheral PsA.

Dehydroepiandrosterone (DHEA) substitution treatment for severe fatigue in DHEA-deficient patients with primary Sjögren's syndrome.

OBJECTIVE: Primary Sjögren's syndrome (SS) is characterized by fatigue and low levels of serum dehydroepiandrosterone/dehydroepiandrosterone sulfate (DHEA/DHEAS). Our aim was to study whether SS patients with severe fatigue and low serum DHEAS values benefit from DHEA substitution (50 mg/day). METHODS: A multicenter, investigator-based, powered, randomized controlled clinical trial (crossover, washout design) using fatigue as the primary outcome measure was performed on patients with primary SS (n = 107) who had a general fatigue score > or =14 on the 20-item Multiple Fatigue Inventory (MFI-20), combined with age- and sex-adjusted serum DHEAS values below the mean. Fatigue was assessed using MFI-20 subscales, i.e., general fatigue, physical fatigue, mental fatigue, reduced motivation, and activity (scale 4-20), and with a visual analog scale (VAS; scale 0-100). RESULTS: In an intent-to-treat analysis, a 50-mg DHEA substitution dose and placebo similarly improved fatigue. All of the MFI-20 subscales and the fatigue VAS improved from the baseline levels as a result of treatment (P < 0.001), but with negligible differences between these 2 treatments. The mean between-treatment difference was -0.1 for general fatigue (the primary outcome measure), 0.0 for physical fatigue, 0.0 for mental fatigue, 0.0 for reduced motivation, 0.3 for reduced activity, and 2.2 for the fatigue VAS. None of these differences was statistically significant. CONCLUSION: Similar to earlier results using pharmacologic doses, substitution treatment with 50 mg of DHEA in DHEA-deficient and severely tired primary SS patients does not help against fatigue better than placebo. This may relate to the prohormone nature of DHEA and its recently described defective intracrine tissue-specific conversion to active sex steroids in SS.

New operative technique for treatment of arthroscopically-confirmed injury to the scapholunate ligament by volar capsuloplasty augmented with a free tendon graft.

We report how scapholunate (SL) lesions found during arthroscopy were treated using a new palmar operation based on the use of a tendon loop formed using the palmaris longus tendon, with promising preliminary results. Scapholunate instability induced by hyperextension injury was diagnosed and graded arthroscopically. Volar capsuloplasty was then done by free tendon graft in the same session in 31 patients with grades II-IV scapholunate instability. Half of the patients operated on had a normal range of movement, and all except one had flexion-extension of at least 75% of the normal. Half of the patients had no pain or limitations of the use of the wrist, and although half the patients had some pain on exertion, not one had severe pain. These results are comparable to, or even better than, those reported using other methods of repair. The combined procedure saves money, diminishes the total recuperation time and, as autologous tissues are used for the repair, secondary operations for removal of the implant are unnecessary. This method seems to be a useful adjunct to the types of operative treatment available, although it is apparently not suitable in static grade IV SL instability.

Correction of chronic lunotriquetral instability using extensor retinacular split: a retrospective study of 26 patients.

Arthroscopy offers a welcome and reliable supplement to the current tool set for the diagnosis of lunotriquetral (LT) instability. This study reports the findings of LT-lesions during arthroscopy and the clinical results obtained after using dorsal stabilisation in its surgical management using extensor retinacular split. LT-instability of grade I-III was diagnosed in 26 patients. Imaging results were normal, Reagan's ballottement and Watson tests were positive in 47% and 79%, respectively. After arthroscopic diagnosis, the procedure was immediately continued with an open repair utilising an 8-10 mm wide and radial-based extensor retinacular split for dorsal capsular reinforcement. At 39 months (range: 14 to 84) follow-up, 64% had no or only occasional mild pain and 36% had pain with overuse or lifting. Overall scoring encompassing pain, patient satisfaction, range of motion and grip strength, was excellent in 24% and good in 64%. Only three patients had fair results, one after a further injury leading to distal radio-ulnar joint (DRUJ) instability, and two with concurrent DRUJ-stabilisation. One further patient required a secondary procedure. Arthroscopy seems to allow accurate diagnosis of LT-instability and can be continued in the same session using a straightforward reconstruction procedure providing satisfactory results.