Disease Activity Scores

The TNF -308 polymorphism may be predictive of an individual patient s response to INF. In one study, 59 RA patients treated with INF after genotyping were classified into homozygotes for the TNF -308A allele (A/A 1.7%), heterozygotes (A/G 22%), and wild-type (G/G 76.3%) carriers of the allele. After 22 weeks of treatment with INF, the disease activity score (DAS a standardized measure of disease activity in RA) was used to assess response to INF. Patients without the A allele (81%) compared to patients with the A allele (42%) had a better response to INF as demonstrated by an improvement in the DAS (p 0.0009). Thus, this study suggested that RA patients who are carriers of the TNF=-30S G allele may have a more favorable response to INF (62). 

NSAID-refractory-AS is defined when after treatment with at least 2 different NS AID over a period of at least 2 months, ASAS 20 is not obtained, and ESR, CRP, and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score do not improve, or worsens versus baseline. Indications for therapy with SBC-5-IMNs are in NSAID-refractory AS with ESR > 40 mm and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) > 4. Less than 5% of patients with NSAID-refractory AS in the community at large fulfill these conditions. Remission is defined when ESR and VAS have declined to <10 mm (men <5 mm) and the disease activity scores are <1 (scale 0-10). Remission with oral drugs is defined when remission is maintained with oral drugs for at least 2 years. Remission without drugs is defined when remission without drugs is sustained without relapse for at least 2 years. 

Rheumatoid arthritis Multicenter experience 24 weeks Leflunomide 100 mg/day for 3 days, then 20 mg/day (n = 969) 191 withdrawn (107 adverse events, 26 lack of efficacy, 58 other reasons) 24% good and 45% moderate responses on the disease activity score, and 61%, 34%, and 9.6% achieved American College of Rheumatology 20, 50, and 70 response rates (19)... 

In a crossover study, 66 patients took 50 mg doxycychne or placebo twice a day for 12, 24, or 36 weeks (23). Patients assessments, swollen and tender joint counts, duration of morning stiffness, erythrocyte sedimentation rate, and the so-called modified disease activity score (25)... 

Prevoo ML, van t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995 38(l) 44-8. 

Elevated serum levels (3- to 5-fold) of MMP-3 have been demonstrated in patients with systemic lupus erythematosus, the prototype autoimmune disease, as compared to healthy controls. Contrary to anticipated results, serial measurements of MMP-3 in patients with SEE did not correlate with fluctuation in disease activity scores (Z12). Similar results were later reported by Keyszer et al. (K4). These data are consistent with the concept that MMP-3 is more related to the later tissue repair aspect, rather than to the initiating tissue injury process in SEE (Z12). If this assumption is correct, the use of MMP-inhibitory drugs may prove to be detrimental in diseases in which the... 

Observational studies Leflunomide has been evaluated in a prospective, non-interventional study in 334 adults with rheumatoid arthritis [61 ]. Disease activity score in 28 joints (DAS28) response was 72% at week 12 and 85% at week 24 25% achieved clinical remission. Adverse events were... 

Drug-drug iuteractious Allopurinol Treatment with allopurinol, a xanthine oxidase inhibitor, shifts metabolism towards higher thioguanine concentrations, reduces aminotransferase activities, and improves disease activity scores. In 41 patients with adverse reactions to full-dose thiopurines (25 with non-hepatic reactions and 16 with hepatic reactions), a combination of allopurinol with reduced-dose thiopurine bypassed many adverse drug reactions [173 ]. Remissions were achieved in 32 patients with a median follow-up of 41 (range 0.5-400) weeks. Patients who did not respond to combination therapy tended to fail early with the same adverse reaction. 

Fig. 1. Pouchitis Disease Activity Index (PDAI) score changes before and after antibiotic therapy in patients with chronic, treatment-resistant pouchitis (from Gionchetti et al. [50]).

The underlying rationale for early application of SBC-5-IMNs in LN is that once renal damage occurs, progressive damage will follow if the disease activity remains high (Systemic Lupus Activity Measure or SLAM score > 4). Indications for therapy with SBC-5-IMNs in DMARD-Refractory LN (DR-LN) include ... 

The use of cytokine antagonists (monoclonal antibodies to cytokines) used in the management of rheumatoid arthritis and Crohn s disease has some beneficial effect on Graves orbitopathy. A recent stndy of 10 patients with mild to moderately severe Graves orbitopathy showed that the administration of etanercept, an antitrunor necrosis fector drug (25 mg a week for 3 months) was associated with a significant improvement of the clinical activity score and ophthalmopathy index in approximately 60% of patients. 

In the 1980s, studies with EAE, an animal model mimicking MS, indicated that interferon y (IFN y) was effective in treating that disease and a trial was initiated to evaluate its potential benefit in human MS. Rather than showing efficacy, in 1987, use of IFNy as a therapy in MS patients caused an increase in clinical exacerbations and forced the clinical trial to terminate early (Panitch et al., 1987). Associated study of IFNy in 20 MS patients indicates increased concentrations of IFNy and TNFa precede the observation of clinical defects (Beck et al., 1988). An evaluation of primary RR-MS patient lymphocytes using flow cytometry supports a correlation between EDSS scores and IFNy secretion (Petereit et al, 2000). Intracellular cytokine immuno-staining of anti CD8-I- T cells reveals a correlation with IFNy and disease phase but not disease activity (Becher et al., 1999). What initially seemed efficacious in the EAE animal model, not only did not decrease MS symptoms but is now felt to be a marker of active inflammatory disease. 

The ratios of TIMP-1 MMP-1 and TIMP-LMMP-3 in blood have been reported to be significantly lower in patients with rheumatoid arthritis versus patients with nonrheumatoid arthritis (CIO). In rheumatoid arthritis patients, serum C-reactive protein correlated with MMP-3 and TIMP-1 levels, but not with MMP-1 levels. The number of erosions noted on X-rays correlated with baseline levels of MMP-3, but not TIMP-1. Cunnane et al. (CIO) postulated that treatment which inhibits the production and activation of MMP-1 may preferentially limit the formation of new joint erosions and improve the clinical outcome of patients with rheumatoid arthritis. In contrast to circulating levels of MMP-1, Keyszer et al. reported that MMPrTIMP complexes in blood correlate with rheumatoid activity scores (modified Lansbury Index and Keitel Function Index) in rheumatoid arthritis nonetheless, this relationship to disease activity was weaker than that of MMP-3 or C-reactive protein (K4). 

Arthritis clinical score and measurement of paw thickness are the basic measurements of disease activity. 

Stone JH, Hoffinan GS, Merkel PA, et al. A disease-specific activity index for Wegener s granulomatosis modification of the Birmingham Vasculitis Activity Score. International Network for the Study of the Systemic Vasculitides (INSSYS). Arthritis Rheum 2001 44(4) 912-920. 

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