Current Evidence for the Management of Rheumatoid Arthritis


monotherapy at two years. Results from the multicentre single-blinded BeSt trial (508 RA patients with less than two years of symptoms) have also shown a more rapid clinical response and a better radiographic outcome in the two initial intensive treatment groups, a triple step-down strategy with MTX, SSZ, and high-dose prednisone (group 3), and initial combination therapy with IFX + MTX (group 4), than those receiving sequential monotherapy (group 1) or step-up combination therapy (group 2), at two years. After four years, less radiographic progression was seen in those initially treated with IFX compared with the other groups. Fifty-six per cent of patients in this group were able to successfully stop IFX compared with 15% in the other groups at two years, suggesting that, by achieving remission earlier, patients may require less treatment later on in the disease course.55


Despite the many different strategic approaches used, an SLR analysing the various treatment strategies found that it was not possible to recommend one single optimal medication sequence.56 This was partly due to a lack of appropriate comparisons across the various studies and also due to the use of prednisolone in many treatment strategies. For now, initial treatment choices may therefore need to be individualised, taking into account various clinical and laboratory prognostic markers.


Tight Control


A considerable evidence base has illustrated, apart from initial drug choice, the importance of adherence to the practice of close monitoring of disease activity with titration of pharmacotherapy.


In the Tight Control of RA (TICORA) study,57 which compared an


intensive treatment strategy (monthly examination and DMARD therapy escalation according to a predefined strategy if the DAS44 was above 2.4) or routine care (three-monthly examination without formal assessment and therapy adjustment according to clinical judgement), remission rates were significantly higher and radiographic damage less in the intensively treated group compared with the control group after 18 months of follow-up. Notably, however, more intra-articular steroids were used in this group to achieve this pre-defined target.


The Computer-Assisted Management of Early RA (CAMERA) trial58 similarly showed intensive treatment and monitoring using a computer-assisted programme to be more beneficial than routine care. At two years, sustained remission for at least three months was greater in the intensively managed than in the routine care group (50 versus 37%; p<0.03). Patients in the latter group also used less non- steroidal anti-inflammatory drugs. Results of the BeSt study showed good clinical outcomes in all patient groups and sustained clinical and functional benefit for up to four years, reinforcing the importance of early intervention and tight control in the treatment of RA.59


Further studies and a recent review of the literature have also shown better outcomes where intensive care was based on regular monitoring of disease activity and treatment to target.56,60,61


Results of


the trials were consistent in showing significant benefits for intensive management on clinical outcome, physical function and structural damage, regardless of the method used. Regular monitoring of disease activity and adverse events, therefore, should guide decisions on choice and changes in treatment strategies. The majority of the studies used composite outcome measures for


EUROPEAN MUSCULOSKELETAL REVIEW


Table 2: The 2010 American College of Rheumatology/European League against Rheumatism Classification Criteria for Rheumatoid Arthritis64


Target Population (Who Should Be Tested?) 1.


2.


Patients with at least one swollen joint with definite clinical synovitis (swelling)


Synovitis is not better explained by another disease Differential diagnoses differ in patients with different presentations but may include conditions such as systemic lupus erythematosus, psoriatic arthritis and gout. If unclear about the relevant differentials, an expert rheumatologist should be consulted


Classification Criteria for Rheumatoid Arthritis* A. Joint Involvementa 1 largeb


joint


2–10 large joints 1–3 smallc


joints (with or without involvement of large joints)


4–10 small joints (with or without involvement of large joints) >10 jointsd


(at least one small joint)


B. Serologye** Negative RF AND negative ACPA Low positive RF OR low positive ACPA High positive RF OR high positive ACPA


C. Acute phase Reactantsf** Normal CRP AND normal ESR Abnormal CRP OR abnormal ESR


D. Duration of symptomsg <6 weeks ≥6 weeks


Score-based algorithm: add score of categories A–D. A score of ≥6/10 is needed for a definite classification of a patient with rheumatoid arthritis; a


* Joint involvement refers to any


joint swollen or tender on examination, which may be confirmed by imaging evidence of synovitis. Distal interphalangeal (DIP) joints, first carpometacarpal (CMC) joint and first metatarsophalangeal (MTP) joint are excluded from assessment. Categories of joint distribution are classified according to the location and number of the joints involved, with


placement into the highest category possible based on the pattern of joint involvement; b


Large joints refer to shoulders, elbows, hips, knees and ankles; c


wrists, metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, thumb interphalangeal (IP) joints and metatarsophalangeal (MTP) joints 2–5; d


Small joints refer to the In this category, at


least one of the joints involved must be a small joint; the other joints can include any combination of large and additional small joints, as well as other joints not specifically listed elsewhere (e.g. temporomandibular, acromioclavicular and sternoclavicular joints); e


refers to international unit (IU) values that are less than or equal to upper limit of normal (ULN) for the laboratory and assay. Low titre refers to IU values >ULN but ≤3x ULN for laboratory and assay. High titre positive means >3x ULN for the lab and assay. Where RF is only available as positive or negative, positive results should be scored as ‘low positive’ for RF; **


At least one test result is needed for classification; f


local laboratory standards. (Other causes for elevated acute phase reactants should be excluded.); g


Negative


0 1 2 3 5


0 2 3


0 1


0 1


Normal/abnormal is determined by


Duration of symptoms refers to patient self-report of the duration of signs or symptoms of synovitis (e.g. pain, swelling, tenderness) of joints that are clinically involved at the time of assessment, regardless of treatment status. RF = rheumatoid factor; ACPA = anti-citrullinated protein/peptide antibodies; ESR = erythrocyte sedimentation rate; CRP = C-reactive protein.


monitoring of disease activity (including tender and swollen joint counts, patient and physician global assessments and inflammatory markers). Monitoring of radiographic progression and functional assessments (e.g. the Stanford Health Assessment Questionnaire) complement the clinical assessment. The concept of setting a target (similar to the approach in the control of hypertension and diabetes) was recently formally addressed by a task force of rheumatologists and a patient. A set of 10 recommendations, based on an SLR and expert opinion, to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes in RA, was developed. The treat-to-target activity encompassed the concept of early treatment and formalised the need for frequent monitoring using disease activity measures with adjustment/titration of pharmacotherapy in order to achieve the goal of remission or, alternatively, at least LDAS.1


27


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68