Rheumatoid Arthritis Treatment in Asia
General Treatment Strategy
The goal of treatment for RA is to achieve sustained disease remission or low disease activity. treatment should be initiated as soon as RA is diagnosed, and the treatment plan should be decided jointly by the physician and the patient after communication.
The choice of treatment plan should be based on disease activity and the presence of adverse prognostic factors and co-morbidities. Poor prognostic factors include positive rheumatoid factor (RF) or anti-citrullinated protein antibodies, elevated blood sedimentation or C-reactive protein (CRP), and imaging evidence of joint erosion or progressive joint destruction (2B).
All patients should be evaluated at follow-up for extra-articular manifestations of disease, co-morbidities, infections (e.g., tuberculosis and hepatitis), information on vaccination status and special conditions (e.g., pregnancy, breastfeeding). Screen for osteoporosis and cardiovascular disease. (2B)
Glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs) may be reduced to discontinued if remission persists for 6 months.
If remission is maintained for 6 to 12 months after discontinuation of NSAIDs, glucocorticoids, and biologic disease-modifying antirheumatic drugs (bDMARD), synthetic DMARDs (cDMARD) may be tapered cautiously by the physician after discussion with the patient (4D).
About NSAID
NSAIDs do not have a disease-modifying effect on RA progression (1A); non-selective NSAIDs and cyclooxygenase-2 (COX-2) inhibitors should be used at the lowest effective dose and for the shortest time allowed by the disease (4D); non-selective NSAIDs and COX-2 inhibitors should be evaluated for gastrointestinal, cardiovascular (1A) and renal function (2B) prior to treatment. Glucocorticoids
Oral glucocorticoid monotherapy is not recommended for RA (4D); to control active RA, oral glucocorticoids can be used in combination with cDMARD (1A); in early RA, the addition of low-dose glucocorticoids (prednisolone ≤7.5 mg/d) may delay imaging progression (1A); glucocorticoids should be used at the lowest dose possible and tapered as soon as the disease allows (4D).
Synthetic disease-modifying antirheumatic drugs (cDMARD)
cDMARD monotherapy or combination therapy should be started as soon as RA is diagnosed (1A).
Methotrexate (MTX) is the preferred cDMARD for RA and is considered the “anchor drug” (1A); for those who cannot tolerate MTX, other cDMARD treatments are available, such as leflunomide, salazosulfapyridine, and hydroxychloroquine as first-line options (1A), and in some Asia-Pacific countries, buspiramine, Elamod, cyclosporine, azathioprine, injectable gold preparations, or tacrolimus (1B).
Complete blood cytometric analysis, liver and renal function, viral hepatitis serology and chest radiograph should be performed before MTX treatment (2B).
Active RA, especially with poor prognostic factors, should be treated with a combination of cDMARD (1B); if MTX is not contraindicated, MTX should be used as an anchor drug for combination therapy (1A); triple therapy with cDMARD will be an effective option for patients who do not achieve complete remission with MTX monotherapy (1B).
The disease should be evaluated every 1 to 3 months after starting treatment or changing the regimen until complete remission or low activity (1A); when the disease is in remission or low disease activity, follow-up can be performed every 3 to 6 months (4D).
Failure to achieve disease remission or low disease activity after 6 months of combined therapy with two standard cDMARDs at appropriate doses is considered a failure of cDMARD therapy (1A); one of the drugs considered a failure of cDMARD therapy must be MTX, unless MTX is contraindicated (1A).
Biologic disease-modifying antirheumatic drugs (bDMARD)
When cDMARD therapy is inadequate or intolerant, bDMARD therapy is available. (1A)
bDMARD may be used early in those with active disease and poor prognostic factors or when cDMARD cannot be used.(4D)
Information should be obtained on the presence of active or presenting infections, co-morbidities, vaccinations, pregnancy and possible contraindications before treatment with bDMARD (1A); screening for tuberculosis, hepatitis B and C should be performed before bDMARD treatment.
Conditions in which bDMARD should be avoided include: acute and chronic infections, including joint infections within the past 12 months; solid or hematologic tumors (except basal cell carcinoma treated and in remission for more than 5 years); precancerous lesions; demyelinating lesions; severe cardiac insufficiency (FC III or IV); pregnancy and lactation; and low gammaglobulin or immunosuppressed individuals (low CD4 and CD8 counts). (3-4, C-D)
Hepatitis virus vaccination at least 4 weeks prior to bDMARD treatment. (3-4, C-D)
bDMARD is more effective in combination with MTX therapy (1A); if MTX is contraindicated or intolerant, other cDMARD should be combined (1A).
Options for bDMARD include tumor necrosis factor-α (TNF-α) inhibitors, abciximab, rituximab, and tolimumab (1A); 6 months of treatment with one bDMARD without remission may lead to conversion to another bDMARD (3C); dose reduction may be considered when remission is achieved (1A); more than 12 months of remission may lead to consideration of discontinuation of bDMARD (2B)
Use of bDMARD in special cases
TB screening is recommended prior to TB bDMARD treatment (2B); all potentially TB-infected patients should receive prophylactic anti-TB treatment (2B); active TB should be considered only after adequate treatment with bDMARD (3C).
Viral hepatitis bDMARD treatment should be preceded by screening for hepatitis B and C (4D); bDMARD should be avoided in patients with active or untreated chronic hepatitis B and active hepatitis C.
Other active infections are contraindications to bDMARD therapy (1A); when coinfection is clinically suspected, bDMARD therapy should be discontinued and appropriate consultation should be performed (1A).
When a comorbid tumor is suspected, a patient-specific analysis should be made and the decision should be discussed with the oncologist and the patient (4D); when faced with elective larger surgery, bDMARD should be discontinued for 2 to 4 half-lives prior to surgery (2B).
Pregnancy and breastfeeding should be avoided during bDMARD treatment, and contraception is strongly recommended for women of childbearing age (4D).
Vaccination should be administered at least 4 weeks prior to bDMARD treatment and live or attenuated vaccines are absolutely contraindicated during treatment.
Conference presentation on RA treatment
Prof. Zhanguo Li from Peking University People’s Hospital pointed out that RA is one of the important diseases causing disability in China, and the current remission rate of RA is far from satisfactory, and there are still irregularities in treatment. Prof. Li emphasized that in daily medical practice, patients should be treated early, combined with intensive treatment and individualized treatment strategies according to RA treatment guidelines or recommendations. Early treatment has a significantly better prognosis than delayed treatment. cDMARD combination or combination of cDMARD and bDMARD are better than monotherapy in slowing the progression of joint erosion.
Prof. Li noted that in a recent study comparing the efficacy of triple therapy with MTX combined with salazosulfapyridine and hydroxychloroquine to that of MTX combined with the biologic etanercept, there was no difference in the remission rate of the 28 joint disease activity (DSA28) score between the two groups of patients.
Patients who are not responding to TNF-α inhibitors can be treated with interleukin (IL)-6 inhibitors (tolimumab) and JAK-3 inhibitors (tofacitinib). In addition, the treatment of RA patients should be individualized, taking into account their co-morbidities and comorbidities, with the goal of achieving complete disease remission or low disease activity.
Biosimilars are generic versions of original biological drugs, which are attractive because of their low cost, but the manufacturing process is complex, and minor modifications may result in significant changes in the biological activity and immunogenicity of the drug, said Professor RHanda, an Indian academic. Unlike chemically synthesized drugs, biosimilars require more extensive preclinical physicochemical and biological characterization data to verify their bioequivalence.
The European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) already have processes in place to approve biosimilars. However, the feasibility or (and) desirability of interchangeability between biosimilars and originator biologic drugs remains to be investigated.
About RA treatment
Matsubara (TMatsubara) et al. reported the results of baricitinib (a new oral JAK1/JAK2 inhibitor) for the treatment of RA patients with inadequate response to MTX therapy in the Japanese population. This was a double-blind phase II study in which 145 patients were randomized to the baricitinib 4mg, 8mg, and placebo groups, with the results being that at 12 weeks of treatment, 67% and 88% of patients in the 4mg and 8mg groups met the American College of Rheumatology (ACR) improvement criteria of 20% (ACR20), significantly higher than the placebo group (30%), and DAS28-CRP The DAS28-CRP, the Brief Disease Activity Index (SDAI) and the Modified Health Assessment Questionnaire (HAQ-DI) scores were also better than those of the placebo group. The incidence of adverse events in the treatment group was similar to that of placebo and was mild, with no opportunistic infections or deaths.
Russian YAtrushkevich et al. reported similarities and differences in patients with RA with and without rheumatoid nodules. Namely, DSA28 was similar in both groups, but extra-articular manifestations of lymph node enlargement (9.4%), iridocyclitis (2.4%), polypoidal peripheral neuropathy (3.5%) and cutaneous vasculitis (8.2%) were more common in patients with subcutaneous nodules, and higher RF titers, low IgG levels and fewer CD3+ peripheral blood lymphocytes (PBL), and non-specific inflammation was more prominent in those without rheumatoid nodules (e.g., fever, weight loss, and malnutrition).