› Basic Info

› FAQ

The Breakthrough in the Treatment of Rheumatoid Factor Positive Rheumatoid Arthritis by the John Darmawan Protocol (JDP).

Remission under intravenous and oral therapy is achieved after 2-4 months since initiation of the JDP

Remission sustained by oral drugs is achieved after 5.5-7.5 months since initiation of the JDP

Remission without drug is obtained after 3.5-4.5 years since initiation of the JDP

Rheumatoid Arthritis (RA) is an autoimmune disease with unknown cause, but with various manifestations in particular peripheral joints. When the Rheumatoid Factor (RF+) is positive the acronym is RF+ RA. The high activity of the disease and consequent disability and subsequent deformity of RF+ RA are aggressively progressive. Without adequate suppression of the autoimmune inflammation in RF+ RA the ultimate outcome of the disease is early death.

Remission of RF+ RA is defined when:
- signs and symptoms are:
1. mean swollen and tender joint count are < 1
2. normal CRP (< 3 mg%)
3. mean ESR < 25 mm/1 hour (men < 15 mm) Westergren
4. mean Patient Global Assessment > 4 (1-5)
5. mean Visual Analog pain Scale < 10 (0-100)
- functional impairment
mean ARA Functional Class < 2 (0-4)

Remission under intravenous and oral therapy is achieved after 2-4 months since initiation with the JDP. The JDP is a Step-down Bridge Protocol of Intravenous and Oral Combination of 6 Immunosuppressants. It is applied in patients with RF+ RA with Erythrocytes Sedimentation Rate (ESR) of more than 40 mm per hour Westergren and CRP of more than 3 mg%. Rheumatoid Factor Negative RA (RF- RA) may not require the JDP for therapy.

The principle of the JDP is to induce Remission in the shortest possible period of time, before grade 2 or more erosion is seen on X-ray film. By intensive daily administration of intravenous combination of 4 Immunosuppressants Remission is achieved. The 4 intravenous Immunosuppressants comprise Cyclophosphamide, 5-Flurouracil, Methylprednisolone, and Methotrexate.

Remission under intravenous and oral therapy is acquired after 2-4 months since initiation of the JDP. The Remission achieved is sustained by oral combination of 2-3 Immunosuppressants, while the intravenous therapy is tapered off after 5.5-7.5 months since initiation of treatment. This is called Remission with oral Drugs. The oral therapy is initiated together with the intravenous therapy for initial loading. The oral therapy will attain a serum level effective in maintaining ESR of less 20 mm per hour when the intravenous therapy is tapered off.

The oral therapy consists of Mycophenolate Mofetil and Methotrexate/Cyclosporine and must be continued for at least 2 years. After 2 years in Remission, the oral drugs are tapered off over a period of 1 year. If no flare occurs after oral drugs are tapered off then Remission without Drug is achieved in RF+ RA after 3.5-4.5 years since initiation of the JDP.

Flare is defined when the arthritis re-appears in 1 Or more joints and the ESR becomes abnormal (more than 25 mm per hour). Early (within 1 week) Flare of RF+_RA must be immediately suppressed by reinstitution of the JDP to maintain short, medium, and
long-term Remission.

To induce Remission under intravenous and oral therapy, the JDP must be administered daily 5 X weekly until ESR drops to less than 40 mm per hour. This is to avoid weekly cumulative dose induced adverse effects.

After ESR dropped to less than 40, 30, and 25 mm/hour (men < 30, < 20, and < 15 mm), the IV sessions are tapered to 3X, 2X, and 1X weekly respectively. When ESR is < 20 (women) or < 10 mm (men) disease is controlled. When disease is controlled, the IV session is tapered to once fortnightly (in conjunction with switching IV to once weekly oral equivalent dosage of Methotrexate), 4-weekly, 8-weekly and then terminated to Remission with oral Drugs.

The variable schedules in achieving various types of Remisions
 

1. Induction of Remission over 1-2 months after initiation by the JDP
2. Reduction of weekly IV sessions over 1-2 months
3. Remission achieved after 2-4 months
4. Tapering off intravenous sessions after 3.5 - 5.5 months since initiation of the JDP
5. Remission with oral Drugs after 5.5-7.5 months since initiation of the JDp
6. Consolidation of Remission with oral Drugs over 2 years
7. One year taperinf off oral drugs
8. Remission without Drug achieved after 3.5 - 4.5 years including Radiological
   Remission since initiation of the JDP.

Remission without drug is not a cure for RF+ RA. Flare can be induced by mental and physical stress, a viral infection, pregnancy, and after delivery of a baby.

The adverse effects of the 6 Immunosuppressants are listed in a leaflet in the drug package. Neupogen, Recormon, and combination of Epineprine+Methylprednisolone can overcome blood toxicities in a relative short period of time. Gastrointestinal toxicities such as anorexia, nausea, vomiting, diarrhea, including allergy can be treated and prevented by Kytril, spasmolytics, and anti-allergics.

The dreaded blood toxicities of low white blood cell, red cell, and thrombocytes count are avoided by daily intravenous low dosages of the immunosuppressants and low total frequency of administration, limited weekly and total cumulative dosages, and limited period of exposure.

Total Immunosuppressant-naivety is defined when the patient has never been treated with Cyclophosphamide, 5-Flurorouracil, Methylprednisolone, Methotrexate, and Mycophenolate Mofetil, and Cyclosporine. Partial Immunosuppressant-naivety is defined when the patient has been treated with several of the 6 Immunosuppressants. Total Immunosuppressant non-naivety is defined when the patient has been treated previously with all the 6 Immunosuppressants for example when a flare occurs. These naivety and non-naivety have implication for the outcome of RF+ RA by the JDP.

Cyclophosphamide, 5-Fluorouracil, and Methylprednisolone are not given by oral route because of:

Intravenous	versus	Oral administration
Faster efficacy Maximum efficacy Effect lasts longer Minimum adverse effects		Slower efficacy Minimum efficacy Effect last shorter Maximum adverse effects

Hematological adverse effects are very rarely encountered, but mild gastrointestinal ones oocur in 25% of the patients treated with the JDP. These can be easily overcome Or prevented.

 

 

  Email This Page   Print This Page